2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Parkinson-Disease

Single photon emission computed tomography (SPECT) with Ioflupane I123 injection (DaTscan™) was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. While brain SPECT imaging using DaTscan is a covered service under Medicare policy, there is a lack of consensus on its role in routine clinical practice in the US. Areas covered: To address this issue, an expert group of US-based movement disorders neurologists convened to discuss the clinical utility of DaTscan in movement disorders practices within the US. The group identified and discussed routine clinical scenarios where imaging with DaTscan can provide useful information that may impact management and/or clarify clinical diagnoses. This paper summarizes a consensus reached by the expert group at this meeting. Expert commentary: The major utility of DaTscan imaging is the assistance it provides in distinguishing between nigrostriatal dopaminergic degeneration and non-nigrostriatal degeneration in patients displaying equivocal signs and symptoms of parkinsonism.

Topics: Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Humans; Nortropanes; Parkinson Disease; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon

Differentiating idiopathic Parkinson's disease from secondary parkinsonian syndromes is crucial since their management and prognosis differ considerably. Functional imaging of the dopaminergic pathway by means of [¹²³I]FP-CIT SPECT (DaTSCAN) might be useful in this regard, but its role is still controversial. The accuracy of DaTSCAN in the differential diagnosis between Parkinson's disease and vascular or drug-induced parkinsonism was therefore systematically reviewed.. MEDLINE and CENTRAL were searched for studies aiming to determine accuracy measures (sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism.. Five studies were included. Pooled accuracy measures in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism were relatively high, with sensitivity and specificity values above 85% and 80%, respectively.. DaTSCAN might accurately differentiate between early Parkinson's disease and secondary parkinsonian conditions, namely vascular or drug-induced, in patients with clinically unclear parkinsonism. However, all the studies reviewed here show several methodological limits, which prevent definitive conclusions on the role of DaTSCAN being drawn in this context. Further studies are needed to confirm our results and definitely evaluate the utility of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism.

Topics: Aged; Diagnosis, Differential; Humans; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

This review article is focused upon the most recent biomarker studies of Parkinson's disease. It provides an update on promising areas of biomarker research in a rapidly expanding field, and discusses future directions that might lead to successful development of Parkinson's disease biomarkers.. Studies of molecular-genetic and biochemical biomarkers of Parkinson's disease have not only targeted hypothesis-driven measures of specific substrates involved in processes such as protein misprocessing, but also have made use of sophisticated analyses such as transcriptomic, proteomic, and metabolomic approaches. Whereas none of these are yet established as Parkinson's disease biomarkers, brain imaging using the 123I-ioflupane ligand with single-photon emission computed tomography was recently approved in the United States to aid in Parkinson's disease diagnosis, and research on other imaging modalities is ongoing. Neurophysiological tests are also being adapted for biomarker research, and we review recent promising data.. The search for effective biomarkers for diagnosis and surveillance of Parkinson's disease continues. A battery of biomarkers comprising different modalities might be required to address clinical needs in this complex disorder. Critically, collaborative efforts including centralized tissue repository and clinical research infrastructure that are being organized will advance this field further.

Topics: alpha-Synuclein; Animals; Biomarkers; Dementia; Humans; MicroRNAs; Neurophysiology; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

Functional imaging is a tool that has been long restricted to research programs. However, the availability of ¹²³I-Ioflupane SPECT imaging has developed its' clinical utilization with a risk of misuse. There is room for improvement for the differential diagnosis between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes and the measure of brain glucose metabolism with PET might fill this gap in the future. Conversely, functional imaging is still a major tool for the evaluation of new experimental therapeutic strategies in PD, especially for those aiming at restoring or protecting striatal dopaminergic innervation.

Topics: Antiparkinson Agents; Brain Chemistry; Diagnosis, Differential; Dihydroxyphenylalanine; Dopamine Agents; Glucose; Humans; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, differentiating IPD from essential tremor or other parkinsonian syndromes solely by clinical examination can be challenging in some cases, especially in the early stage of the disease. The introduction of new isotopic functional imaging techniques, and more specifically the labelling of dopamine transporter derivatives, has improved the understanding and early detection of some diseases affecting the basal ganglia. Iodine-123-FP-CIT (DaTSCAN), a (presynaptic) dopamine transporter analogue for nuclear medicine imaging, has recently been introduced for the non-invasive differential diagnosis between IPD and essential tremor or secondary (e.g. drug-related) parkinsonian syndromes. DaTSCAN scintigraphy has also demonstrated some usefulness in the evaluation of other neurodegenerative parkinsonian syndromes such as Lewy-body dementia or multiple system atrophy. For this latter however, the DaTSCAN has to be combined with a second scintigraphy, imaging the post-synaptic dopaminergic receptors, such as the D2-ligand 123I-iodobenzamide. Combining DaTSCAN scintigraphy to a functional study of the brain cortical activity using a brain perfusion scintigraphy or to the evaluation of the cardiac adrenergic system by means of a myocardial MIBG scintigraphy (a norepinephrine storage analogue) can also be helpful to refine the diagnosis. Our experience shows that a good collaboration between the neurologist specialized in movement disorders and the nuclear medicine physician is useful, if not mandatory, to optimize the diagnostic performances of DaTSCAN scintigraphy.

Topics: Brain; Diagnosis, Differential; Essential Tremor; Humans; Movement Disorders; Parkinson Disease; Radionuclide Imaging; Tropanes

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).

Topics: Alzheimer Disease; Brain; Cocaine; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Humans; Iodine Radioisotopes; Lewy Body Disease; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Organotechnetium Compounds; Parkinson Disease; Practice Patterns, Physicians'; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropanes

During the past decade, in vivo imaging of the nigrostriatal dopaminergic system has been developed as a research tool to monitor progressive dopaminergic neuron loss in Parkinson's disease (PD) and to assess the effect of medication on imaging outcomes. Recently two similar studies compared the effect of initial treatment with a dopamine agonist (pramipexole (CALM-PD CIT) or ropinirole (REAL-PET)) or levodopa on the progression of PD as measured by [123I]beta-CIT or [18F]Dopa imaging. These two clinical imaging studies targeting dopamine function with different imaging ligands and technology both demonstrate slowing in the rate of loss of [123I]beta-CIT or [18F]Dopa uptake in early PD patients treated with dopamine agonists compared with levodopa. The relative reduction in the per cent loss from baseline of [123I]beta-CIT uptake in the pramipexole versus the levodopa group was 47% at 22 months, 44% at 34 months and 37% at 46 months after initiating treatment. The relative reduction of 18F-dopa uptake in the ropinirole group versus the levodopa group was 35% at 24 months. These results should be very cautiously interpreted with regard to the effect of dopamine agonists or levodopa on clinical disease progression. These data highlight the need to compare imaging outcomes of dopamine neuronal loss with multiple meaningful clinical endpoints of disease progression in placebo controlled, larger and long-term studies.

Topics: Animals; Antiparkinson Agents; Benzothiazoles; Carrier Proteins; Dihydroxyphenylalanine; Disease Progression; Dopamine Agonists; Dopamine Plasma Membrane Transport Proteins; Humans; Indoles; Iodine Radioisotopes; Levodopa; Membrane Glycoproteins; Membrane Transport Proteins; Neostriatum; Nerve Tissue Proteins; Parkinson Disease; Pramipexole; Radiopharmaceuticals; Thiazoles; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tropanes

To evaluate whether patients with scans without evidence of dopaminergic deficit (SWEDD) have early Parkinson's disease (PD).. The clinical characteristics, striatal specific binding ratios (SBRs), and the indices of I-123 FP-CIT SPECT images of 50 SWEDD patients, 304 PD patients, and 141 healthy controls were acquired from the Parkinson's Progression Markers Initiative (PPMI) data and evaluated during a 2-year clinical follow-up period.. Of the 50 subjects with SWEDD, PD was confirmed in 13 subjects (the PD-SWEDD group), while the remaining 37 subjects had other diseases (the Other-SWEDD group). Striatal SBR values and striatal asymmetry indices of the PD group were significantly different with those of the PD-SWEDD and Other-SWEDD groups at both baseline and after 2 years (p < 0.001). Putaminal SBR values of the PD-SWEDD group were significantly decreased after 2 years (p < 0.05). There was no difference of the SBR values between baseline and after 2 years in the Other-SWEDD group. A baseline MDS-UPDRS III score matched comparison of the PD and PD-SWEDD group was done due to the large difference of the subject numbers. Striatal SBR values and striatal asymmetry indices were significantly different (p < 0.001) between the two groups at both baseline and after 2 years, but there were no significant difference with respect to the MDS-UPDRS III scores after 2 years between the two groups.. The different SBR values and asymmetry indices between the PD and PD-SWEDD groups at baseline and after 2 years indicate that SWEDD may not be early PD, but rather a different disease entity.

Topics: Aged; Corpus Striatum; Dopamine; Humans; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

To determine whether Parkinson disease (PD) affects cross-modal function of vision and olfaction because it is known that PD impairs various cognitive functions, including olfaction.. We conducted behavioral experiments to identify the influence of PD on cross-modal function by contrasting patient performance with age-matched normal controls (NCs). We showed visual effects on the strength and preference of odor by manipulating semantic connections between picture/odorant pairs. In addition, we used brain imaging to identify the role of striatal presynaptic dopamine transporter (DaT) deficits.. We found that odor evaluation in participants with PD was unaffected by visual information, while NCs overestimated smell when sniffing odorless liquid while viewing pleasant/unpleasant visual cues. Furthermore, DaT deficit in striatum, for the posterior putamen in particular, correlated to few visual effects in participants with PD.. These findings suggest that PD impairs cross-modal function of vision/olfaction as a result of posterior putamen deficit. This cross-modal dysfunction may serve as the basis of a novel precursor assessment of PD.

Topics: Aged; Brain; Brain Mapping; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Neuroimaging; Nortropanes; Olfaction Disorders; Olfactory Perception; Parkinson Disease; Radiopharmaceuticals; Semantics; Vision Disorders; Visual Perception

Blepharospasm is a focal dystonia characterized by involuntary cocontraction of the eyelid protractors, causing spasmodic closure of the eyelids. Apraxia of eyelid opening is caused by an inability to initiate lid opening without paralytic abnormality. Some studies suggest that patients with either pure blepharospasm or blepharospasm associated with apraxia of eyelid opening are more prone to developing Parkinson's disease.. In our study,. DAT-SPECT was abnormal in 11 (46%) cases (five patients with isolated blepharospasm and six patients with blepharospasm associated with apraxia of eyelid opening) whose mean disease duration was 11 years.. Our study revealed presynaptic dopaminergic dysfunction, as determined by

Topics: Aged; Apraxias; Blepharospasm; Early Diagnosis; Eyelids; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Predictive Value of Tests; Prodromal Symptoms; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) is a degenerative disorder that affects the central nervous system. PD-related alterations in structural and functional neuroimaging have not been fully explored. This study explored multi-modal PD neuroimaging and its application for predicting clinical scores on the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Multi-modal imaging that combined

Topics: Aged; Connectome; Databases, Factual; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Single Photon Emission Computed Tomography Computed Tomography

Numerous animal studies and clinical trials have demonstrated that erythropoietin (EPO) has therapeutic effects in ischemic and degenerative diseases. However, few clinical trials have investigated the effect of EPO in Parkinson's disease (PD) patients. This study was an exploratory pilot study to investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor symptoms (NMS) in PD patients.. A total of 26 PD patients at the Hanyang University Hospital were enrolled in the study. The participants were randomly assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), the NMS Scale (NMSS) and the 39-Item Parkinson's Disease Questionnaire (PDQ-39). [(18)F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) photon emission tomography (PET) scanning was performed on each participant at baseline and again after 12 months.. The rhEPO administration significantly improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects motor function, did not change significantly after the rhEPO treatment. With the NMSS, the domains of cardiovascular autonomic function, sleep/fatigue, mood/cognition and attention/memory showed significant changes. None of the participants experienced any serious adverse effects.. We found that rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic refractory NMS, such as cardiovascular autonomic dysfunction and cognition, showed improvement after the administration of rhEPO. Our results suggest that rhEPO might be a good candidate for the treatment of NMS in PD patients.

Topics: Aged; Aged, 80 and over; Brain; Cognition Disorders; Erythropoietin; Female; Humans; Male; Mental Disorders; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Single-Blind Method; Sleep Wake Disorders; Surveys and Questionnaires; Time Factors; Tomography, X-Ray Computed; Tropanes; Vascular Diseases

The need for age-adjusted and/or sex-adjusted reference values in dopamine transporter (DAT) and dopamine D2 receptor (D2R) imaging with single-photon emission computed tomography (SPECT) in a longitudinal study of parkinsonian diseases was investigated. We used two different image evaluation tools with a cross-sectional and longitudinal statistical approach.. Baseline DAT and/or D2R SPECT were performed in 51 healthy controls (HC), age-matched to patients in an ongoing prospective study on idiopathic parkinsonism. Twenty-four HC were re-examined after 3 years and 21 HC were examined again after 5 years. SPECT was performed with I-FP-Cit and I-IBZM on a two-headed hybrid gamma camera. Regions of interest and volumes of interest (VOIs) were used for image evaluation. A cross-sectional and longitudinal statistical analysis was carried out.. Fewer sex-based differences and less age dependency were seen in DAT SPECT uptake ratios compared with D2R SPECT uptake ratios and when comparing uptake ratios obtained with regions of interest against those with VOIs. In the cross-sectional analysis, a significant age-dependent decline was seen in women in both DAT and D2R uptakes with the VOI method but not in men with either evaluation method. In the longitudinal dataset, both a slight decline and increase over time were seen in DAT uptake; however, a general pattern of decrease was seen in both men and women in D2R uptake.. The choice of the image evaluation method can influence the pattern of sex-based and age-related differences. The results speak for the use of age-stratified reference values for women, in particular when using a VOI method.

Topics: Adult; Aged; Benzamides; Biological Transport; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Male; Middle Aged; Observer Variation; Parkinson Disease; Prospective Studies; Pyrrolidines; Reference Values; Synapses; Tomography, Emission-Computed, Single-Photon; Tropanes

In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm.. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values.. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%.. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG scintigraphy is likely to significantly increase TA in differentiating PD from APD. The differential diagnosis of degenerative parkinsonism may thus be facilitated.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Algorithms; Benzamides; Diagnosis, Differential; Humans; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Pyrrolidines; Radionuclide Imaging; ROC Curve; Sensitivity and Specificity; Tropanes

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

Topics: Adult; Aged; Aged, 80 and over; Europe; Female; Humans; Iodine Radioisotopes; Longitudinal Studies; Male; Middle Aged; Motor Activity; Parkinson Disease; Reference Values; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

Nicotine therapy might improve the course of Parkinson's disease. This observational study evaluated the performance of dopamine transporter imaging in follow-up patients under nicotine therapy.. Six Hoehn and Yahr stage III patients underwent 123I-FP-CIT imaging prior to, 3 months, and 1 year after the onset of nicotine therapy. Nicotine was administered transdermally with increasing daily doses during 3 months (up to 105 mg/day) and decreased progressively. On co-registered magnetic resonance imaging, striatal regions of interest were drawn and binding potentials of 123I-FP-CIT were calculated.Changes in Unified Parkinson's Disease Rating Scale-III over time were compared with binding potentials using regression analysis.. All patients improved motor scores at 3 months (-65 +/- 22% 'off', -89 +/- 12% 'on') and most received fewer dopaminergic drugs (-30% dosage in average). Motor improvement persisted to a lesser extent at 1 year(-39 +/- 31% 'off', -13 +/- 43% 'on'), partly because one patient stopped the treatment. Interestingly, the decrease in binding potentials (-4.0 +/- 10.5%) was slower than that expected in Parkinsonian patients (usually -10% per year) and was inversely correlated with Unified Parkinson's Disease Rating Scale-III improvement, r= 0.83 'off' and 0.91 'on'.. This observational study emphasizes a potential effect of nicotine therapy on striatal dopamine transporter density, which may be interpreted as direct pharmacological effect or deceleration of neuronal loss.

Topics: Administration, Cutaneous; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neostriatum; Nicotine; Parkinson Disease; Regression Analysis; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

The mechanisms by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) leads to clinical benefit in Parkinson's disease (PD), especially with regard to dopaminergic transmission, remain unclear. Therefore, the objective of our study was to evaluate alterations of synaptic dopaminergic signaling following bilateral STN-DBS in advanced PD within a one-year follow-up. We used [(123)I]FP-CIT single-photon emission computed tomography (SPECT) to measure dopamine transporter (DAT) availability and [(123)I]IBZM SPECT to assess dopamine D(2) receptor (D2R) availability (stimulator ON condition).Patients (n=18) showed a tendency towards a better suppression of symptoms after STN-DBS (Unified Parkinson's Disease Rating Scale motor score with medication decreased from 24.1+/-16.1 to 15.4+/-7.45; p=0. 002) while medication was strongly reduced (61% reduction of levodopa equivalent units; p<0. 0001). No changes of striatal [(123)I]FP-CIT binding and an increase of [(123)I]IBZM binding up to 16% (p<0. 05) between pre-surgery and follow-up investigations were noticed. These data show that clinical improvement and reduction of dopaminergic drugs in patients with advanced PD undergoing bilateral STN-DBS are paralleled by stable DAT and recovery of striatal D2R availability 12 months after surgery.

Topics: Aged; Benzamides; Brain Mapping; Corpus Striatum; Deep Brain Stimulation; Dopamine; Female; Follow-Up Studies; Functional Laterality; Humans; Iodine Isotopes; Male; Middle Aged; Parkinson Disease; Pyrrolidines; Radionuclide Imaging; Subthalamic Nucleus; Tropanes

Single-photon emission computed tomography (SPECT) with [123I]FP-CIT is a marker for loss of presynaptic dopamine transporters in the striatum in Parkinson's disease (PD). We used [123I]FP-CIT SPECT in order to evaluate binding to the dopamine transporter before and after neurosurgical treatment with bilateral stimulation in the subthalamic nucleus (STN).. Thirty-five patients with levodopa-responsive PD were examined with [123I]FP-CIT SPECT pre-operatively (baseline scan: mean 3 months before surgery), and 3 and 12 months after surgery.. Pre-operatively, all patients already had substantial signs of severe nigrostriatal neuronal loss as determined from the [123I]FP-CIT SPECT scans. One year after surgery the specific [123I]FP-CIT binding to the striatum was significantly reduced by 10.3% compared with the pre-operative baseline scan. The mean time span from the baseline scan before surgery to the follow-up scan 1 year after surgery was 16.2 months. Hence, the rate of reduction equals a mean annual reduction of 7.7%. A comparable control group of patients with PD who did not undergo surgery was also examined longitudinally. In this group the specific binding of [123I]FP-CIT was reduced by 6.7% per year.. The specific binding of [123I]FP-CIT was reduced equally in the STN-stimulated patients and a group of non-operated PD patients with advanced disease. Our study does not support the notion that electrode implantation and STN stimulation exert a neuroprotective effect by themselves.

Topics: Adult; Aged; Corpus Striatum; Deep Brain Stimulation; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Radionuclide Imaging; Radiopharmaceuticals; Treatment Outcome; Tropanes

The purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA).. Simultaneous (99m)Tc-ECD/123I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus.. Striatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p<0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p<0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p<0.05).. Dual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes.

Topics: Cysteine; Diagnosis, Differential; Feasibility Studies; Female; Humans; Image Enhancement; Male; Middle Aged; Multiple System Atrophy; Organotechnetium Compounds; Parkinson Disease; Radionuclide Imaging; Reproducibility of Results; Sensitivity and Specificity; Tropanes

It is still debated whether or not I-FP-CIT single photon emission computerized tomography (SPECT) is able to differentiate between Parkinson's disease and progressive supranuclear palsy (PSP). Our aim was to use SPECT semiquantitative analysis to assess the capacity of I-FP-CIT to characterize Parkinson's disease versus PSP.. Twenty-one Parkinson's disease patients, 15 disease duration- and age-matched PSP patients and 20 age-matched healthy controls were included in this study. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (P/O) were calculated in both the basal ganglia. The asymmetric index (AI) for the whole striatum was also calculated for Parkinson's disease and PSP.. Compared to healthy controls, S/O, C/O and P/O were significantly reduced (P<0.001) both in Parkinson's disease (-46%, -43%, -49%, contralaterally to the most affected side; -41%, -37%, -41%, ipsilaterally) and in PSP (-58%, -57%, -59%, contralaterally; -58%, -57%, -59%, ipsilaterally). S/O, C/O and P/O ratio values were significantly (P<0.001) lower in PSP patients when compared to Parkinson's disease group. The asymmetric index (AI) was significantly higher (P<0.001) in Parkinson's disease than in PSP (AI: 23.6%+/-15.07% vs. 9.66%+/-5.83), but with an overlap between the two groups.. Our results confirm that I-FP-CIT SPECT is clinically useful for detecting nigrostriatal degeneration both in Parkinson's disease and PSP. Moreover, in our series, semiquantitative analysis using I-FP-CIT SPECT allowed Parkinson's disease and PSP to be discriminated because PSP patients presented a more severe and symmetric dopamine transporter loss, and the results for S/O were more accurate.

Topics: Aged; Diagnosis, Differential; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

Functional pre-synaptic dopamine brain imaging is generally abnormal when parkinsonism is degenerative (such as in idiopathic Parkinson's disease) and normal in patients with non-degenerative movement disorder (such as essential tremor). However, some patients diagnosed as early Parkinson's disease have normal presynaptic dopamine imaging. Follow-up of patients with normal imaging should help determine whether such patients truly have degenerative parkinsonism (and therefore represent false negative imaging results), or emerge as cases of non-degenerative parkinsonism (and therefore represent initial clinical over-diagnosis of Parkinson's disease).. One hundred and fifty cases with normal I-FP-CIT SPECT undertaken during routine care over a 3-year period were reviewed 2.4 years (interquartile range, 2.2-3.1 years) after SPECT. Diagnosis after follow-up was non-degenerative parkinsonism or tremor in 146 (97%), who did not progress clinically, and degenerative parkinsonism in four (3%), in whom clinical progression was noted. Anti-Parkinson therapy was used in 36, and withdrawn in 27 with no deterioration in 25. Patients strictly fulfilling Brain Bank criteria (part 1) were more likely to undergo a trial of anti-Parkinson therapy (P < 0.05) but were no more likely to maintain or respond to anti-Parkinson therapy than those not fulfilling criteria.. The clinical profile and therapy response during follow-up of patients with normal presynaptic dopamine imaging supports the diagnosis of a non-degenerative movement disorder in nearly all cases.

Topics: Antiparkinson Agents; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tropanes; United Kingdom

We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.

Topics: Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinson's disease (PD) and PD with dementia (PDD) using serial 123I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders.. We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated.. Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p< or =0.01), anterior putamen (DLB, PDD, p< or =0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD.. In conclusion, this is the first study to show that significant progressive dopaminergic loss occurs in DLB and PDD using serial 123I-FP-CIT SPECT. Dementia severity and motor impairment were correlated with decline, suggesting that dopaminergic loss may play an important role in cognitive as well as motor features.

Topics: Aged; Corpus Striatum; Dementia; Disease Progression; Dopamine; Female; Humans; Lewy Body Disease; Male; Parkinson Disease; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

A lack of standardized evaluation procedures for dopamine transporter (DAT) SPECT investigations impairs both intra- and interindividual comparisons as well as multicenter trials-for example, for assessment of disease progression or the response to various drug treatments. Therefore, the aim of this study was to evaluate a novel automated method, which has been specifically developed for a standardized quantification of N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT studies.. DAT binding ratios of 155 (123)I-FP-CIT SPECT studies in 14 control subjects and 141 patients referred to confirm or exclude a presynaptic dopaminergic deficit were determined manually and by a fully automated technique. The latter included coregistration of patient studies to an 123I-FP-CIT mean template of controls with specialized, nonrigid adjustment for variation in striatal location, followed by calculation of specific striatal DAT binding using a standardized 3-dimensional volume-of-interest (VOI) map. The map is based on a MR scan and covers the striatum (S), caudate (C), putamen (P), and an occipital reference region. The semiquantitative ratios of both methods were compared with the visual findings.. Excellent linear correlations were observed between manually and automatically determined results (S: r = 0.99; C: r = 0.99; P: r = 0.99; P < 0.001, respectively). Automated evaluations delivered highly reproducible and visually exact coregistrations. Individual variations in striatal anatomy (e.g., atrophy) were considered and VOI positions were corrected before quantification. Both the manual and the automated method showed identical accuracy in supporting the visual diagnoses.. In a large patient population, excellent agreement was observed between quantitative DAT results using a time-consuming, observer-dependent, conventional manual method and the objective, automated evaluation specifically developed for a standardized evaluation of 123I-FP-CIT SPECT studies. It is suggested that the novel automated technique may substantially facilitate both intra- and interindividual comparisons as well as multicenter trials.

Topics: Adult; Aged; Algorithms; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Observer Variation; Parkinson Disease; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Software; Subtraction Technique; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to evaluate, by means of (123)I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinson's disease.. Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest-occipital)/occipital.. During levodopa wash-out, despite a worsening in patients' clinical disability (H&Y mean stage 2.53+/-0.58 versus 1.73+/-0.45 on therapy, p<0.001), striatal( 123)I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined.. The results of this study suggest that levodopa does not affect( 123)I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT.

Topics: Aged; Antiparkinson Agents; Artifacts; Brain; Dopamine Plasma Membrane Transport Proteins; Drug Interactions; Female; Humans; Image Enhancement; Levodopa; Male; Metabolic Clearance Rate; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, 123I-FP-beta-CIT (FP) and 99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0+/-1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1-2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinson's disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (-8.8%/year, rho=-0.41, P=0.025) and the putamen/caudate ratio (-7.4%/year, rho=-0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.

Topics: Aged; Brain; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Kinetics; Ligands; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tropanes

The occurrence of parkinsonism in Alzheimer's disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson's disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p < 0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.

Topics: Aged; Alzheimer Disease; Basal Ganglia Diseases; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Neostriatum; Nerve Tissue Proteins; Parkinson Disease; Radiopharmaceuticals; Receptors, Presynaptic; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.

Topics: Adult; Aged; Echoencephalography; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Olfaction Disorders; Parkinson Disease; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

The objective of this study was to evaluate the reproducibility of 123I-FPCIT SPECT by using whole striatal region of interest (ROI) and subdivided ROI in normal controls (NC) and Parkinson's disease (PD) patients.. Ten NC and 6 PD received a SPECT scan for 6 hours postinjection of FPCIT. The distribution volume ratio (R(V)) and specific-nonspecific tissue activity ratio (RT) were measured as an outcome measure. The test/retest reproducibility of R(V) and R(T) was evaluated by calculating the test/retest difference, variability, and reliability.. There were no significant test/retest differences for any regions in either the NC or PD. The test/retest variability/reliability of Rv was 5.53+/-4.12%/0.89 in NC, 4.50+/-5.31%/0.99 in PD with whole striatal ROI, 4.29+/-0.78%/ 0.94+/-0.03 in NC, and 6.87+/-1.23 %/0.98+/-0.01 in PD with subdivided ROI. The test/retest variability/reliability of RT was 11.1+/-10.4%/0.59 in NC, 7.84+/-8.94%/0.95 in PD with whole striatal ROI, 11.9+/-1.22%/0.65+/-0.06 in NC, and 12.2+/-4.00%/0.95+/-0.03 in PD with subdivided ROI.. R(V) is highly reproducible and reliable compared with RT in both NC and PD as an outcome measure.

Topics: Adult; Aged; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Radiopharmaceuticals; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tropanes

[123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several "presynaptic parkinsonian" syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [123I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with "presynaptic parkinsonism" from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [123I]FP-CIT SPET. Using [123I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [123I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases, and in three cases no conclusive diagnosis was established, but presynaptic parkinsonism was excluded clinically. A clinical diagnosis of presynaptic parkinsonism was established in two cases: one case of multiple system atrophy (in this patient loss of dopamine D2 receptors was found with [123I]iodobenzamide SPET performed 2 weeks after [123I]FP-CIT imaging) and one case of Parkinson's disease. Our data suggest that the positive predictive value of [123I]FP-CIT imaging is very high, and although the

Topics: Adolescent; Adult; Aged; Carrier Proteins; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Neostriatum; Nerve Degeneration; Nerve Tissue Proteins; Parkinson Disease; Radiopharmaceuticals; Receptors, Presynaptic; Tomography, Emission-Computed, Single-Photon; Tropanes

The main neuropathological feature in Parkinson's disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinson's disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinson's disease, using a one day protocol.. [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinson's disease, and in six age matched healthy volunteers.. Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinson's disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinson's disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinson's disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls.. [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.

Topics: Adult; Aged; Aged, 80 and over; Carrier Proteins; Caudate Nucleus; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Neostriatum; Nerve Tissue Proteins; Parkinson Disease; Pilot Projects; Putamen; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD.. Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [. The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase. The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

Topics: 3-Iodobenzylguanidine; Dopamine Plasma Membrane Transport Proteins; Glucosylceramidase; Humans; Hypotension, Orthostatic; Mutation; Parkinson Disease; Positron-Emission Tomography; Radionuclide Imaging; REM Sleep Behavior Disorder; Tomography, Emission-Computed, Single-Photon; Tropanes

Differential diagnosis between Parkinson's disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), collectively termed atypical Parkinsonism (AP), is challenging. Dopamine transporter density imaging with Ioflupane I. Patients examined at Eginition Hospital (2011-2021), with available DaTscan data and a diagnosis of probable AP, clinically established PD, as well as a neurological control (NC) group were included. Mean binding specific index (BSI), BSI of the most affected side, asymmetry index, laterality, and caudate/putamen ratio were recorded. Analyses were performed by Kruskal-Wallis and ANCOVA.. 137 patients were included (CBD: [Formula: see text]; MSA-P: [Formula: see text]; PSP: [Formula: see text]; PD: [Formula: see text]; NC: [Formula: see text]). There were significant differences when comparing CBS, PSP, and NC vs. all other groups combined. Pairwise between-group comparisons revealed significant differences between PSP and CBD (mean striatum BSI>1.95; sensitivity 74.1%; specificity 85.0%), CBD and MSA-P (mean striatum BSI>2.04; sensitivity 70.4%; specificity 86.7%), and CBD and PD (mean striatum BSI>2.11; sensitivity 66.7%; specificity 100.0%). There were no differences between PSP, MSA-P, and PD. PSP, MSA-P, and PD differed from NC subjects, with 100% specificity and high sensitivity. Differentiation of NC from CBD was suboptimal.. CBD patients exhibit relatively mild DaTscan abnormalities. DaTscan may assist in the differentiation of CBD from PSP. DaTscan does not differentiate among PD, MSA-P, and PSP.

Topics: Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon

Parkinsonism is a term used for the collection of clinical features that cause movement disorders similar to those in Parkinson's disease. Accurate differentiation of these disorders is critical for the treatment and prognosis of any disease. Fluorine-18 N-(3-fluoropropyl)-2β- carboxymethoxy-3β-(4-iodophenyl) nortropane (F-18 FP-CIT) has been used in the evaluation of parkinsonism by its uptake in the dopamine active transporter (DAT) of the striatum. Its uptake in other areas of the brain, such as serotonin transporter (SERT) in the midbrain or thalamus, is also recognised.. To investigate whether midbrain SERT uptake of F-18 FP-CIT on positron emission tomography (PET) could be applied to the differentiation of parkinsonism in combination with striatal DAT uptake.. This retrospective study included clinically diagnosed three essential tremors (ET), 53 parkinsonism patients (21 idiopathic Parkinson's disease (IPD), 6 multiple system atrophy - cerebellar type (MSA-C), 7 multiple system atrophy - parkinsonian type (MSA-P), 8 vascular parkinsonism (VP), and 11 drug-induced parkinsonism (DIP)), and 16 healthy controls. The patient group consisted of 29 men and 27 women (age mean ± SD years, 69.9 ± 8.5 and 69.2 ± 8.9, respectively), and the healthy controls consisted of 8 men and 8 women (age mean ± SD years, 64.5 ± 8.2 and 64.3 ± 7.6, respectively). Mean standardized uptake values (SUVs) and activity volumes were measured from the visualized FP-CIT uptake of the midbrain (substantia nigra and dorsal raphe nucleus) as well as the striatum (caudate nucleus and putamen). The mean SUVs of the occipital region were measured as the background activity. The semiquantitative binding ratio (BR) was calculated using the following formula: BR = (SUVmean of the region of interest - SUVmean of background)/SUVmean of the background. SUV, volume, and BR in each type of parkinsonism were compared with those in healthy controls using both nonparametric and parametric methods. The correlation between the visual score of the qualitative analysis and the BR was examined.. Except for the dorsal raphe nucleus in VP, the midbrain BRs in all parkinsonism showed a statistically significant decrease compared to those in healthy controls. Both midbrain and striatal BRs were significantly decreased only in patients with IPD or MSA-P; a greater decrease of substantia nigra BR was identified in MSA-P than in IPD (p < 0.05). The striatal BRs in MSA-C, VP, and DIP showed no significant difference from those in healthy controls. Finally, four patterns of uptake were identified: 1) decreased striatal and midbrain uptake for IPD and MSA-P, 2) normal striatal uptake and decreased midbrain uptake (both substantia nigra and dorsal raphe nucleus) for MSA-C and DIP, 3) normal striatal uptake and decreased substantia nigra uptake (without decreased dorsal raphe nucleus uptake) for VP, and 4) normal striatal and midbrain uptake for ET.. The possible differential diagnoses were split into two groups when only striatal uptake was considered but they were divided into four groups after adding midbrain uptake. Although additional midbrain F-18 FP-CIT uptake still could not make a final definitive diagnosis, it could provide another piece of information and specific diagnostic guidelines for the differentiation of parkinsonism.

Topics: Essential Tremor; Female; Humans; Male; Mesencephalon; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

Dysregulation of the CD4 + T cell compartment occurs in Parkinson's Disease (PD). Nonetheless, the exact relationship with dopamine transporter (DAT) SPECT denervation patterns is currently unknown.. FOXP3 mRNA levels correlated with the uptake in maC (r = - 0.542, P = 0.011), laP (r = - 0.467, P = 0.033), and tSBR (r = - 0.483, P = 0.027). Concerning flow cytometry analysis of circulating CD4 + T cell subsets, a significant relationship between tP/C, caudate uptake, and the levels of both T helper (Th)1 and 2, was detected. Furthermore, we found significant correlations between the uptake in maP and the total count of naïve and activated T regulatory cells (Treg) (r = - 0.717, P = 0.001; r = - 0.691, P = 0.002), which were confirmed after the Benjamini-Hochberg correction for multiple comparisons using a false discovery rate at level q = 0.10. Levels of circulating naïve Treg were higher (P = 0.014) in patients with more extensive dopaminergic denervation, suggesting a compensatory phenomenon.. Peripheral CD4 + T cell immunity is involved in early-stage PD and novel correlations with striatal DAT loss were observed.

Topics: CD4-Positive T-Lymphocytes; Dopamine Plasma Membrane Transport Proteins; Humans; Leukocytes, Mononuclear; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

[ 18 F]FE-PE2I (FE-PE2I) is a new radiotracer for dopamine transporter (DAT) imaging with PET. The aim of this study was to evaluate the visual interpretation of FE-PE2I images for the diagnosis of idiopathic Parkinsonian syndrome (IPS). The inter-rater variability, sensitivity, specificity, and diagnostic accuracy for visual interpretation of striatal FE-PE2I compared to [ 123 I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) was evaluated.. Thirty patients with newly onset parkinsonism and 32 healthy controls with both an FE-PE2I and FP-CIT were included in the study. Four patients had normal DAT imaging, of which three did not fulfil the IPS criteria at the clinical reassessment after 2 years. Six raters evaluated the DAT images blinded to the clinical diagnosis, interpreting the image as being 'normal' or 'pathological', and assessed the degree of DAT-reduction in the caudate and putamen. The inter-rater agreement was assessed with intra-class correlation and Cronbach's α . For calculation of sensitivity and specificity, DAT images were defined as correctly classified if categorized as normal or pathological by ≥4/6 raters.. The overall agreement in visual evaluation of the FE-PE2I- and FP-CIT images was high for the IPS patients ( α  = 0.960 and 0.898, respectively), but lower in healthy controls (FE-PE2I: α  = 0.693, FP-CIT: α  = 0.657). Visual interpretation gave high sensitivity (both 0.96) but lower specificity (FE-PE2I: 0.86, FP-CIT: 0.63) with an accuracy of 90% for FE-PE2I and 77% for FP-CIT.. Visual evaluation of FE-PE2I PET imaging demonstrates high reliability and diagnostic accuracy for IPS.

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Parkinson Disease; Positron Emission Tomography Computed Tomography; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [. To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.. We assessed clinical features, the peripheral immune profile, and striatal [. A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β = -0.01, p < 0.001; PPMI-cohort: β = -0.05, p = 0.05) and the putamen (primary-cohort: β = -0.05, p = 0.02; PPMI-cohort: β = -0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β = +0.09, p < 0.05; PPMI-cohort: β = +0.11, p = 0.02) and the putamen (primary-cohort: β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β = -0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = -0.04, p = 0.08; PPMI-cohort: β = -0.01, p = 0.73).. Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Topics: Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Humans; Inflammation; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Nigrosome 1 (NG1), a small cluster of dopaminergic cells in the substantia nigra and visible in the susceptibility map-weighted magnetic resonance image (SMwI), is severely affected in Parkinson's disease (PD). However, the degree of nigrostriatal degeneration according to the visibility of NG1 has not yet been well elucidated.. We consecutively recruited 138 PD and 78 non-neurodegenerative disease (non-ND) patients, who underwent both. Visual rating of NG1 showed excellent interobserver agreements as well as high sensitivity and specificity to differentiate the PD group from the non-ND group. NG1 was visible in seven patients (5.1%) in the PD group, who had relatively short disease duration or less severe loss of striatal dopamine. The threshold of putaminal SBR reduction on the more affected side for the disappearance of NG1 was 45.5%, and the probability for NG1 visibility dropped to 50% after the reduction of putaminal SBR to 41% from the normal mean.. Almost half loss of nigrostriatal dopaminergic input is required to dissipate the hyperintensity of NG1 on SMwI, suggesting its utility in diagnosing PD only after the onset of the motor symptoms.

Topics: Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Humans; Parkinson Disease; Positron-Emission Tomography; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Nigrosome imaging using susceptibility-weighted imaging (SWI) and dopamine transporter imaging using. Between February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and. We included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39-88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted. A deep learning-based regressor model effectively predicted striatal

Topics: Aged; Biomarkers; Deep Learning; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon; Tropanes

Gastrointestinal symptoms are common in Parkinson's disease (PD), but their neurophysiological correlates are not well understood. We recently reported that functional gastrointestinal symptoms were not associated with asymmetry per se but might be associated with lower left striatal dopamine transporter (DAT) binding. The purpose of this study was to further investigate if specific gastrointestinal symptoms associate with monoamine transporter changes in specific striatal or extrastriatal areas.. Ninety PD patients, who underwent DAT ¹. Irritable bowel syndrome (IBS) criteria were fulfilled in 17 patients and were linked to higher ¹. These findings suggest that PD patients with IBS may have higher DAT binding in the right hemisphere. This finding implicates alterations of brain neurotransmitter physiology in the gastrointestinal symptoms of PD patients.

Topics: Brain; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Humans; Irritable Bowel Syndrome; Parkinson Disease; Serotonin Plasma Membrane Transport Proteins

Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with. Twenty iRBD patients underwent two consecutive. Individual hypometabolism t-maps revealed three scenarios: (1) normal. Our results suggest that occipital hypometabolism at baseline in iRBD implies a short-term conversion to PD. This might help in stratification strategies for disease-modifying trials.

Topics: 3-Iodobenzylguanidine; Fluorodeoxyglucose F18; Humans; Parkinson Disease; Positron-Emission Tomography; REM Sleep Behavior Disorder; Risk Factors

18 F-FP-CIT PET/CT is a useful diagnostic tool for differentiating between idiopathic Parkinson disease and atypical Parkinson syndrome by visualizing the striatum, where the nerve endings of nigrostriatal dopaminergic neurons are located. We present an unusual accumulation of 18 F-FP-CIT in the infarct and peri-infarct brain area of an 83-year-old man who was referred for the management of suspected cerebral infarction due to sudden dysarthria and delirium.

Topics: Aged, 80 and over; Cerebral Infarction; Dopamine Plasma Membrane Transport Proteins; Humans; Male; Parkinson Disease; Positron Emission Tomography Computed Tomography; Tomography, Emission-Computed, Single-Photon; Tropanes

A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed. The SUVR in early. Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early

Topics: Biomarkers; Dopamine Plasma Membrane Transport Proteins; Humans; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon

To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD).. We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase. There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD-CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD-iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD-CIS group did not differ from that in the PD-iCIS and PD-nCIS groups. Meanwhile, the PD-iCIS group had a higher risk of dementia conversion than the PD-nCIS group.. The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.

Topics: Dementia; Humans; Parkinson Disease; Positron-Emission Tomography; Tropanes

Glymphatic dysfunction can contribute to α-synucleinopathies. We examined glymphatic function in idiopathic Parkinson's disease (PD) utilizing Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS).. This study enrolled consecutive patients diagnosed with de novo PD between June 2017 and March 2019 who underwent brain DTI with concurrent. In all, 54 patients in the de novo PD group (31 women, 23 men; mean age, 68.9 ± 9.4 years) and 54 in the control group (mean age, 69.0 ± 10.5 years) were included. The ALPS-index was lower in the PD group than in the controls (1.51 ± 0.22 versus 1.66 ± 0.20; P < 0.001). In the PD group, the ALPS-index negatively correlated with the UPDRS-III score (r = -0.526), and positively correlated with the MMSE (r = 0.377) and MoCA scores (r = 0.382) (all, P < 0.05). No correlation was observed between the ALPS-index and striatal. DTI-ALPS can reveal glymphatic dysfunction in patients with PD, whose severity correlated with motor and cognitive dysfunction, but not striatal dopamine transporter uptake.

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Tropanes

Topics: 3-Iodobenzylguanidine; Aged; alpha-Synuclein; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Heart; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radionuclide Imaging; Radiopharmaceuticals; Tropanes

The specific binding ratio (SBR) is an objective indicator of N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[123I] iodophenyl) nortropane ([

Topics: Atrophy; Biomarkers; Brain; Computer Simulation; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Humans; Image Interpretation, Computer-Assisted; Lewy Body Disease; Monte Carlo Method; Neurodegenerative Diseases; Parkinson Disease; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

Spatial normalization helps us to compare quantitatively two or more input brain scans. Although using an affine normalization approach preserves the anatomical structures, the neuroimaging field is more common to find works that make use of nonlinear transformations. The main reason is that they facilitate a voxel-wise comparison, not only when studying functional images but also when comparing MRI scans given that they fit better to a reference template. However, the amount of bias introduced by the nonlinear transformations can potentially alter the final outcome of a diagnosis especially when studying functional scans for neurological disorders like Parkinson's Disease. In this context, we have tried to quantify the bias introduced by the affine and the nonlinear spatial registration of FP-CIT SPECT volumes of healthy control subjects and patients with PD. For that purpose, we calculated the deformation fields of each participant and applied these deformation fields to a 3D-grid. As the space between the edges of small cubes comprising the grid change, we can quantify which parts from the brain have been enlarged, compressed or just remain the same. When the nonlinear approach is applied, scans from PD patients show a region near their striatum very similar in shape to that of healthy subjects. This artificially increases the interclass separation between patients with PD and healthy subjects as the local intensity is decreased in the latter region, and leads machine learning systems to biased results due to the artificial information introduced by these deformations.

Topics: Humans; Magnetic Resonance Imaging; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Micrographia is a common symptom of Parkinson's disease (PD), and it may precede other motor symptoms. Despite the high prevalence of micrographia in PD, its neurobiological mechanisms are not known. Given that levodopa may alleviate consistent micrographia and that nondopaminergic essential tremor (ET) is not associated with micrographia, micrographia could possibly be used as an ancillary diagnostic method that reflects nigrostriatal dopamine function. We evaluated the usefulness of micrographia as a simple one-sentence writing test in differentiating PD from ET. A total of 146 PD patients, 42 ET patients and 38 healthy controls provided writing samples and were scanned with brain [

Topics: Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Humans; Iodine Radioisotopes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The AUC was high with all ML methods (0.92-0.96) for high or low uptake. The AUC was the highest for symmetry or asymmetry with the kNN method (AUC 0.75) and the comma-dot feature with the GBT method (AUC 0.94). Based on the test data set, the diagnostic accuracy for a diagnosis of PS/PD/DLB was 0.86 ± 0.04 (SE), 0.87 ± 0.04, and 0.93 ± 0.02 for Models 1, 2 and 3, respectively. The AUC was optimal for Model 3, and significantly differed between Models 3 and 1 (p = 0.027), and 3 and 2 (p = 0.029).. Image features such as high or low uptake, symmetry or asymmetry, and comma- or dot-like profiles can be determined using ML. The diagnostic accuracy of differentiating PS/PD/DLB was the highest for the multivariate model with three features and age compared with the conventional ROI-based method.

Topics: Alzheimer Disease; Diagnosis, Differential; Humans; Iodine Radioisotopes; Lewy Body Disease; Machine Learning; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter SPECT with

Topics: Brain; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Humans; Image Interpretation, Computer-Assisted; Nerve Degeneration; Neural Networks, Computer; Parkinson Disease; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Striatal dopamine transporter (DAT) uptake assessment through I

Topics: Aged; Catechol O-Methyltransferase; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Genotype; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon

To determine whether vascular parkinsonism (VaP) patients with visually normal dopamine transporter (DAT) scans have presynaptic dopaminergic depletion.. We enrolled 23 VaP patients who had parkinsonism, relevant diffuse subcortical white matter hyperintensities (WMH), and visually normal DAT scans, 23 Parkinson's disease (PD) patients, and 31 control subjects. By quantitatively analyzing. VaP patients exhibited decreased DAT availability in all striatal subregions, including posterior putamen, compared to control subjects. VaP patients and control subjects had similar patterns of anteroposterior and ventrodorsal DAT gradients in caudate and putamen level, but VaP patients exhibited significantly different patterns at putamen level, relative to PD patients. The severity of periventricular WMH was significantly correlated with all substriatal DAT availability in VaP, but not with UPDRS-III scores. The ROC analysis showed that DAT availability in caudate and posterior putamen had a fair discriminatory power when differentiating VaP patients from control subjects.. This study demonstrates that VaP patients with WMH exhibited diffusely decreased DAT availability without any specific regional gradients of DAT patterns distinct from either control subjects or PD patients.

Topics: Aged; Aged, 80 and over; Cerebrovascular Disorders; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Leukoaraiosis; Male; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Retrospective Studies; Tropanes

Reproducibility was excellent, with low variability (ET: 6.99-8.02%, PD: 3.51-6.94%) and high reliability (ICC; ET: 0.88-0.96, PD: 0.98-0.99). The ET group showed higher variability and lower ICCs than the PD group. The variability in the 90-min images (ET: 7.85-8.59%, PD: 1.52-2.75%) was comparable to that in the 3-h images (ET: 6.99-8.02%, PD: 3.51-6.94%). There were no differences in variability among the subregions in the ET group. In the PD group, the variability was high in the posterior putamen (automatic method: 6.94%, manual method: 11.80%). The test-retest variability and ICCs were similar for the manual and automatic methods.. [

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron Emission Tomography Computed Tomography; Reproducibility of Results; Tropanes

Our aim was to develop and validate a machine learning (ML)-based approach for interpretation of I-123 FP-CIT SPECT scans to discriminate Parkinson's disease (PD) from non-PD and to determine its generalizability and clinical value in two centers.. We retrospectively included 210 consecutive patients who underwent I-123 FP-CIT SPECT imaging and had a clinically confirmed diagnosis. Linear support vector machine (SVM) was used to build a classification model to discriminate PD from non-PD based on I-123-FP-CIT striatal uptake ratios, age and gender of 90 patients. The model was validated on unseen data from the same center where the model was developed (n = 40) and consecutively on data from a different center (n = 80). Prediction performance was assessed and compared to the scan interpretation by expert physicians.. Testing the derived SVM model on the unseen dataset (n = 40) from the same center resulted in an accuracy of 95.0%, sensitivity of 96.0% and specificity of 93.3%. This was identical to the classification accuracy of nuclear medicine physicians. The model was generalizable towards the other center as prediction performance did not differ thereby obtaining an accuracy of 82.5%, sensitivity of 88.5% and specificity of 71.4% (p = NS). This was comparable to that of nuclear medicine physicians (p = NS).. ML-based interpretation of I-123-FP-CIT scans results in accurate discrimination of PD from non-PD similar to visual assessment in both centers. The derived SVM model is therefore generalizable towards centers using comparable acquisition and image processing methods and implementation as diagnostic aid in clinical practice is encouraged.

Topics: Aged; Female; Humans; Image Interpretation, Computer-Assisted; Machine Learning; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopamine transporter single-photon emission computed tomography (DAT SPECT) has been widely used to diagnose Parkinson syndrome. Using the standardized uptake value (SUV) of DAT SPECT, we propose "functional dopamine transporter volume (f-DTV)" as a new quantitative index to evaluate the three-dimensional volume of functional dopamine transporters and assess its diagnostic ability in differentiating dopaminergic neurodegenerative diseases (dNDD) from non-dNDD.. Seventy-nine patients were enrolled (42 dNDD, 37 non-dNDD; 38 men; age 24-88 years). We analyzed seven quantitative indices. The specific binding ratio (SBR) was calculated using a program specialized for DAT SPECT (SBR_Bolt). The SUVmax, SUVpeak, and SUVmean were calculated using a quantification program for bone SPECT. SBR_SUV was calculated by dividing striatal SUVmean by the average of background SUVmean. The cutoff value of the active dopamine transporter level was examined using three methods (threshold of 40% of SUVmax, SUV 2, and SUV 3) to calculate the active dopamine transporter volume (ADV). The f-DTV was calculated by multiplying ADV and SUV. The SBR_Bolt and SBR_SUV highly correlated with each other (r = 0.71). The cutoff value of the active dopamine transporter level was determined as SUV 3. All seven quantitative indices showed lower values in the dNDD group than in the non-dNDD group, and the difference between the two groups was statistically significant (p < 0.05). Sensitivity, specificity, and AUC of f-DTV were slightly lower than those of SBR_Bolt (71%, 79%, and 0.81, respectively, for f-DTV, and 81%, 84%, 0.88, respectively, for SBR_Bolt). The difference in AUC between f-DTV and SBR_Bolt was not statistically significant.. This study demonstrates the utility of f-DTV as a novel quantitative index for evaluating the three-dimensional volume of functional dopamine transporters, and that f-DTV has almost the same diagnostic ability to differentiate dNDD from non-dNDD using DAT SPECT.

Topics: Adult; Aged; Aged, 80 and over; Biological Transport; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Phantoms, Imaging; Retrospective Studies; ROC Curve; Tomography, Emission-Computed, Single-Photon

Despite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).. In this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the "pROC" package of R (version 1.16.2).. The area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912-1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.. Our deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.

Topics: Aged; Deep Learning; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Reproducibility of Results; Retrospective Studies; Substantia Nigra; Tropanes

Parkinson's disease (PD) is the most common degenerative cause of movement disorder, and autonomic dysfunction has been recognized in this disorder. PD patients' lower urinary tract (LUT) function is not established. We investigated LUT function in PD by single-photon emission computerized tomography (SPECT) imaging of the dopamine transporter with. We retrospectively analyzed the cases of 30 patients diagnosed with PD based on published criteria who completed a systematized lower urinary tract symptoms (LUTS) questionnaire and a urodynamics examination irrespective of the presence of LUTS. None of the patients were taking anti-parkinsonian medication during the study.. The questionnaire revealed that all 30 patients had LUTS: night-time urinary frequency (in 70%), urinary incontinence (40%), and daytime urinary frequency (80%). A urodynamic study revealed a mean volume at the first sensation at 92.3 ml, bladder capacity at 200.9 ml, and detrusor overactivity in 50%. Sphincter electromyography revealed neurogenic change in 13.6% of those for whom the test was performed. The average SBR showed a significant correlation with bladder capacity (Spearman's correlation coefficient p = 0.0076) and Hoehn Yahr motor stage (Spearman's correlation coefficient p = 0.012).. Our findings demonstrate that the striatum is relevant to the higher control of storage in micturition function in PD.

Topics: Humans; Nortropanes; Parkinson Disease; Pharmaceutical Preparations; Radionuclide Imaging; Retrospective Studies; Urinary Bladder; Urodynamics

Although functional imaging is useful for the diagnosis and pathophysiological evaluation of Parkinson's disease (PD), little is known about the relationship between functional imaging findings and PD clinical features. The objective of this study was to determine the relationship between. The study included 46 drug-naive patients with early-stage PD. The specific binding ratios (SBRs) in the striatum and its subregions, namely anterior/posterior putamen and caudate nucleus, were calculated in patients who underwent. The mean SBRs of the striatum and anterior putamen were significantly associated with the modified HY stage and UPDRS part III score. The mean SBR of the caudate nucleus was significantly associated with the UPDRS part III score. The mean striatal SBR was also significantly associated with the mean gait cycle duration and mean gait acceleration amplitude.. The mean striatal SBR, as determined by

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Parkinson Disease; Pharmaceutical Preparations; Tomography, Emission-Computed, Single-Photon; Tropanes

Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD).. We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage.. We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined.. In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL.. The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Topics: Alzheimer Disease; Brain; Cognition Disorders; Fluorodeoxyglucose F18; Humans; Movement Disorders; Neurodegenerative Diseases; Nortropanes; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

Delayed phase

Topics: Aged; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Positron-Emission Tomography; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Tropanes

The role of nigrostriatal dopaminergic neurons degeneration is well established in the pathophysiology of Parkinson's disease. However, it is unclear if and how the degeneration of the dopamine pathways affects the manifestation of the neuropsychiatric symptoms (NPS) of Parkinson's Disease (PD). Dopamine transporter (DAT) imaging, a technique to measure the reduction in dopamine transporters is increasingly used as a tool in the diagnosis of PD.. In this study, we examine if the baseline dopamine transporter density in the striatum measured by the Striatal Binding Ratio (SBR) is associated with the longitudinal onset and/or progression of NPS in PD as measured by part 1 of Movement Disorder Society - Unified Parkinson's Disease Rating Scale, over four years. Data of patients with PD and an abnormal screening present on 123I-ioflupane single-proton emission computed tomography were obtained from Parkinson's Progression Markers Initiative (PPMI) database. Latent Growth Modeling (LGM), a statistical technique that can model the change over time while considering the variability in the rate of change at the individual level, was used to examine the progression of NPS over time.. The results indicate the SBR did not correlate with the baseline NPS but did correlate with the rate of change of NPS (p<0.001) over the next four years, even after eliminating age-related variance, which can be a significant confounding factor.. In conclusion, this study showed gradual worsening in NPS in patients with Parkinson's disease, which inversely correlates with the density of the dopamine transporters as measured by SBR at baseline.

Topics: Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

Rapid eye movement sleep behavior disorder (RBD) patients have a high risk of developing a Parkinsonian disorder, offering an opportunity for neuroprotective intervention. Predicting near-term conversion, however, remains a challenge. Dopamine transporter imaging, while informative, is expensive and not widely available. Here, we investigate the utility of susceptibility-weighted MRI (SWI) to detect abnormalities of the substantia nigra in RBD, and explore their association with striatal dopaminergic deficits.. Consensus visual DNH classification was possible in 87% of participants. 27.5% of RBD patients had lost DNH, compared with 7.7% of control subjects and 96% of Parkinson's patients. RBD patients lacking DNH had significantly lower putamen dopaminergic SPECT/CT activity compared to RBD patients with DNH present (specific uptake ratios 1.89 vs. 2.33, P = 0.002). The mean quantified DNH signal intensity declined in a stepwise pattern, with RBD patients having lower intensity than controls (0.837 vs. 0.877, P = 0.01) but higher than PD patients (0.837 vs. 0.765, P < 0.001).. Over one quarter of RBD patients have abnormal substantia nigra SWI reminiscent of Parkinson's, which is associated with a greater dopaminergic deficit. This modality may help enrich neuroprotective trials with early converters.

Topics: Aged; Cohort Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Neuroimaging; Nortropanes; Parkinson Disease; Pars Compacta; Putamen; REM Sleep Behavior Disorder; Single-Blind Method; Tomography, Emission-Computed, Single-Photon

The present study investigated possible associations between cortical dysfunction/degeneration as measured by F-FDG PET and nigrostriatal degeneration according to the specific I-FP-CIT binding ratio (SBR) in striatal subregions defined by striato-cortical anatomical connectivity in Parkinson disease (PD) patients.. The study included 41 patients (61.4 ± 12.8 years) with PD-typical reduction of striatal FP-CIT SBR and no sign of atypical parkinsonian syndrome on FDG PET. FP-CIT SBR was determined separately in the cognitive (composite of executive and limbic) and sensorimotor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Scaled FDG uptake was tested voxelwise for correlation with FP-CIT SBR (familywise error corrected P < 0.05).. A large cluster (17.6 mL) of significant correlation of scaled FDG uptake with FP-CIT SBR in the cognitive part of the striatum, corrected for SBR in the sensorimotor part, was detected in the bilateral medial frontal cortex and the anterior cingulate cortex (partial correlation coefficient R = 0.767); small clusters were detected in ipsilateral caudate and ipsilateral thalamus. There was a small contralateral occipital cluster (3.0 mL) of significant correlation between FDG uptake and sensorimotor SBR corrected for cognitive SBR (R = 0.709).. The correlation between nigrostriatal degeneration in the cognitive striatum and reduced cerebral glucose metabolism in the medial parts of the frontal cortex including the anterior cingulate suggests that nigrostriatal degeneration is specifically involved in the pathogenesis of cognitive deficits associated with medial frontal dysfunction such as impaired inhibitory control.

Topics: Aged; Cognition; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Fatigue is one of the most common non-motor symptoms in Parkinson's disease (PD). Despite its clinical importance, there are few studies on the cause or mechanism of fatigue. Our aim was to find brain areas related to fatigue and to explore the association between striatal dopaminergic dysfunction and fatigue. We consecutively screened forty-seven patients with de novo PD from 2012 to 2017 and enrolled 32 patients. The gray matter volumes, white matter tracts, and striatal dopaminergic activity between PD without fatigue and with fatigue were compared. The correlation between fatigue and striatal dopaminergic activity was also analyzed. Our data did not show any significant difference in gray matter volume between PD without fatigue and with fatigue (familywise error [FWE] corrected p > 0.05) but revealed significantly higher mean fractional anisotropy (FA) values for all analyzed white matter tracts in PD with fatigue (false discovery rate [FDR] corrected p < 0.05), except left cingulum-hippocampus (CH), right superior longitudinal fasciculus, and right longitudinal fasciculus temporal part (FDR corrected p > 0.06); lower mean diffusivity (MD) values for all analyzed white matter tracts in PD with fatigue (FDR corrected p < 0.05), except in the left CH and uncinate fasciculus (FDR corrected p > 0.05). The mean radial diffusivity (RD) values, except for the left CH (FDR corrected p = 0.0576), were also significantly lower (FDR corrected p < 0.05). There was no difference in dopaminergic deficits between PD without fatigue and PD with fatigue (p > 0.50). The alteration of the white matter tract may reflect the degree of fatigue in PD. This is not true of the gray matter and striatal dopaminergic activity. These results show the possibility that white matter changes can be used as a biomarker for fatigue.

Topics: Aged; Aged, 80 and over; Diffusion Tensor Imaging; Dopamine; Fatigue; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Tropanes; Ventral Striatum; White Matter

Neuroinflammation in Parkinson's disease (PD) is known to play a pivotal role in progression to neuronal degeneration. It has been reported that colony-stimulation factor 1 receptor (CSF-1R) inhibition can effectively deplete microglia. However, its therapeutic efficacy in PD is unclear still now.. To elucidate this issue, we examined the contribution of microglial depletion to PD by behavioral testing, positron emission tomography (PET) imaging, and immunoassays in sham, PD, and microglial depletion PD model (PLX3397 was administered to PD groups, with n = 6 in each group).. The microglial depletion in PD model showed improved sensory motor function and depressive-like behavior. NeuroPET revealed that PLX3397 treatment resulted in partial recovery of striatal neuro-inflammatory functions (binding values of [. Microglial depletion has inflammation-related therapeutic effects, which have beneficial effects on motor and nonmotor symptoms of PD.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Dopamine; Glutamic Acid; Male; Microglia; Neuroprotective Agents; Parkinson Disease; Positron-Emission Tomography; Pyrazoles; Pyrimidines; Rats, Sprague-Dawley; Receptor, Macrophage Colony-Stimulating Factor; Swimming; Tropanes

Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS.. Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS.. At baseline, 11, 6, and 2 among 19 patients had left-side-dominant, right-side-dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively.. The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.

Topics: Aged; Deep Brain Stimulation; Female; Functional Laterality; Humans; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

We have evaluated the clinical significance of the washout rate (WR) on I-123 MIBG scans through the analysis of the relationship between the I-123 MIBG scans and autonomic status in patients with Parkinson's disease (PD).. Sixty patients with clinical PD who had decreased HMR were enrolled. An autonomic symptom was evaluated using a head-up tilt test and the Composite Autonomic Severity Score (CASS). An I-123 MIBG scan and F-18 FP-CIT positron emission tomography (PET) were performed. All of the patients were classified into three groups according to the WR. The differences in patient characteristics and the imaging parameters among the three groups were evaluated, and a correlation analysis was also performed.. The frequency of orthostatic hypotension was significantly different among the three groups. The difference in systolic pressure (dSysPr) and the difference in diastolic pressure (dDiaPr) of group 3 was significantly larger than those of groups 1 and 2. From the correlation analysis, it can be seen that age, Hoehn and Yahr (H&Y) stage, dSysPr, and dDiaPr had a weak positive correlation with the WR. The total CASS score was significantly higher in group 3 compared with groups 1 and 2. The WR had a moderate positive correlation with the cardiosympathetic score and the total CASS score.. The WR is related to autonomic dysfunction. An I-123 MIBG cardiac scan is considered to be a good method to evaluate not only the differential diagnosis of Parkinson's disease but also the degree of autonomic dysfunction.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Autonomic Nervous System; Blood Pressure; Female; Fluorine Radioisotopes; Heart; Humans; Hypotension, Orthostatic; Iodine Radioisotopes; Male; Mediastinum; Middle Aged; Parkinson Disease; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Retrospective Studies; Tropanes

Autonomic dysfunction is a common non-motor symptom in Parkinson's disease (PD). Dopamine and serotonin are known to play a role in autonomic regulation, and, therefore, PD-related degeneration of serotonergic and dopaminergic neurons in these regions may be associated with autonomic dysfunction. We sought to clarify the association between extrastriatal serotonergic and striatal dopaminergic degeneration and the severity of autonomic symptoms, including gastrointestinal, pupillomotor, thermoregulatory, cardiovascular, and urinary dysfunction. We performed hierarchical multiple regression analyses to determine the relationships between (extra)striatal serotonergic and dopaminergic degeneration and autonomic dysfunction in 310 patients with PD. We used [

Topics: Aged; Autonomic Nervous System Diseases; Caudate Nucleus; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Our rationale was to conduct a retrospective study comparing 3

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Corpus Striatum; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

To evaluate the real-world diagnostic performance of high-resolution susceptibility-weighted imaging (HR-SWI) and investigate whether the reader's predictions can be used to find cases where HR-SWI finding and final clinical diagnosis matched.. This retrospective study enrolled patients with suspected Parkinsonism (n = 48) or volunteers with other intracranial pathologies (n = 31) who underwent brain magnetic resonance imaging (MRI) including HR-SWI, which was used to evaluate nigrosome 1 (NG1). All patients with suspected Parkinsonism underwent N-3-fluoropropyl-2-carbomethoxy-3-4-iodophenyl nortropane (FP-CIT) positron emission tomography and a clinical diagnosis was made by a neurologist. The HR-SWI data were qualitatively analyzed by two independent reviewers. A consensus reading was performed and a diagnostic confidence score was assigned. According to final clinical diagnosis, diagnostic sensitivity, specificity, and accuracy were calculated. Receiver operating characteristic (ROC) curve analysis was used to examine whether the diagnostic confidence score could be used to identify HR-SWI finding-final clinical diagnosis matched cases.. Of the 48 patients with suspected Parkinsonism, 31 were diagnosed with idiopathic Parkinson's disease, and three with multiple system atrophy. The remaining 14 patients were included in the disease control group. Of the 31 volunteers, 10 subjects were excluded due to possibility of nigrostriatal degeneration and finally 21 subjects were enrolled as controls with non-Parkinsonism pathology (non-PD control). After consensus reading, 25 subjects were classified as true positive and 28 as true negative, according to HR-SWI findings. The calculated diagnostic sensitivity, specificity, and accuracy were 73.5%, 80.0%, and 76.8%, respectively. With using diagnostic concordance score, the area under the ROC curve for the detection of concordance case was 0.83 (95% CI: 0.72-0.91, p < 0.05).. The diagnostic performance of NG1 detection using HR-SWI with 3T MRI was within acceptable range. Using the reader's diagnostic confidence could be helpful to find cases which HR-SWI finding and final clinical conclusion match. So HR-SWI may be of added value in the evaluation of suspected Parkinsonism.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Sensitivity and Specificity; Tropanes

Parkinson's disease (PD) affects the integrity of the dopamine and serotonin system, and is characterized by a plethora of different symptoms, including cognitive impairments of which the pathophysiology is not yet fully elucidated.. Investigate the role of the integrity of the dopaminergic and serotonergic system in cognitive functioning in early-stage PD using Single Photon Emission Computed Tomography (SPECT) combined with the radiotracer. We studied the association between cognitive functions and dopamine transporter (DAT) availability in the caudate nucleus and putamen - as a proxy for striatal dopaminergic integrity - and serotonin transporter (SERT) availability as a proxy for serotonergic integrity in the thalamus and hippocampus using bootstrapped multiple regression. One-hundred-and-twenty-nine (129) PD patients underwent a. We showed a positive association between DAT availability in the head of the caudate nucleus and the Stroop Color Word Task - card I (reading words; β = 0.32, P = 0.001) and a positive association between DAT availability in the anterior putamen and the Trail Making Test part A (connecting consecutively numbered circles; β = 0.25, P = 0.02). These associations remained after adjusting for motor symptom severity or volume of the region-of-interest and were most pronounced in medication-naïve PD patients. There were no associations between cognitive performance and SERT availability in the thalamus or hippocampus.. We interpret these results as a role for striatal dopamine - and its PD-related decline - in aspects of processing speed.

Topics: Aged; Cognition; Cognitive Dysfunction; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of the study is to evaluate the impact of myocardial I-metaiodobenzylguanidine (MIBG) in the diagnosis, clinical management, and differential diagnosis of Parkinson disease (PD) and non-PD parkinsonism.. The study enrolled 41 patients with parkinsonism. An initial diagnosis was reached after thorough clinical and imaging evaluation. After 2 to 5 years of follow-up, a final diagnosis was established. All patients underwent, soon after their initial visit, presynaptic striatal DaT scintigraphy with I-FP-CIT (DaTscan) and I-MIBG myocardial scintigraphy. DaTscan is not specific to distinguish among different types of neurodegenerative parkinsonism. I-MIBG myocardial scintigraphy displays the functional status of cardiac sympathetic nerves, which is reduced in PD/dementia with Lewy bodies (DLB) and normal in atypical parkinsonian syndromes and secondary or nondegenerative parkinsonism.. No patients showed adverse effects during or after both scintigraphies. A positive DaTscan was found in all patients in the PD/DLB group (17/17) and in 15 of 24 patients in the non-PD group. Myocardial I-MIBG scintigraphy was associated with lower sensitivity (82% vs 100%) but higher specificity than DaTscan (79% vs 38%) in diagnosis PD/DLB from non-PD parkinsonism. A positive scan result on both techniques, to confirm diagnosis of PD/DLB, significantly improved the specificity of DaTscan, from 38% to 75%, with no reduction in sensitivity.. Myocardial I-MIBG imaging provides complementary value to I-FP-CIT in the proper diagnosis, treatment plan, and differential diagnosis between PD and other forms of parkinsonism.

Topics: 3-Iodobenzylguanidine; Aged; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of. We included all PD (n = 154) and Control subjects (n = 62) with available. Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p <  0.05). While lower putaminal uptake on the contralateral side to clinically more affected side was associated with higher MDS-UPDRS III score (p = 0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p = 0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p = 0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p = 0.002 to 0.03). REM sleep behaviour disorder screening questionnaire was associated with lower. In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal

Topics: Adult; Aged; Brain; Case-Control Studies; Cohort Studies; Disease Progression; Female; Humans; Image Interpretation, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson's disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson's Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD.. We included 37 SWEDD cases (mean age 60 years, 33 % female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction.. PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p < 0.0001). PD group also showed lower binding in the thalamus relative to controls (p = 0.007). Receiver operating characteristics (ROC) area under the curve (AUC) did not show a significant difference when using extrastriatal region in addition to striatal ROIs for the separation of SWEDD and PD (95 % ROC-AUC for both methods, p = 0.52). In addition, striatal [123I]FP-CIT binding contralateral to the clinically more affected side was usually lower for PD (> 75 %) but not for SWEDD (< 49 %, p < 0.002). No significant difference regarding [123I]FP-CIT binding was observed between SWEDD and controls.. These findings corroborate the view that SWEDD cases represent a heterogeneous group of conditions not involving dopaminergic and serotonergic terminals. Further studies are warranted to be assessed whether using extrastriatal [123I]FP-CIT evaluation can be of help in the assessment of degenerative parkinsonism.

Topics: Case-Control Studies; Corpus Striatum; Disease Progression; Dopamine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Activity; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

It has been reported that early onset Parkinson's Disease (PD) patients have a less profound dopaminergic degeneration. The aim of the current study was to determine whether there are longitudinal differences in dopaminergic denervation [signal reduction in 123I-FP-CIT SPECT] in early versus mid and late onset PD.. DaTSCAN (123I-FP-CIT SPECT) imaging was acquired at Parkinson's Progression Markers Initiative (PPMI) imaging centers and sent to the imaging core for calculation of striatal binding ratios. Data from the PPMI database of 58 early de novo PD patients (age ≤ 50 years) were compared to those of 362 mid and late onset PD patients (age > 50 years).. Although raw striatal binding ratios were higher in early onset versus mid/late onset PD, especially on the ipsilateral side, such differences were not observed, and were in fact reversed in the contralateral putamen, after age correction. The rate of signal decline was similar between the two groups. Interestingly, based on both raw and age-adjusted data, caudate nucleus and putamen asymmetry (contralateral/ipsilateral ratio) was more pronounced in early onset PD. Striatal asymmetry also significantly correlated with age at onset as a continuous variable.. Early onset PD patients exhibited similar rates of decline of dopaminergic denervation compared to mid/late onset PD. These results are not supportive of a more benign disease in this subgroup. The more pronounced asymmetry in early onset PD may however signify a qualitatively different pattern of neurodegeneration compared to mid/late onset PD.

Topics: Aged; Caudate Nucleus; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Early Diagnosis; Female; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's Disease (PD) is a common neurodegenerative disorder, characterized by a progressive loss of dopaminergic neurons and whose cause remains unclear. Brain-Derived Neurotrophic factor (BDNF) is a protein involved in dopaminergic cells survival. Previous studies have shown decreased serum BDNF levels in PD patients.. The aim of the study was to evaluate serum BDNF levels in a group of recently diagnosed non-medicated PD patients and its relationship with the nigrostriatal system degeneration using I-123-FP-CIT.. 30 recently diagnosed, unmedicated PD patients were included in this study. Serum BDNF levels were measured twice using a sandwich enzyme linked immunoabsorbent assay and compared with levels of 27 unrelated Caucasian healthy adults. A I-123-FP-CIT SPECT was performed in all PD Patients in order to assess the association between serum BDNF levels and I-123-FP CIT uptake in several brain areas using a volumetric semi-automatic method.. PD patients showed lower serum BDNF levels (Median = 49.61, IQ range: 43.55 to 61.82) than the controls (Median = 68.82, IQ range: 51.87 to 88.14) (U = 211.00, z = -3.10, p = 0.002). BDNF levels in PD patients correlated with both caudate (Spearman r = 0.58, p = 0.001 for ispilateral and r 0.55, p = 0.002 for contralateral) and putamen (Spearman r = 0.68, p < 0.001 for ipsilateral and r = 0.80, p < 0.001 for contralateral) I-123-FP-CIT uptake ratios.. Serum BDNF levels were lower in recently diagnosed, untreated PD patients compared to controls. These lower levels were significantly correlated with the I-123-FP-CIT uptake ratios.

Topics: Adult; Aged; Brain-Derived Neurotrophic Factor; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of. We included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants.. This study provides evidence of a major extrastriatal

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; Lewy Body Disease; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders; Serotonin Plasma Membrane Transport Proteins; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

Idiopathic Parkinson's disease (PD) is characterized by clinical motor symptoms including hypokinesia, rigidity and tremor. In addition to the movement disorder, cognitive deficits are commonly described. In the present study, we applied FP-CIT SPECT to investigate the impact of nigrostriatal dopaminergic degeneration on cognitive function in PD patients.. Fifty-four PD patients underwent [. In the CERAD testing, PD patients exhibited deficits in the domains of semantic memory, attention, visuospatial function, non-verbal memory and executive function. After correction for multiple testing, the performance of the subtests Figure Recall and Trail-Making Test A correlated significantly with FP-CIT uptake into the ipsilateral executive subregion. The performance of the subtest Figure Saving correlated significantly with FP-CIT uptake into the contralateral executive subregion.. The significant correlation between cognitive function and density of nigrostriatal dopamine transporters, as assessed by FP-CIT SPECT, indicate that striatal dopaminergic pathways-primarily the executive striatal subregion-are relevant to cognitive processing in PD.

Topics: Cognition; Corpus Striatum; Female; Humans; Male; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Striatal dopamine deficits play a key role in the pathogenesis of Parkinson's disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component.. To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD.. We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups.. Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens.. This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Topics: Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Tropanes

To test the hypothesis that REM sleep behavior disorder (RBD) in early Parkinson's disease (PD) predicts rapid progression of dopaminergic denervation.. 123I-FP-CIT single photon emission computed tomography (SPECT) scans were performed sequentially at baseline, 1 year, 2 years, and 4 years in 416 de novo patients with PD. RBD screening questionnaire scores >5 at baseline placed the participant in the likely-RBD group. Temporal changes in the specific binding ratio (SBR; caudate, putamen. sum of both, striatum) were compared between the likely-RBD and the non-likely-RBD groups for more or less affected striatum with a repeated measure ANOVA.. Likely-RBD was reported in 37.7% of the drug-naïve PD patients at baseline. The likely-RBD and non-likely-RBD groups did not have significant differences in the baseline clinical features including gender, age, disease duration, UPDRS motor score, and striatal SBR. Striatal SBR decreased significantly over four years in both groups (P < .001). In the analysis of a more affected striatum, striatal SBR decreased significantly faster in the likely-RBD group than in the non-likely-RBD group (P < .05 for all), whereas it was not statistically significant for the less affected striatum. The mean striatal SBR value (mean value of both striata), especially the caudate SBR, indicated greater acceleration of denervation in the likely-RBD group than in the non-likely-RBD group over time (P < .05).. Likely-RBD in PD predicts accelerating dopaminergic denervation, thereby implicating it as a marker for a poor prognosis or distinctive subtype in PD.

Topics: Aged; Caudate Nucleus; Cohort Studies; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; REM Sleep Behavior Disorder; Tomography, Emission-Computed, Single-Photon; Tropanes

To elucidate longitudinal changes in the dopamine transporter (DAT) availability in association with the prodromal markers in idiopathic REM sleep behavior disorder (iRBD), we analyzed a longitudinal prospective iRBD cohort data.. The study cohort consisted of patients with iRBD, individuals with Parkinson disease (PD), and healthy controls. All participants were evaluated for olfaction, neuropsychological tests, and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale and underwent. DAT patterns in patients with iRBD with baseline hyposmia, constipation, and mild parkinsonian signs distributed toward the PD pattern and clearly distinguished from the healthy control pattern. The DAT pattern moved toward the PD pattern over time in some patients with iRBD during the follow-up, and baseline hyposmia was the only biomarker significantly associated with this change. Baseline PD pattern of DAT predicted 58% of disease converters (hazard ratio 4.95 [95% confidence interval 1.16-21.08]). The combination of hyposmia and baseline PD pattern of DAT predicted 67% of the conversion (hazard ratio 7.89 [confidence interval 1.85-33.69]). The estimated sample size required for a simulated neuroprotective clinical trial was 63 per group when the annual change of DAT pattern was used as an outcome in the subgroup with baseline DAT PD pattern and hyposmia, which is the smallest number reported so far.. Baseline and longitudinal monitoring of the DAT pattern can be a useful biomarker in identifying individuals with a high risk of disease conversion and in selecting the potential population for clinical trials in iRBD.

Topics: Aged; Anosmia; Biomarkers; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Principal Component Analysis; REM Sleep Behavior Disorder; Tropanes

Dopamine transporter SPECT is an established method to investigate nigrostriatal integrity in case of clinically uncertain parkinsonism.. The present study explores whether a data-driven analysis of [123I]FP-CIT SPECT is able to stratify patients according to mortality after SPECT.. Patients from our clinical registry were included if they had received [123I]FP-CIT SPECT between 10/2008 and 06/2016 for diagnosis of parkinsonism and if their vital status could be determined in 07/2017. Specific binding ratios (SBR) of the whole striatum, its asymmetry (asymmetry index, AI; absolute value), and the rostrocaudal gradient of striatal binding (C/pP: caudate SBR divided by posterior putamen SBR) were used as input for hierarchical clustering of patients. We tested differences in survival between these groups (adjusted for age) with a Cox proportional hazards model.. Data from 518 patients were analyzed. Median follow-up duration was 3.3 years [95% C.I. 3.1 to 3.7]. Three subgroups identified by hierarchical clustering were characterized by relatively low striatal SBR, high AI, and low C/pP (group 1), low striatal SBR, high AI, and high C/pP (group 2), and high striatal SBR, low AI, and low C/pP (group 3). Mortality was significantly higher in group 1 compared to each of the other two groups (p = 0.029 and p = 0.003, respectively).. Data-driven analysis of [123I]FP-CIT SPECT identified a subgroup of patients with significantly increased mortality during follow-up. This suggests that [123I]-FP-CIT SPECT might not only serve as a diagnostic tool to verify nigrostriatal degeneration but also provide valuable prognostic information.

Topics: Adult; Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Prognosis; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Female; Hamstring Muscles; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Putamen; Thigh; Tremor; Tropanes

Serotonergic raphe nuclei dysfunction has been documented in Parkinson's disease, both in pathological and neuroimaging studies, and has been associated with scores of tremor and non-motor symptoms. However, no in vivo longitudinal investigations have been conducted to assess the rate of decline of raphe serotonin transporter availability in the early stages of the disease.. To measure the rate of decline of raphe serotonin transporter availability over a two-year interval in patients with recently diagnosed disease and its association with non-motor symptoms over time.. Baseline and two-year follow-up. A 16.6 ± 20.9% (mean ± SD) reduction in raphe serotonin transporter availability was found from baseline to two-year follow-up in the entire cohort. No differences in progression were found between tremor dominant and postural instability/gait difficulty phenotypes. At follow-up 34.1% of patients showed a moderate-to-severe reduction of raphe serotonin transporter availability with respect to the controls' mean. We did not find any significant correlation between raphe serotonin transporter availability and scores of depression, excessive daytime sleepiness and REM sleep behaviour disorder.

Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; REM Sleep Behavior Disorder; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD.. Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated.. One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = -0.440, P < 0.001).. Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [F]FP-CIT PET/CT.

Topics: Adult; Aged; Aged, 80 and over; Bilirubin; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Positron Emission Tomography Computed Tomography; Retrospective Studies; Tropanes; Young Adult

We studied whether

Topics: Adult; Aged; Aged, 80 and over; Cognition; Corpus Striatum; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Using dual time F-18 FP-CIT, we evaluated cortical perfusion, striatal binding and neuropsychological performance simultaneously in Parkinson disease (PD) with and without mild cognitive impairment (MCI), to investigate neural correlates between caudate and frontal cortex.. According to the neuropsychological scores, subjects were classified into 26 healthy controls (HC), 38 PD-MCI (executive) (PE), 24 PD-MCI (non-executive) (PN) and 21 PD (motor) (PM). Scans were acquired at 10 minutes and 2 hours. Group differences of early perfusion and delayed binding were compared using SPM and volume of interest method. The relationships between neuropsychological variables and the striatal binding were investigated with correlation and regression analysis.. Compared with PM, PE showed decreased prefrontal perfusion and binding of both caudates (right: P=0.0010, left: P=0.014), but not of both putamens. Compared with PN, PE showed decreased binding of both caudates (right: P=0.001, left: P=0.005), but not in both putamens. Binding of both caudates correlated with the Stroop z-score, but not of both putamens. Executive score was a contributing factor to binding of the caudate, and not the putamen.. PE showed decreased prefrontal perfusion and caudate binding, supporting neural correlates between the caudate and the prefrontal cortex. Dopaminergic binding of the caudate, but not of the putamen, was related to executive scores. Caudate hypofunction was specific to executive domain. This is the first study that elucidated the clinical use of dual time F-18 FP-CIT for integrative evaluation of cognitive and motor function in PD.

Topics: Aged; Case-Control Studies; Cerebral Cortex; Cognition; Female; Humans; Male; Middle Aged; Motor Activity; Neostriatum; Parkinson Disease; Positron Emission Tomography Computed Tomography; Time Factors; Tropanes

Neuromelanin magnetic resonance imaging (NmMRI) and. To determine whether a multiparametric scoring system (MSS) could improve accuracy compared to each parameter of DAT-SPECT and NmMRI in differentiating PD from NDPS.. A total of 49 patients, including 14 with NDPS, 30 with PD, and five with atypical parkinsonian disorder (APD) underwent both NmMRI and DAT-SPECT and were evaluated. The average (Ave) and the asymmetry index (AI) were calculated in the substantia nigra compacta area (SNc-area), SNc midbrain-tegmentum contrast ratio (SNc-CR), and specific binding ratio (SBR). Cut-off values were determined, using receiver operating characteristic (ROC) analysis, for the differentiation of PD from NDPS on the statistically significant parameters. All cases were scored as either 1 (PD) or 0 (NDPS) for each parameter according to its threshold. These individual scores were totaled for each case, yielding a combined score for each case to obtain a cut-off value for the MSS.. The Ave-SNc-area, Ave-SNc-CR, and Ave-SBR in PD were significantly lower than those in NDPS. The AI-SNc-area and AI-SBR in PD were significantly higher than those in NDPS. Of the five parameters, the highest accuracy was 93% for the Ave-SNc-area. For the MSS, a cut-off value of 3 was the accuracy of 96%. Besides, no significant difference was observed between PD and APD on all parameters.. An MSS has comparable or better accuracy compared to each parameter of DAT-SPECT and NmMRI in distinguishing PD from NDPS.

Topics: Aged; Aged, 80 and over; Biomarkers; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Melanins; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Quantitative assessment of dopamine transporter imaging can aid in diagnosing Parkinson disease (PD) and assessing disease progression in the context of therapeutic trials. Previously, the software program SBRquant was applied to

Topics: Case-Control Studies; Disease Progression; Humans; Image Processing, Computer-Assisted; Nortropanes; Parkinson Disease; Software; Tomography, Emission-Computed, Single-Photon

Patients with Parkinson's disease (PD) present a variety of non-motor symptoms. However, it remains unclear whether dopamine depletion is related to non-motor symptoms, and which non-motor symptoms are significantly dependent on dopaminergic deficit.. Forty-one patients with PD who underwent positron emission tomography imaging of dopamine transporters (DATs) were recruited for this study. The striatum was divided into 12 subregions, and DAT activity, as striatal dopaminergic concentration, was calculated in each subregion. In addition to measuring motor symptoms using the Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), various non-motor symptoms were assessed using the Montreal cognitive assessment, frontal assessment battery, Beck depression inventory (BDI), Beck anxiety inventory, PD sleep scale (PDSS), PD fatigue scale, and non-motor symptoms scale (NMSS) for PD.. For simple linear regression analyses, dopaminergic depletion in all striatal subregions was negatively correlated with the UPDRS-III score. The most relevant non-motor symptom assessment related to dopaminergic loss in the 12 subregions was NMSS, followed by BDI and PDSS. However, following multiple linear regression analyses, dopaminergic depletion in the 12 striatal subregions was not related with any of the non-motor symptoms. Conversely, dopaminergic deficit in the right anterior and posterior putamen was associated with the UPDRS-III score.. Striatal dopaminergic depletion was not significantly correlated with any of the various non-motor symptoms in PD. Our findings suggest that non-dopaminergic systems are significantly implicated in the pathogenesis of non-motor symptoms in patients with PD.

Topics: Aged; Antiparkinson Agents; Brain Mapping; Corpus Striatum; Dopamine; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Parkinson Disease; Positron-Emission Tomography; Psychiatric Status Rating Scales; Radiopharmaceuticals; Retrospective Studies; Severity of Illness Index; Tropanes

Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA.. We performed [. The two PD patients and two of the four clinically unaffected carriers showed decreased [. We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [

Topics: Aged; Aged, 80 and over; Asian People; Brain; Exons; Family; Female; Gene Deletion; Glucosylceramidase; Humans; Iofetamine; Japan; Leukocytes; Male; Middle Aged; Neuroimaging; Parkinson Disease; Pedigree; Radiopharmaceuticals; Reverse Transcriptase Polymerase Chain Reaction; Tomography, Emission-Computed, Single-Photon; Tropanes

In patients with Parkinson's disease (PD), abnormal activations of nociceptive brain areas and lowered pain thresholds were reported, probably reflecting a central modification of pain processing. The aim of this study was to investigate the possible correlation between the striatal and extrastriatal dopaminergic system and pain threshold in PD patients. We included 25 PD patients with various intensities of central pain (visual analog scale). Subjective pain threshold (thermotest) and a motor examination (UPDRS III) were performed. Patients underwent SPECT imaging with [

Topics: Aged; Brain; Dopamine; Female; Humans; Male; Middle Aged; Pain; Pain Threshold; Parkinson Disease; Pilot Projects; Tomography, Emission-Computed, Single-Photon; Tropanes

Motor but also non-motor effects are modulated by dopamine (DA) in Parkinson's disease (PD). Impaired inhibition has been related to dopamine overdosing of the associative striatum. We compared effects of dopaminergic medication on inhibitory control in patients with young (age at onset <50 years, YOPD) and late onset PD (LOPD) and related them to nigrostriatal degeneration.. Patients made more errors ON compared to OFF in the global NoGo. This DA effect on global NoGo errors correlated with disease duration (r = 0.489, p = 0.010). YOPD made more errors in the specific NoGo ON-OFF compared to LOPD (p = 0.015). YOPD showed higher associative-to-sensorimotor DAT ratios compared to LOPD (p < 0.001). Neuro-computational modeling revealed DA overdosing of the associative striatum in YOPD resulting in excess activation of the direct basal ganglia pathway triggering incorrect responses.. Depending on the age of symptom onset, DA differentially modulated inhibition in PD with detrimental effects on specific NoGo performance in YOPD but increased performance in LOPD. YOPD showed relatively less degeneration in the associative striatum suggesting DA overdosing that is supported by our neuro-computational model. Reduced inhibition in the global NoGo condition suggests different pathway activation.

Topics: Adult; Age of Onset; Aged; Computer Simulation; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Inhibition, Psychological; Male; Middle Aged; Parkinson Disease; Psychomotor Performance; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using

Topics: Aged; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Female; Hippocampus; Humans; Hypothalamus; Lewy Body Disease; Male; Middle Aged; Neostriatum; Parkinson Disease; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins; Thalamus; Tomography, Emission-Computed, Single-Photon; Tropanes

Little is known regarding the clinical relevance or neurobiology of subtle motor disturbance in Alzheimer's disease (AD). This study aims to investigate the patterns of striatal. Patients with ADCI with mild parkinsonism exhibited decreased DAT availability in the caudate that was intermediate between healthy controls and patients with DLB. The DAT availability in other striatal subregions, including the posterior putamen, did not differ between the ADCI with parkinsonism and healthy control groups. The ROC analysis showed that DAT availability of all striatal subregions, especially the whole striatum, had a fair discriminatory power. Parkinsonian motor severity did not correlate with the striatal DAT availability in ADCI with parkinsonism.. The present study demonstrated that patients with ADCI with mild parkinsonism had distinct DAT scan patterns and suggests that parkinsonism is associated with the extranigral source of pathology.

Topics: Aged; Alzheimer Disease; Corpus Striatum; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tropanes

Speech difficulties are a common debilitating feature of Parkinson's disease and we aimed to investigate whether speech difficulties are associated with striatal dopaminergic deficits and faster disease progression.. Using the Parkinson's Progression Markers Initiative database, 143 early de novo Parkinson's disease patients with speech difficulties were identified and matched 1:1 with 143 Parkinson's disease patients without speech difficulties for age, disease duration and motor symptom severity. We investigated differences in clinical features and striatal [. Speech difficulties were more common in patients with an akinetic-rigid motor phenotype compared to those with a tremor-dominant phenotype. Parkinson's disease patients with speech difficulties had lower resting tremor (P = 0.027), higher autonomic dysfunction (P = 0.034), increased daytime sleepiness (ESS; P = 0.048), and a higher prevalence of REM sleep behaviour disorder (RBD) symptoms (P = 0.007) compared to those without speech difficulties. Parkinson's disease patients with speech difficulties had significantly lower [. Speech difficulties are associated with greater autonomic dysfunction, sleep disturbances and striatal dopaminergic deficit, and can serve as a predictor of faster cognitive decline in early Parkinson's disease.

Topics: Aged; Autonomic Nervous System Diseases; Cognitive Dysfunction; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; REM Sleep Behavior Disorder; Sleepiness; Speech Disorders; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Although not typical of Parkinson's disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using. Patients with PD and healthy controls were identified from the Parkinson's Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as. At baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).. Early significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.

Topics: Aged; Case-Control Studies; Caudate Nucleus; Cognitive Dysfunction; Depression; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Fluctuating body weight is a commonly reported nonmotor feature in patients with Parkinson's disease (PD). We hypothesised that striatal dopamine transporter (DAT) density at the time of diagnosis might play an important role in weight regulation in patients with PD. DAT density was measured from

Topics: Adult; Aged; Aged, 80 and over; Caudate Nucleus; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Parkinson Disease; Prognosis; Putamen; Sex Factors; Tomography, Emission-Computed, Single-Photon; Tropanes; Weight Gain; Weight Loss

To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson disease (PD).. Using data from 335 patients with PD in the Parkinson's Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by. GRS1 and GRS2 were correlated with younger age at onset in patients with PD (GRS1, Spearman ρ = -0.128,. Our results suggest that genetic factors for PD risk may have heterogeneous effects on striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD progression-specific GRS may be useful in predicting disease progression in patients.

Topics: Adult; Aged; Caudate Nucleus; Corpus Striatum; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Putamen; Tropanes

Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Melanins; Middle Aged; Parkinson Disease; Retrospective Studies; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD), yet the neural mechanisms have been scarcely investigated. Disturbances in dopaminergic and serotonergic signalling may play a role in its pathophysiology.. We studied the association between anxiety symptoms, measured with an affective subscale of the Beck Anxiety Inventory, and (extra)striatal. Severity of anxiety symptoms showed a significant negative association with. This study shows that higher levels of anxiety in patients with PD are associated with lower thalamic

Topics: Aged; Anxiety; Brain; Brief Psychiatric Rating Scale; Corpus Striatum; Cross-Sectional Studies; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD.. Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders.. Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score.. The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

Topics: Aged; Aggression; Anxiety; Apathy; Appetite; Atrophy; Brain; Cerebral Cortex; Depression; Dopamine Plasma Membrane Transport Proteins; Female; Fluorine Radioisotopes; Humans; Inhibition, Psychological; Irritable Mood; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Nucleus Accumbens; Organ Size; Parkinson Disease; Positron-Emission Tomography; Tropanes

In this study, the prevalence of abnormality in putative nigrosome 1 and nigrosome 4 (N1 and N4, respectively) was investigated in early versus late-stage idiopathic Parkinson's disease (IPD) patients. A total of 128 IPD patients (early stage[n = 89]; late stage[n = 39]) and 15 healthy subjects were scanned for high-resolution (0.5 × 0.5 × 1.0 mm

Topics: Aged; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Substantia Nigra; Tropanes

Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset.. From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups.. The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033).. This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

Topics: Dopamine; Dopamine Plasma Membrane Transport Proteins; Dyskinesias; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Positron Emission Tomography Computed Tomography; Prognosis; Synapses; Time Factors; Tropanes

To determine whether there were differences in clinical outcomes for ioflupane I. We performed a case-control study among patients presenting to the Emergency Room (ER) during 2006-2013 with mTBI (cases, n = 34) or without mTBI (controls, n = 33). We performed clinical and imaging measurements in cases and controls at least 1-year post-presentation to the ER (average three years four months).. All DaTscans obtained were qualitatively normal. There were no qualitative DaTscan differences between cases and controls. There was, however, a significant increase in caudate asymmetry in controls versus cases (p = 0.02), but this finding was no longer significant after correction for multiple comparisons. There was a suggestion of a trend of poorer clinical score test measures among those with mTBI, although the overall mean score difference between cases and controls was not clinically significant.. Our small study does not provide support for DaTscan changes suggestive of PD in the one to seven years following mTBI. A trend towards poorer clinical measures was seen but was not clinically relevant in our small sample. Further work in a large population is necessary to support these findings.

Topics: Adolescent; Adult; Aged; Biomarkers; Brain; Brain Concussion; Case-Control Studies; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Young Adult

Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects.. Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database ( www.ppmi-info.org/data ). The study population consisted of healthy controls with screening. Totally, 181 healthy subjects (117 male, 64 female) with. Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects.. • Olfactory dysfunction in Parkinson's disease is prodromal to other symptoms. • The availability of dopamine transporter showed a reduction with ageing. • Olfactory function is associated with the availability of dopamine transporter.

Topics: Adult; Aged; Caudate Nucleus; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Putamen; Reference Values; Smell; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopamine transporter SPECT imaging is a valuable tool to estimate the integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms. Evidence about SPECT differential pattern between parkinsonian and cerebellar forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at assessing whether MSA-P and MSA-C variants have a distinct semiquantitative I-FP-CIT SPECT pattern.. We studied a unicentric 13-year (2003-2016) retrospective cohort of subjects with possible or probable MSA and scanned with the same acquisition and reconstruction SPECT protocol. Age-dependent semiquantitative reference limits for striatal volumes of interest, asymmetry indices, and caudate/putamen ratio were previously established with a percentile approach on a cohort of subjects with nondegenerative conditions and normal visual scan.. Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA-C) were identified (mean age, 68.2 ± 10.1 years; male/female ratio 1.00; disease duration, 2.5 ± 2.2 years; Movement Disorders Society Unified Parkinson's Disease Rating Scale III score, 33.8 ± 12.4). The MSA-P subjects exhibited lower uptake values for all volumes of interest, for example, striatal uptake on the more affected side (1.10 ± 0.51) compared with MSA-C (2.30 ± 0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 ± 24.8 vs 6.3 ± 4.5, P = 0.028) and caudate/putamen ratio (2.26 ± 1.23 vs 1.13 ± 0.17, P = 0.00148).. The MSA-P and MSA-C subjects exhibited significantly distinct semiquantitative SPECT pattern with severe uptake impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C. Clinical distinction of these 2 phenotypical entities is necessary in order to evaluate SPECT potential to discriminate between degenerative parkinsonisms.

Topics: Adult; Aged; Aged, 80 and over; Cerebellum; Cohort Studies; Diagnosis, Differential; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Retrospective Studies; Sensitivity and Specificity; Tropanes

This work aimed to assess the potential of a set of features extracted from [. Seven features were computed from each brain hemisphere: five standard features related to uptake ratios on the striatum and two features related to the estimated volume and length of the striatal region with normal uptake. The features were tested on a dataset of 652 [. Cross-validation results based on SVM have shown that, individually, the features that generated the highest accuracies were the length of the striatal region (96.5%), the putaminal binding potential (95.4%) and the striatal binding potential (93.9%) with no statistically significant differences among them. The highest classification accuracy was obtained using all features simultaneously (accuracy 97.9%, sensitivity 98% and specificity 97.6%). Generally, slightly better results were obtained using the SVM with no statistically significant difference to the other classifiers for most of the features.. The length of the striatal region uptake is clinically useful and highly valuable to confirm dopaminergic degeneration "in vivo" as an aid to the diagnosis of Parkinson's disease. It compares fairly well to the standard uptake ratio-based features, reaching, at least, similar accuracies and is easier to obtain automatically. Thus, we propose its day to day clinical use, jointly with the uptake ratio-based features, in the computer-aided diagnosis of dopaminergic degeneration in Parkinson's disease.

Topics: Aged; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Parkinson Disease; Sweden; Tomography, Emission-Computed, Single-Photon; Tropanes

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinson's disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinson's Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p < 0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p < 0.001).

Topics: Age of Onset; Antiparkinson Agents; Coffee; Corpus Striatum; Diet; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Multivariate Analysis; Parkinson Disease; Radiopharmaceuticals; Retrospective Studies; Risk Factors; Severity of Illness Index; Smoking; Tomography, Emission-Computed, Single-Photon; Tropanes

Rest tremor is one of the cardinal signs of Parkinson's disease. Kinetic and postural tremors may also occur. The coexistence of these three types of tremor at disease onset and their subsequent progression could have important clinical and therapeutic implications but remain to be fully elucidated. We aimed to: (i) evaluate prevalence and progression of these three types of tremor in early stages of the disease; and (ii) investigate longitudinally the relationship between dopaminergic and serotonergic terminal dysfunction, rest tremor severity and its response to dopaminergic therapy. The Parkinson's Progressive Markers Initiative database provided the baseline and 2-year follow-up clinical ratings and 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodophenyltropane (123I-FP-CIT) single photon emission computed tomography images for this study. 123I-FP-CIT measured putamen dopamine transporter and median raphe serotonin transporter availability. A raphe/putamen uptake ratio was calculated for each patient as an index of relative involvement of these structures. Clinical analysis of tremor was conducted on 378 patients: 87.8% presented with tremor at baseline; rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic tremors occurred in about 50% of patients at both baseline and follow-up. Over 20% of patients presenting with tremor did not exhibit a rest component at baseline. The number of patients with isolated rest tremor was halved at follow-up. In tremor predominant patients, rest tremor severity was inversely correlated with raphe serotonin transporter availability both at baseline and follow-up (baseline: constancy P < 0.05, tremor index P < 0.05; follow-up: amplitude P < 0.05, constancy P < 0.05, tremor index P < 0.05). In the entire cohort, more severe tremor scores correlated with lower raphe/putamen uptake ratio values, indicative of more severe raphe dysfunction (baseline: constancy P < 0.01, tremor index P < 0.05; follow-up: amplitude P < 0.01, constancy P < 0.001, tremor index P < 0.001). The percentage of improvement in rest tremor amplitude after acute dopaminergic therapy was smaller in patients with lower raphe/putamen uptake ratio values (P < 0.01). Rest tremor is the most represented type of tremor in early Parkinson's disease. However, postural and kinetic tremor can affect approximately half of these patients and can occur in absence of resting tremor. As disease progresses, both raphe sero

Topics: Adult; Aged; Aged, 80 and over; Brain; Disease Progression; Female; Humans; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Imaging studies are necessary prior to subthalamic deep brain stimulation (STN-DBS). Dopamine transporter (DAT) imaging is a powerful tool for visualizing dopamine terminals in the striatum, but its usefulness in STN-DBS is unclear. Here, we retrospectively investigated the relationship between motor symptoms and the specific binding ratio (SBR) on DAT imaging in patients with Parkinson's disease (PD). We included 23 consecutive patients (9 female; 14 male) who were evaluated for DBS eligibility between October 2013 and October 2014 and subsequently received bilateral STN-DBS. Correlation and simple regression analyses were performed on SBR values and clinical parameters before and after surgery. SBR value was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the "ON" state before surgery (r

Topics: Adult; Aged; Corpus Striatum; Deep Brain Stimulation; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Motor Activity; Parkinson Disease; Pilot Projects; Protein Binding; Regression Analysis; Statistics, Nonparametric; Subthalamic Nucleus; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of the present study was to determine the relation of urinary dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We therefore examined the relation of overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography (. Thirty-one untreated PD patients (12 men and 19 women with a mean age of 71.2 ± 6.7 years) were included in this study. Patients were evaluated with overactive bladder symptom score (OABSS) and divided into an OAB group and Non-OAB group. They underwent clinical assessments and. The results showed that UPDRS motor score (p = 0.01) and akinetic-rigid score (p = 0.002) were higher and that striatal DAT availability (p = 0.01) was lower in the OAB group than in the Non-OAB group. However, tremor score, age, and duration of PD showed no significant differences between the OAB group and Non-OAB group.. Urinary dysfunction in untreated PD is related with increase in motor symptoms (especially bradykinesia and axial symptoms) and reduction of striatal DAT availability.

Topics: Aged; Aged, 80 and over; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dyskinesias; Humans; Middle Aged; Parkinson Disease; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes; Urinary Bladder, Overactive

s: Over recent years there have been some conflicting reports upon the role of pallidal dopaminergic denervation in rest tremor in Parkinson's disease.. To clarify this issue we analyzed the clinical and 123I-FP-CIT SPECT data of a large cohort of early Parkinson's disease patients enrolled in the PPMI study.. Pallidal and striatal dopamine transporter uptake ratios were calculated in 382 patients (120 no-tremor, 60 tremor-dominant, and 202 indeterminate) and 150 controls. A region of interest (ROI) approach was used to estimate DAT uptake ratios from 123I-FP-CIT SPECT scans in the caudate nucleus, putamen, and globus pallidus after normalization to a DAT template. DAT uptake ratios for each region were compared between subgroups using ANCOVA and linear regression analyses were performed to evaluate the relationship between severity of rest tremor and regional DAT uptake ratios.. PD patients had significantly lower DAT uptake ratios in the pallidum, putamen and caudate as compared to healthy controls (p < 0.001). ANCOVA showed inter-PD subgroup differences in DAT uptake ratios in the putamen and pallidum (p < 0.05) after adjustment for age and disease duration, with post-hoc comparisons revealing significantly higher DAT uptake ratios for the tremor-dominant subgroup as compared to non-tremor and indeterminate subgroups (p < 0.016). There was no significant relationship between rest tremor severity and pallidal DAT either in the tremor-dominant subgroup or in the total PD population.. Pallidal dopaminergic denervation appears unrelated to rest tremor severity in early Parkinson's disease.

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Female; Globus Pallidus; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Weight loss in Parkinson's disease (PD) is associated with poorer clinical outcomes and rapid disease progression. However, it is unclear whether a longitudinal association between weight loss and striatal dopaminergic degeneration exists.. Using data from 171 PD patients in the Parkinson's Progression Markers Initiative (PPMI) cohort, we investigated longitudinal associations of change in body mass index (BMI) with striatal dopaminergic activity on. Our findings suggest a potential association between striatal dopaminergic activity with body weight or impairment in energy homeostasis. Body weight and its change may be a clinical biomarker reflecting striatal dopaminergic dysfunction in PD.

Topics: Aged; Body Mass Index; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neostriatum; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes; Weight Loss

To investigate the relationship between the sub-regional pattern of striatal dopamine depletion and cognitive impairment in early-stage Parkinson's disease (PD), and determine the effect of striatal dopamine density on cognitive prognosis.. Patients with drug-naïve non-demented PD were divided into mild cognitive impairment (PD-MCI; n = 129) and cognitively normal (PD-CogN; n = 182) groups. Using quantification of the dopamine transporter (DAT) availability in each striatal sub-region with. The PD-MCI group exhibited more severely decreased DAT availability in all the striatal sub-regions compared to the PD-CogN group, although there was no significant difference in PD duration. The DAT availability in the caudate, anterior putamen, and ventral striatum was directly associated with attention/working memory, frontal/executive, and visuospatial functions, while the DAT availability of the posterior putamen was not. However, the baseline DAT availability of the striatal sub-regions did not influence the cognitive decline or cognitive status in the longitudinal cognitive assessment.. Our results suggest that striatal DAT availability may determine MCI in patients with de novo PD. Dopamine loss in the associative and limbic striatum is closely linked to cognitive deficits in early-stage PD, although it does not affect cognitive prognosis.

Topics: Aged; Cognitive Dysfunction; Corpus Striatum; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Tropanes

Excessive daytime sleepiness (EDS) is one of the earliest and most common non-motor symptoms of PD, substantially impacting on patient's quality of life. Using the Parkinson's Progression Markers Initiative database, we performed a case-control study to investigate whether dopaminergic deficit is associated with the development of EDS using dopaminergic specific single photon emission computed tomography (SPECT) molecular imaging of dopamine transporters (DAT). We enrolled 84 early de novo PD patients with EDS and 84 without EDS, who were matched for age, gender, age of diagnosis, years of education and disease duration. We assessed and compared semi-quantified [

Topics: Aged; Caudate Nucleus; Disorders of Excessive Somnolence; Dopamine Agonists; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Protein Binding; Severity of Illness Index; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD.. We describe 5-year longitudinal change of the MDS-UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123-I Ioflupane striatal binding and correlation between the 2 measures.. A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS-UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for the change over time), with a steeper change in year 1. Dopaminergic therapy had a significant effect on the change of MDS-UPDRS. There was a significant longitudinal change in dopamine transporter binding in all striatal regions (P < .001). There was a significant but weak correlation between MDS-UPDRS and dopamine transporter binding at baseline and years 1, 2, and 4, but no correlation between the rate of change of the 2 variables.. We present 5-year longitudinal data on the change of the MDS-UPDRS and other clinical and dopamine transporter imaging outcome measures in early PD. These data can be used for sample size estimates for interventional studies in the de novo PD population. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Age Factors; Aged; Amyloid beta-Peptides; Cohort Studies; Corpus Striatum; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Peptide Fragments; tau Proteins

To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease.. We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline.. The presence of diabetes mellitus was associated with higher motor scores (. Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype.

Topics: Adult; Aged; alpha-Synuclein; Blood Glucose; Cognition Disorders; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Longitudinal Studies; Male; Middle Aged; Motor Disorders; Parkinson Disease; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson's disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging.. Data were obtained from the Parkinson's Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups.. There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI).. Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646-651).

Topics: Aged; Cognitive Dysfunction; Dopamine; Humans; Middle Aged; Neuropsychological Tests; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

We aimed to investigate the association between genetic factors of SNPs dopamine transporter (DAT) and serotonin transporter (SERT) availabilities in healthy controls.. The study population consisted of healthy controls with screening. One hundred sixty healthy controls (male 106, female 54, 61.0 ± 11.5 years) were included in this study. Sex difference did not exist in DAT availabilities of caudate nucleus (p = 0.5344), putamen (p = 0.5006), and striatum (p = 0.5056). However, male subjects had higher SERT availabilities of both midbrain (p = 0.0436), and pons (p = 0.0061). Therefore, we analyzed the effect of SNP on DAT availabilities of subjects in all, and that on SERT availabilities of males and females separately. None of 19 SNPs included in this study showed the effect on DAT availabilities. However, rs591323 in Fibroblast Growth Factor 20 on chromosome 8 had a significant impact on SERT availability of both midbrain (p = 0.0056) and pons (p = 0.0007).. SNP rs591323 of risk loci for Parkinson's disease is associated with SERT availability of healthy male subjects.

Topics: Brain; Brain Mapping; Dopamine Plasma Membrane Transport Proteins; Female; Fibroblast Growth Factors; Humans; Male; Middle Aged; Parkinson Disease; Polymorphism, Single Nucleotide; Radiopharmaceuticals; Serotonin Plasma Membrane Transport Proteins; Sex Characteristics; Tomography, Emission-Computed, Single-Photon; Tropanes

The role of nuclear imaging in predicting Parkinson's disease (PD) progression is unclear. This study investigated whether the degree of reduced striatal dopamine transporter binding at diagnosis of PD predicts later motor complications and time to disease progression.. We retrospectively studied 41 patients with early PD who underwent. Logistic regression models controlling for age at diagnosis, sex, disease duration, and L-dopa dose revealed that. Our results suggest that a more severe depletion of presynaptic dopamine in early PD is a bad prognostic sign in terms of FOG development. These findings, if replicated, may point to dopaminergic transmission as part of the mechanism underlying FOG in PD.

Topics: Aged; Brain; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dyskinesias; Female; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Parkinson Disease; Prognosis; Radiopharmaceuticals; Retrospective Studies; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Dopamine; Humans; Lewy Body Disease; Neurodegenerative Diseases; Parkinson Disease; Presynaptic Terminals; Tomography, Emission-Computed, Single-Photon; Tropanes

The objective of this study was to identify the extent to which artificial intelligence could be used in the diagnosis of Parkinson's disease from ioflupane-123 (¹²³I) single-photon emission computed tomography (SPECT) dopamine transporter scans using transfer learning.. A data set of 54 normal and 54 abnormal ¹²³I SPECT scans was amplified 44-fold using a process of image augmentation. This resulted in a training set of 2376 normal and 2376 abnormal images. This was used to retrain the top layer of the Inception v3 network. The resulting neural network functioned as a classifier for new ¹²³I SPECT scans as either normal or abnormal. A completely separate set of 45 ¹²³I SPECT scans were used for final testing of the network.. The area under the receiver-operator curve in final testing was 0.87. This corresponded to a test sensitivity of 96.3%, a specificity of 66.7%, a positive predictive value of 81.3% and a negative predictive value of 92.3%, using an optimum diagnostic threshold.. This study has provided proof of concept for the use of transfer learning, from convolutional neural networks pretrained on nonmedical images, for the interpretation of ¹²³I SPECT scans. This has been shown to be possible in this study even with a very small sample size. This technique is likely to be applicable to many areas of diagnostic imaging.

Topics: Image Processing, Computer-Assisted; Machine Learning; Neural Networks, Computer; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

To investigate whether REM sleep behavior disorder (RBD) is associated with worse motor and cognitive decline in Parkinson disease (PD) METHODS: Four-hundred twenty-one drug-naive patients with early-stage PD and 196 controls without PD were included in this study. All participants underwent a [. At cross-sectional analyses, patients with PD and probable RBD (PD-RBD) had lower CSF β-amyloid 1-42 (Aβ. The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology. Our findings provide an important direction toward understanding phenotypes and their prognosis in PD.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Amyloid beta-Peptides; Brain; Cognition Disorders; Cohort Studies; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Peptide Fragments; REM Sleep Behavior Disorder; Severity of Illness Index; Statistics, Nonparametric; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Discrete patterns of progression have been suggested for patients with Parkinson disease and presenting tremor dominant (TD) or postural instability gait disorders (PIGD). However, longitudinal prospective assessments need to take into consideration the variability in clinical manifestations and the evidence that only 40% of initially classified PIGD remain in this subtype at subsequent visits.. We analyzed clinical progression of PIGD compared to TD using longitudinal clinical data from the PPMI. Given the reported instability of such clinical classification, we only included patients who were reported as PIGD/TD at each visit during the 4-year observation. We used linear mixed-effects models to test differences in progression in these subgroups in 51 dependent variables.. There were 254 patients with yearly assessment. The number of PIGD was 36/254 vs 144/254 TD. PIGD had more severe motor disease at baseline but progressed faster than TD only in three non-motor items of the MDS-UPDRS: cognitive impairment, hallucinations, and psychosis plus features of DDS. Our analysis also showed in PIGD faster increase in the average time with dyskinesia.. PIGD are characterized by more severe disease manifestations at diagnosis and greater cognitive progression, more frequent hallucinations, psychosis as well as features of DDS than TD patients. We interpret these findings as expression of greater cortical and subcortical involvement in PIGD already at onset. Since PIGD/TD classification is very unstable at onset, our analysis based on stricter definition criteria provides important insight for clinical trial stratification and definition of related outcome measures.

Topics: Adult; Aged; Cognition Disorders; Databases, Factual; Disease Progression; Female; Gait Disorders, Neurologic; Humans; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Nortropanes; Parkinson Disease; Psychiatric Status Rating Scales; Severity of Illness Index; Surveys and Questionnaires

To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD).. Approximately 634 patients with drug-naive PD who underwent F-FP-CIT PET scans were followed up for at least 2 years. After quantifying dopamine transporter (DAT) availability in each striatal subregion, the patterns of striatal dopamine depletion of each patient were assessed based on (1) the degree of dopamine loss in the other striatal subregions compared to the posterior putamen (inter-subregional ratio [ISR]) and (2) the interhemispheric asymmetry of dopamine loss in the posterior putamen (asymmetry index [AI]). According to their patterns, we assessed the longitudinal changes in L-dopa-equivalent doses and L-dopa-induced dyskinesia (LID)-free times using the linear mixed model and Cox regression model, respectively.. There was no significant correlation between the ISR and AI values (Pearson correlation coefficient, 0.150). The linear mixed model showed that higher AI values were associated with slower longitudinal increases in L-dopa-equivalent dose across time (P = 0.003), whereas ISR values were not (P = 0.154). The Cox regression model demonstrated that higher ISR values were associated with early development of LID (hazard ratio, 1.693; P = 0.010), whereas AI values were not (P = 0.269).. The present study demonstrated that the pattern of anterior-to-posterior gradient and right-to-left asymmetry of striatal DAT availability predicted the development of LID and increasing doses of dopaminergic medications.

Topics: Biomarkers; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Levodopa; Male; Middle Aged; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Prognosis; Tropanes

The aim of this study was to study the significance of combining iodine-123-cardiac metaiodobenzylguanidine scintigraphy (I-MIBG scintigraphy) and iodine-123-ioflupane (I-ioflupane) dopamine transporter scintigraphy (I-ioflupane scintigraphy) in patients suspected of having Parkinson's disease (PD).. We carried out a retrospective study from April 2014 to December 2015 in 48 patients suspected of having new-onset PD who underwent both I-MIBG and I-ioflupane scintigraphies within 3 months. Cases included 37 patients diagnosed as having PD. Controls included 11 patients who had never been diagnosed as having PD or other diseases showing parkinsonism. The cutoff for diagnosing PD was a heart to mediastinum ratio (H/M ratio) of less than or equal to 2.2 for I-MIBG scintigraphy in the delayed phase and a specific binding ratio (SBR) of less than or equal to 3.8 for I-ioflupane scintigraphy. The combined use of both scintigraphies was studied using the formula SBR×H/M ratio as a marker for the logistic regression model.. Sixteen (33.3%) patients had SBR of greater than 3.8: eight with PD; eight were controls. Five of eight patients had an H/M ratio of less than or equal to 2.2 (62.5%) and had PD. In the receiver-operating characteristic analysis, the SBR×H/M ratio cutoff was 12.5, with an area under the curve of 0.844 (95% confidence interval: 0.619-1). In an age-adjusted regression analysis in patients with SBR of greater than 3.8, the SBR×H/M ratio was associated significantly with an odds ratio of 0.69 (95% confidence interval: 0.48-0.98, P=0.041).. If SBR is greater than 3.8, the SBR×H/M ratio can help diagnose PD. The combined use of the two scintigraphies can improve the diagnosis of PD.

Topics: 3-Iodobenzylguanidine; Aged; Female; Humans; Logistic Models; Male; Middle Aged; Nortropanes; Parkinson Disease; Radionuclide Imaging; Sensitivity and Specificity

Depression frequently accompanies Parkinson's disease and often precedes the onset of motor symptoms. This study aimed to evaluate the impact of depression on motor compensation in patients with de novo Parkinson's disease. This retrospective cohort study analyzed data from 474 non-demented patients with de novo Parkinson's disease (mean age, 64.6±9.8 years; 242 men) who underwent both dopamine transporter PET scan and depression assessment using the Beck Depression Inventory at baseline. Patients were classified into tertiles by Beck Depression Inventory score. At baseline, high-tertile group (Beck Depression Inventory score ≥15, n = 157) showed more severe motor deficits and lower cognitive function than low-tertile group (Beck Depression Inventory score ≤7, n = 158, P = 0.034 and P = 0.008, respectively). Greater motor deficits in high-tertile group than low-tertile group remained significant after controlling for dopamine transporter binding in the posterior putamen, as well as other confounding variables. During follow-up of a median duration of 47 months, high-tertile group received higher levodopa-equivalent doses for symptom control than did low-tertile group after controlling for age, gender, and initial motor deficit severity. These results demonstrate that depression in de novo Parkinson's disease is associated with motor deficit severity at baseline and dose of PD medications during follow-up, suggesting that the presence of depression in de novo Parkinson's disease represents poor motor compensation.

Topics: Adult; Aged; Aged, 80 and over; Cognition; Cohort Studies; Depression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Levodopa; Male; Middle Aged; Motor Skills; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tropanes

Dopaminergic loss on. We aimed to develop a new visual rating scale for. Four experienced observers developed and tested a new scale consisting of two metrics, reflecting overall loss and heterogeneity of loss. 66 subjects were used during development including clinical diagnoses of Alzheimer's disease (n = 14), Parkinson's disease (n = 9), Parkinson's disease dementia (n = 9), dementia with Lewy bodies (n = 15) and normal controls (n = 19). The scale was then tested on an independent group of 46 subjects with autopsy confirmed diagnosis: Alzheimer's disease (n = 11), Parkinson's disease (n = 3), Parkinson's disease dementia (n = 15), dementia with Lewy bodies (n = 12), normal controls (n = 4) and Frontotemporal dementia (n = 1).. In the autopsy validation the sensitivity and specificity of the new scale for Lewy body disease was 97% and 100% respectively, compared with the standard scale which had the same sensitivity (97%), but lower specificity (80%). The new scale had excellent inter rater reliability (intra-class correlation coefficient 0.93).. A new robust and reliable rating scale is described that straightforwardly captures the visual appearance of

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Female; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Nortropanes; Parkinson Disease; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD).. The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients.. Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients.. The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated.. PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.

Topics: Adult; Alanine; alpha-Synuclein; Cognition Disorders; Cohort Studies; Corpus Striatum; Dopamine; Female; Functional Laterality; Humans; Male; Middle Aged; Mutation; Parkinson Disease; Threonine; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Aged; Brain; Dopamine; Female; Follow-Up Studies; Humans; Hydrocephalus, Normal Pressure; Magnetic Resonance Imaging; Mental Status Schedule; Neurologic Examination; Parkinson Disease; Positron-Emission Tomography; Tropanes; Ventriculoperitoneal Shunt

To compare diagnostic performance of [. A multicenter retrospective case-control study was conducted to evaluate whether the diagnostic performance of [. In total, 102 non-Caucasians (58 with PD and 44 with ET as a final clinical diagnosis) and 102 Caucasians (58 with PD, 43 with ET, and 1 with "other") were included in the intent-to-diagnose (ITD) population. There was no significant difference between Caucasians and non-Caucasians in the diagnostic performance of [. In this study, the diagnostic performance of [

Topics: Aged; Brain; Case-Control Studies; Essential Tremor; Female; Humans; Male; Middle Aged; Nortropanes; Observer Variation; Parkinson Disease; Racial Groups; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.. We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers.. CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β. CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Topics: Aged; alpha-Synuclein; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Electroencephalography; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Peptide Fragments; Psychiatric Status Rating Scales; Retrospective Studies; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

To examine whether combined use of. Patients with probable PD (n=120) who underwent both DAT-SPECT and MIBG myocardial scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of DAT-SPECT images and heart-to-mediastinum (H/M) ratio of MIBG images were used as quantitative measures. We classified patients into 4 groups based on SBR value and H/M ratio, or into two groups based on the striatal asymmetry index (SAI) of DAT-SPECT, and examined the clinical features of each group. We also investigated the characteristics of SWEDDs (scans without evidence of dopaminergic deficits) patients. Finally, we calculated the sensitivity and specificity of each method and the combined method.. SBR value was significantly correlated with both early and delayed H/M ratio values. Motor complications and hallucinations were observed at high frequency in the group with both lower SBR and H/M ratio, and hallucinations appeared in the group with larger SAI. SWEDDs were observed 8.3% of patients. The sensitivity and specificity of diagnosing PD were 91.7% and 15.0% by SBR of DAT-SPECT, 78.3% and 90.0% by H/M ratio of MIBG uptake, and 74.2% and 95.0% by the combined modalities, respectively.. Combined use of DAT-SPECT and MIBG myocardial scintigraphy increases the specificity of PD diagnosis, and is helpful for understanding the clinical features or predicting complications.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Parkinson Disease; Severity of Illness Index; Statistics as Topic; Tropanes

Parkinson's disease (PD) is among the most prevalent neurodegenerative conditions. While motor and non-motor aspects of this disease have been well characterized, no objective biomarker exists to support an accurate clinical diagnosis. However, newer imaging techniques, including [123I]-FP-CIT (DaTSCAN), have demonstrated utility in differentiating between PD and non-neurodegenerative tremor disorders.. DaTSCAN has been primarily investigated in situations where diagnostic confusion exists, and in these instances has been shown to significantly impact clinical management. The goal of this pilot study was to evaluate the impact of DaTSCAN on the clinical management of patients with early probable PD, where no diagnostic uncertainty exists.. This was a prospective, 54-week, comparative pilot study, in which twenty subjects with de novo PD were randomly assigned to DaTSCAN either immediately upon diagnosis (and again at 6 and 12 months) or delayed to 6 months (and again at 12 months). The primary outcome measure was the frequency of deviation from the initial treatment plan from baseline to 54 weeks between the two groups. Secondary outcomes included motor and non-motor assessments.. There was no significant difference in the number of treatment changes over the course of the study between the two groups: initial imaging group = 4.2 (SD:2.74) vs. delayed imaging group = 2.3 (SD:2.0, p = 0.11). In addition, there were no group differences in medication requirements, motor performance, or patient expectations of disease.. In patients with early, probable PD, DaTSCAN contributes no additional impact on clinical management or functional outcomes when added to the diagnostic algorithm.

Topics: Aged; Biomarkers; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Pilot Projects; Prospective Studies; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tropanes

Topics: Dystonic Disorders; Female; Functional Laterality; GTP Cyclohydrolase; Humans; Levodopa; Magnetic Resonance Imaging; Mutation; Parkinson Disease; Positron-Emission Tomography; Tropanes; Young Adult

Molecular imaging of nigrostriatal dopamine transporters (DAT) and sympathetic cardiac innervation with single-photon emission computed tomography (SPECT) are useful tools for differentiating idiopathic Parkinson disease (PD) from other degenerative parkinsonian syndromes (non-PD). Nevertheless, these modalities are often insufficient for achieving a definite diagnosis. The aims of this study were to evaluate the diagnostic accuracy of the combination of these tools.. The SPECT radiotracers [I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) and meta-[I]-iodobenzylguanidine (MIBG) were used to research presynaptic dopaminergic projections (DAT SPECT) and myocardial adrenergic innervation (MIBG scintigraphy), respectively. PD patients (n=15; age: 61.5±13.6 years) and non-PD patients (n=19; age: 62.6±14.2 years) who underwent both tests were enrolled in this study. Receiver-operating characteristic analyses were used to set the cutoff values of the specific binding ratio in DAT SPECT and the heart to mediastinum ratio in delayed scan in MIBG scintigraphy for differentiating PD from non-PD. We calculated the sensitivity, specificity, and test accuracy of the individual methods and also the combination of these two modalities.. When DAT SPECT and MIBG scintigraphy were used individually, they showed mild accuracy in differentiating PD from non-PD (DAT, 67.6%; MIBG, 67.6%). The combination of the two approaches using cutoff values of less than 3.24 for the specific binding ratio and less than 2.745 for the delayed heart to mediastinum ratio enabled more accurate differentiation between PD and non-PD. The accuracy of these indices in distinguishing PD from non-PD was 79.4%.. These results suggested that the combination of DAT SPECT and MIBG scintigraphy may improve the diagnostic accuracy in differentiating PD from non-PD.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Parkinson Disease; Parkinsonian Disorders; ROC Curve; Tomography, Emission-Computed, Single-Photon; Tropanes

Detecting individuals at risk for Parkinson disease (PD) during the prodromal phase could clarify disease mechanisms and allow for treatment earlier in the disease process to possibly slow or prevent the onset of motor PD.. To determine if the combination of smell identification testing followed by dopamine transporter (DAT) imaging can accurately and efficiently identify individuals from the general population at risk for conversion to a clinical diagnosis of PD.. Participants were identified from the community by olfactory testing assessed longitudinally with DAT imaging 2 and 4 years after baseline and by annual clinical follow-up to determine whether they had clinical evidence to establish a PD diagnosis. Participants were contacted by mail and completed olfactory testing at home. Longitudinal follow-up of clinical measures and DAT imaging occurred at specialty centers. There were 203 hyposmic and 100 normosmic participants. A total of 185 hyposmic and 95 normosmic individuals had at least 1 follow-up visit, and 152 hyposmic participants (82.2%) were either observed for 4 years or converted to PD during follow-up.. Percentage of individuals with hyposmia and a DAT deficit that converted to PD and the change in PD clinical scale scores (Unified Parkinson's Disease Rating Scale) and DAT imaging during 4-year follow-up.. Of 280 total participants, 140 (50.0%) were male, and the mean (SD) age of the cohort was 63 (8.7) years. Among 21 participants with hyposmia and a DAT deficit (65% or less of age-expected lowest putamen binding ratio) at baseline, 14 (67%) converted to PD at 4 years compared with 2 of 22 participants (9%) with a DAT in an indeterminate range (greater than 65%-80%) and 3 of 109 participants (2.8%) with no DAT deficit (greater than 80%) at baseline. Individuals with a baseline DAT deficit experienced a 4-year decline in DAT binding of 20.23% (SD, 15.04%) compared with 3.68% (SD, 18.36%) and 5.45% (SD, 13.58%) for participants with an indeterminate and no DAT deficit, respectively (P = .002). The relative risk of conversion to a diagnosis of PD in hyposmic individuals with a DAT deficit was 17.47 (95% CI, 7.02-43.45) compared with individuals with either indeterminate or no DAT deficit.. The combination of hyposmia and DAT deficit was highly predictive of conversion to PD within 4 years of clinical follow-up. Individuals with hyposmia and a DAT deficit had a 5% reduction in DAT binding annually, similar to early PD. These results provide a framework for planning disease prevention studies in PD.

Topics: Aged; Chi-Square Distribution; Cohort Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Olfaction Disorders; Parkinson Disease; Prodromal Symptoms; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

To produce coordinated manual actions within specific space and time, their relationship must be properly dealt with in a sensorimotor system. This study examined how such a coordination system might be impaired in normal aging and in Parkinson's disease (PD). Using a tablet device, young participants, elderly participants, and patients with PD were tested for concurrent production of distance and duration as well as single production of distance or duration alone. Results were analyzed in relation to deficiency of presynaptic dopamine transporter (DaT) in the striatum. We observed different patterns of impairment between normal aging and PD. Elderly participants exhibited duration overproduction when they had to produce distance and duration concurrently, but were normal in single production of either distance or duration. In contrast, PD patients exhibited normal distance production and marked underproduction of duration when either distance or duration was produced alone, but both duration and distance were underproduced when they were concurrently produced. These findings suggest that aging yields impaired performances in both elderly people and PD patients, but that temporal underproduction in PD patients entrains spatial production as if the distance to be produced were made consistent with their duration underproduction. We also observed that striatal DaT deficit was correlated with the extent of duration underproduction in PD patients. The deficit may be associated with the severe time compression and the entrainment during spatiotemporal production in PD patients.

Topics: Age Factors; Aged; Analysis of Variance; Cognition Disorders; Corpus Striatum; Feedback; Female; Functional Laterality; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Perceptual Disorders; Spatial Navigation; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography-based network analysis was performed to assess structural connectivity in cerebello-thalamo-basal ganglia-cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single-photon emission computed tomography (DAT-SPECT) with

Topics: Aged; Brain Mapping; Cohort Studies; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Nortropanes; Parkinson Disease; Phenotype; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tremor

In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin-along with its related serum markers- and striatal presynaptic dopaminergic denervation measured with I-FP-CIT SPECT.. We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism). Serum ceruloplasmin and related serum markers, such as copper, iron, total iron-binding capacity, and ferritin, were measured. Specific binding ratios of the striatum, caudate nucleus, putamen, and posterior putamen were obtained by I-FP-CIT SPECT.. There was no difference in the serum markers, except for ceruloplasmin, between the 2 groups. Ceruloplasmin level was significantly lower in PD patients with longer symptom duration (>2 years) than in the disease control group (21.4 ± 3.4 vs 24.0 ± 3.8, P = 0.03). Serum ceruloplasmin had a significant correlation with specific binding ratios of the striatum, caudate nucleus, and putamen in a subgroup with longer symptom duration (P = 0.01, P = 0.02, P = 0.02, respectively, for the subgroup with symptom duration >1 year, and P < 0.01, P < 0.01, P = 0.04, respectively, for the subgroup with symptom duration >2 years).. Decrease in serum ceruloplasmin had a positive correlation with a decrease in dopamine transporter density in PD patients with symptom duration of more than 1 year.

Topics: Aged; Ceruloplasmin; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) patients show cognitive deficits that are relevant in terms of prognosis and quality of life. Degeneration of striatal dopaminergic afferents proceeds from dorsal/caudal to anterior/ventral and is discussed to account for some of these symptoms. Treatment with dopamine (DA) has differential effects on cognitive dysfunctions, improving some and worsening others. We hypothesized that cognitive performance during the dopaminergic OFF state correlates with DAT availability in the associative striatum. 16 PD patients underwent motor and cognitive examination ON and OFF DA. Global cognition was measured using the Montréal Cognitive Assessment (MoCA) test and executive functioning using a Stroop test. Nigrostriatal dopaminergic innervation was characterized with [

Topics: Adult; Aged; Brain Mapping; Cognition; Cognitive Dysfunction; Cohort Studies; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Executive Function; Female; Humans; Male; Middle Aged; Nerve Degeneration; Neuropsychological Tests; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate whether dopamine transporter (DAT) binding, as measured with single photon emission computed tomography (SPECT), can be used to predict mortality in patients with Parkinson's disease (PD).. A total of 162 patients with PD and abnormal [I-123]FP-CIT SPECT were clinically followed for a median of 5.8 years. A multivariate Cox regression model was used to investigate survival with the independent predictors of age, gender, severity of motor impairment, levodopa-equivalent daily dose of medication, presence of cognitive defects, and putaminal specific binding ratio (SBR) of [I-123]FP-CIT. In addition, associations between striatal and extrastriatal SBRs and survival were investigated using voxel-based analyses.. The overall mortality was 25.9%, and the Kaplan-Meier estimate for mortality was 36%. Older age (P < 0.001), presence of cognitive defects (P = 0.001), and more severe motor symptom severity (P = 0.002) were significantly associated with increased mortality. No associations were found between putaminal DAT binding and survival (P = 0.99). There were no significant differences in SBRs in any striatal or extrastriatal region between survivors and non-survivors, and no associations were found between SBRs and scan-to-death intervals among non-survivors.. Unlike the severity of motor and cognitive symptoms, the level of striatal dopaminergic defect in DAT SPECT does not predict mortality in PD. Although presynaptic dopaminergic functional imaging may have value as a diagnostic tool, the clinical symptom-based characteristics are superior for predicting lifespan.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Motor Activity; Parkinson Disease; Protein Binding; Retrospective Studies; Survival; Tomography, Emission-Computed, Single-Photon; Tropanes

To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic. Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (. Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the

Topics: Age Factors; Brain Mapping; Corpus Striatum; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Family; Female; Heterozygote; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Longitudinal Studies; Male; Middle Aged; Mutation; Nortropanes; Parkinson Disease; Prodromal Symptoms; Prospective Studies; Radiopharmaceuticals; Severity of Illness Index; Smell; Tomography, Emission-Computed, Single-Photon

Scans without evidence of dopaminergic deficits (SWEDDs) in dopamine transporter single-photon emission computed tomography (DAT-SPECT) are found in 3.6-19.6% of patients with clinically suspected Parkinson's disease (PD). We investigated whether combined use of. 145 patients with clinically suspected PD underwent both DAT-SPECT and MIBG myocardial scintigraphy. Striatal binding ratio (SBR) of DAT-SPECT and heart-to-mediastinal (H/M) ratio and washout rate (WR) of MIBG myocardial scintigraphy were calculated.. Among 18 SWEDDs patients (12.4%), 11 were finally diagnosed with PD based on follow-up for at least two years after the DAT-SPECT and MIGB myocardial scintigraphy scans. Among the latter group, 8 patients showed an H/M ratio of less than 2.2, and 9 showed WR above 30%.. Our results indicate that the combination of low H/M ratio and high WR of MIBG myocardial scintigraphy of SWEDDs patients may be helpful for detection of PD patients.

Topics: 3-Iodobenzylguanidine; Adult; Aftercare; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

The dominant approach to neuroimaging data analysis employs the voxel as the unit of computation. While convenient, voxels lack biological meaning and their size is arbitrarily determined by the resolution of the image. Here, we propose a multivariate spatial model in which neuroimaging data are characterised as a linearly weighted combination of multiscale basis functions which map onto underlying brain nuclei or networks or nuclei. In this model, the elementary building blocks are derived to reflect the functional anatomy of the brain during the resting state. This model is estimated using a Bayesian framework which accurately quantifies uncertainty and automatically finds the most accurate and parsimonious combination of basis functions describing the data. We demonstrate the utility of this framework by predicting quantitative SPECT images of striatal dopamine function and we compare a variety of basis sets including generic isotropic functions, anatomical representations of the striatum derived from structural MRI, and two different soft functional parcellations of the striatum derived from resting-state fMRI (rfMRI). We found that a combination of ∼50 multiscale functional basis functions accurately represented the striatal dopamine activity, and that functional basis functions derived from an advanced parcellation technique known as Instantaneous Connectivity Parcellation (ICP) provided the most parsimonious models of dopamine function. Importantly, functional basis functions derived from resting fMRI were more accurate than both structural and generic basis sets in representing dopamine function in the striatum for a fixed model order. We demonstrate the translational validity of our framework by constructing classification models for discriminating parkinsonian disorders and their subtypes. Here, we show that ICP approach is the only basis set that performs well across all comparisons and performs better overall than the classical voxel-based approach. This spatial model constitutes an elegant alternative to voxel-based approaches in neuroimaging studies; not only are their atoms biologically informed, they are also adaptive to high resolutions, represent high dimensions efficiently, and capture long-range spatial dependencies, which are important and challenging objectives for neuroimaging data.

Topics: Aged; Bayes Theorem; Corpus Striatum; Dopamine; Female; Functional Neuroimaging; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Models, Theoretical; Neuroimaging; Parkinson Disease; Spatial Analysis; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson's disease (PD) using double brain imaging, 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) PET and 123I-FP-CIT SPECT.. Nine PD patients were studied with brain 62Cu-ATSM PET for oxidative stress and 123I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic 62Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, 62Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of 123I-FP-CIT (SUVR/SBR).. 62Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson's Disease Rating Scale (UPDRS) scores or 123I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and 123I-FP-CIT SBR.. Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. 62Cu-ATSM PET with 123I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.

Topics: Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Nerve Degeneration; Neuroimaging; Oxidative Stress; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

Topics: Aged; Algorithms; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Machine Learning; Male; Middle Aged; Neural Networks, Computer; Neuroimaging; Parkinson Disease; Radionuclide Imaging; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Adrenal Insufficiency; Adrenoleukodystrophy; Adult; ATP Binding Cassette Transporter, Subfamily D, Member 1; Delayed Diagnosis; Dopamine Plasma Membrane Transport Proteins; Dyslipidemias; Female; Genetic Carrier Screening; Genetic Counseling; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Point Mutation; Positron-Emission Tomography; Young Adult

This study analyzed data from dopamine transporter (DAT) positron emission tomographic scans of 282 male patients with de novo Parkinson disease to investigate whether smoking impacts striatal dopamine neuronal degeneration. Mean DAT activity in the posterior (p = 0.016) and ventral putamen (p = 0.028) was higher in 44 current smokers in comparison to 105 ex-smokers and 133 never-smokers. The severity of baseline motor deficits and the longitudinal increases in levodopa-equivalent doses during follow-up were similar among the 3 groups. These results suggest that current smoking, but not past smoking, protects dopamine neuronal degeneration in the sensorimotor striatum with no additional clinical benefits. Ann Neurol 2017;82:850-854.

Topics: Aged; Case-Control Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Functional Neuroimaging; Humans; Male; Middle Aged; Nerve Degeneration; Parkinson Disease; Positron-Emission Tomography; Protective Factors; Smoking; Tropanes

Parkinson's disease (PD) is caused by a selective degeneration of dopamine neurons. The relationship between dopamine transporter (DAT) density and gray matter volume has been unclear. Here we investigated the voxelwise correlation between gray matter volume and DAT binding measured by. Thirty-one male patients with PD were examined with MRI and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships between the regional gray matter volume and the SBR in the striatum.. There were significant positive correlations between the SBR and the gray matter volume in the right pulvinar and posterior middle temporal gyrus and a trend level in the left pulvinar, all of which are associated with the second visual pathway.. The nigrostriatal dopaminergic degeneration might affect the secondary visual pathway, leading to visual dysfunctions in PD.

Topics: Adult; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organ Size; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level.. Step-wise logistic regression selected the posterior qEEG mean frequency and. Resting EEG and

Topics: Aged; Cognition Disorders; Electroencephalography; Female; Humans; Logistic Models; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Predictive Value of Tests; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

The purpose of this study was to assess the influence of different reconstruction factors in N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-I-123 iodophenyl)nortropane (I-123 FP-CIT) single-photon emission computed tomography (SPECT) images for the diagnosis of dopaminergic system neurodegeneration (DSND).Seventy-three patients (38 females, 35 males) suspected of DSND were included in this study. The patients were divided into 3 groups on the basis of their final clinical diagnoses; patients with Parkinson disease (group 1, n = 36), patients with other DSND (group 2, n = 19), patients without DSND (group 3, n = 18). FP-CIT accumulation in the striata was evaluated visually and semiquantitatively. SPECT images were classified visually as normal or abnormal based on the previous report. For semiquantitative analysis, we used DaTView software (Aze Corporation), and specific binding ratios (SBR) and asymmetry indices (AI) were calculated. Visual and semiquantitative evaluations for different reconstruction factors were compared among the 3 groups.In the visual evaluation, there were no differences among DSND diagnostic capabilities of attenuation and scatter correction by computed tomography attenuation correction scatter correction, computed tomography attenuation correction, Chang attenuation correction, and non-attenuation and -scatter correction. In the semiquantitative evaluation, receiver operating characteristic analysis of SBR and AI for clinical DSND diagnostic ability (group 1+2 vs 3) showed no significant difference among the reconstruction factors by multiple comparisons.Although the values of SBR and AI were changed and image quality could be improved when attenuation correction and/or scatter correction were applied, the clinical impact of these reconstruction factors for the diagnosis of DSND was negligible.

Topics: Aged; Aged, 80 and over; Dopamine; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neurodegenerative Diseases; Parkinson Disease; Radiopharmaceuticals; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropanes

The demonstration of presynaptic dopaminergic deficiency on [. Our primary aim was to assess the correlations between dopaminergic deficiency on baseline [. 42 PD patients with abnormal baseline [. The degree of dopaminergic deficiency on baseline [

Topics: Aged; Disease Progression; Female; Humans; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.. The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.. CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.

Topics: Aged; Aged, 80 and over; Algorithms; Case-Control Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Reference Standards; Single Photon Emission Computed Tomography Computed Tomography; Tropanes

Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset.. The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset.. A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance.. EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044).. Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.

Topics: Age of Onset; Aged; Case-Control Studies; Cerebral Cortex; Cognition Disorders; Dementia; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Statistics, Nonparametric; Tropanes

Life-long experiences of cognitive activity could enhance cognitive reserve, which may lead individuals to show less cognitive deficits in Alzheimer's disease, despite similar pathological changes. We performed this study to test whether premorbid physical activity may enhance motor reserve in Parkinson's disease (PD) (i.e., less motor deficits despite similar degrees of dopamine depletion).. We assessed engagement in premorbid leisure-time exercise among 102 drug naive PD patients who had been initially diagnosed at our hospital by dopamine transporter scanning. Patients were classified into tertile groups based on the frequency, duration, and intensity of the exercises in which they participated.. Among patients with mild to moderate reductions in striatal dopaminergic activity (above the median dopaminergic activity), the exercise group of the highest tertile showed significantly lower motor scores (i.e., fewer motor deficits, 15.53 ± 6.25), despite similar degrees of dopamine reduction, compared to the combined group of the middle and the lowest tertiles (21.57 ± 8.34, p = 0.01). Nonetheless, the highest tertile group showed a more rapid decline in motor function related to reductions in striatal dopaminergic activity than the other two groups (p = 0.002 with the middle tertile group and p = 0.001 with the lowest tertile group).. These results suggest that engagement in premorbid exercise acts as a proxy for an active reserve in the motor domain (i.e., motor reserve) in patients with PD.

Topics: Adult; Aged; Aged, 80 and over; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Exercise; Female; Humans; Male; Mental Status Schedule; Middle Aged; Motor Activity; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Retrospective Studies; Severity of Illness Index; Tropanes

Topics: Aged; Biomarkers; Brain; Corpus Striatum; Diagnosis, Differential; Humans; Male; Parkinson Disease; Protein Binding; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Regional cerebral perfusion is coupled to metabolism in general. Early perfusion dominant imaging using F-FP-CIT PET (pCIT) may provide complementary information to delayed dopamine transporter dominant images. We investigated the ability of pCIT to differentiate atypical Parkinson disorder from Parkinson disease (PD) compared to FDG and the image quality for optimizing the acquisition time.. Sixty-seven subjects [PD, 23 subjects; multiple system atrophy-cerebellar type (MSA-C), 27 subjects; MSA-Parkinson type (MSA-P), 12 subjects; and progressive supranuclear palsy (PSP), 5 subjects] underwent F-FP-CIT and FDG PET. Using dynamic PET data acquired during the first 10 minutes after F-FP-CIT administration, we generated potential perfusion images of 0 to 5 (pCIT-5m), 0 to 7 (pCIT-7m), and 0 to 10 (pCIT-10m) minutes. We compared regional uptake between groups in pCIT and FDG images and image quality among pCIT images using visual, quantitative, or statistical parametric mapping analyses.. Regional cerebral uptake of pCITs correlated well to that of the FDG images (R > 0.5, all). Multiple system atrophy-cerebellar type and MSA-P groups show different regional uptake patterns compared with PD group on pCITs in quantitative and statistical parametric mapping analyses, analogous to FDG images, but not in the PSP group. In visual analysis, concordance rates between each pCIT and FDG image were high (92.3%-96.0%, regional; 86.2%-93.1%, diagnostic), and there was no significant difference among pCITs. However, pCIT-10m discriminated PSP better than others and showed higher signal-to-noise ratio (P = 0.001).. F-FP-CIT PETs with the first 10 minutes could be useful for the differential diagnosis of atypical Parkinson disorder by providing complementary FDG-like information to the dopamine transporter binding on late-phase FP-CIT images.

Topics: Aged; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tropanes

To evaluate a potential multisystem involvement of neurodegeneration in Asidan, in addition to cerebellar ataxia and signs of motor neuron disease.. Both the PD and PSP groups served as positive controls for DAT decline. The PD and PSP groups served as a positive and negative control, respectively, of MIBG decline in the early phase H/M ratio. Of the Asidan patients, 60.0% showed DAT decline without evident parkinsonian features and 6.7% showed impaired MIBG in only the delayed phase H/M ratio. Combined with a normal range of the early phase H/M ratio, this phenotype was newly named Declined DAT Without Evident Parkinsonism (DWEP).. The results of present study including DWEP suggest a wider spectrum of neurodegeneration for extrapyramidal and autonomic systems in Asidan patients than expected, involving cerebellar, motor system and cognitive functioning.

Topics: 3-Iodobenzylguanidine; Aged; Brain; Family; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Perfusion Imaging; Parkinson Disease; Pedigree; Radiopharmaceuticals; Spinocerebellar Degenerations; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = -0.377, p = 0.048), with olfactory function (ρ = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.

Topics: Aged; alpha-Synuclein; Biomarkers; Biopsy; Brain; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Fluorescent Antibody Technique; Humans; Leg; Male; Middle Aged; Parkinson Disease; Phosphorylation; Prodromal Symptoms; Prospective Studies; Radiopharmaceuticals; REM Sleep Behavior Disorder; Skin; Smell; Tomography, Emission-Computed, Single-Photon; Tropanes

[. One hundred forty-three subjects [84 with Parkinson's disease (PD) and 59 control individuals (CG)] underwent DATSCAN® imaging. The [. As compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [. The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in [

Topics: Aged; Case-Control Studies; Demography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: alpha-Synuclein; Female; Humans; Lewy Body Disease; Locus Coeruleus; Middle Aged; Mutation; Parkinson Disease; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

A comprehensive analysis of the Parkinson's Progression Markers Initiative (PPMI) Dopamine Transporter Single Photon Emission Computed Tomography (DaTscan) images is carried out using a voxel-based logistic lasso model. The model reveals that sub-regional voxels in the caudate, the putamen, as well as in the globus pallidus are informative for classifying images into control and PD classes. Further, a new technique called logistic component analysis is developed. This technique reveals that intra-population differences in dopamine transporter concentration and imperfect normalization are significant factors influencing logistic analysis. The interactions with handedness, sex, and age are also evaluated.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Mapping; Caudate Nucleus; Disease Progression; Female; Globus Pallidus; Humans; Imaging, Three-Dimensional; Machine Learning; Male; Middle Aged; Parkinson Disease; Principal Component Analysis; Putamen; Signal Processing, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: alpha-Synuclein; Fluorodeoxyglucose F18; Humans; Kidney Diseases; Parkinson Disease; Tropanes

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD).. This retrospective study included 970 consecutive patients undergoing (123)I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.. Increasing disease stage was associated with an exponential decrease in (123)I-ioflupane uptake (R(2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in (123)I-ioflupane uptake (p < 0.0001; R(2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001).. We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 (123)I-ioflupane SPECT scans can be used for clinical and research applications.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Corpus Striatum; Disease Progression; Dopamine; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Nortropanes; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

The aim of this study was to evaluate whether striatal dopamine transporter (DAT) loss as measured by (18)F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane ([(18)F]FP-CIT) PET differs according to the metabolic subtype of multiple system atrophy (MSA) as assessed by [(18)F]FDG PET.. This retrospective study included 50 patients with clinically diagnosed MSA who underwent [(18)F]FP-CIT and [(18)F]FDG brain PET scans. The PET images were analysed using 12 striatal subregional volume-of-interest templates (bilateral ventral striatum, anterior caudate, posterior caudate, anterior putamen, posterior putamen, and ventral putamen). The patients were classified into three metabolic subtypes according to the [(18)F]FDG PET findings: MSA-Pm (striatal hypometabolism only), MSA-mixedm (both striatal and cerebellar hypometabolism), and MSA-Cm (cerebellar hypometabolism only). The subregional glucose metabolic ratio (MRgluc), subregional DAT binding ratio (BRDAT), and intersubregional ratio (ISRDAT; defined as the BRDAT ratio of one striatal subregion to that of another striatal subregion) were compared according to metabolic subtype.. Of the 50 patients, 13 presented with MSA-Pm, 16 presented with MSA-mixedm, and 21 presented with MSA-Cm. The BRDAT of all striatal subregions in the MSA-Pm and MSA-mixedm groups were significantly lower than those in the MSA-Cm group. The posterior putamen/anterior putamen ISRDAT and anterior putamen/ventral striatum ISRDAT in the MSA-Pm and MSA-mixedm groups were significantly lower than those in the MSA-Cm group.. Patients with MSA-Pm and MSA-mixedm showed more severe DAT loss in the striatum than patients with MSA-Cm. Patients with MSA-Cm had more diffuse DAT loss than patients with MSA-Pm and MSA-mixedm.

Topics: Adult; Aged; Brain; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Female; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tropanes

To assess whether cigarette smoking interferes with dopaminergic transmission in current- and never-smoking patients with Parkinson's disease.. Striatal [123I]FP-CIT single photon emission computed tomography was performed in 67 patients with Parkinson's disease (35 women and 32 men aging 60.8 ± 10.1 years and staging 1.76 ± 0.5 on the Hoehn and Yahr scale). At study time, there were 13 current-smokers and 54 never-smokers.. Current-smokers showed a significantly lower putamen/occipital [123I]FP-CIT ratio and a non-significant trend to a lower caudate/occipital [123I]FP-CIT ratio uptake. Current-smokers were also characterized by a lower off UPDRS-III motor score. A logistic regression analysis adjusted for age, sex, disease duration, Hoehn and Yahr staging, and medication indicated a significant lower [123I]FP-CIT uptake not only in the putamen (odds ratio, 0.1; 95% confidence interval, 0.01 to 0.65; P = 0.02) but also in the caudate (odds ratio, 0.2; 95% confidence interval, 0.04 to 0.71; P = 0.015) as well as a lower UPDRS-III motor score (odds ratio, 0.9; 95% confidence interval, 0.81 to 0.99; P = 0.04) in current-smokers.. The lower [123I]FP-CIT uptake together with the lower UPDRS-III motor score observed in our current-smokers patients with Parkinson's disease (even taking into account variables that are probably expression of dopaminergic neuron decline and treatment) would support an effect of smoking on dopaminergic synaptic mechanisms.

Topics: Aged; Corpus Striatum; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Movement; Occipital Lobe; Parkinson Disease; Putamen; Radiopharmaceuticals; Smoking; Tomography, Emission-Computed, Single-Photon; Tropanes

Inaccuracy in MR image-based attenuation correction (MR-AC) leads to errors in quantification and the misinterpretation of lesions in brain PET/MRI studies. To resolve this problem, we proposed an improved ultrashort echo time MR-AC method that was based on a multiphase level-set algorithm with main magnetic field (B0) inhomogeneity correction. We also assessed the feasibility of this level-set-based MR-AC method (MR-AC(level)), compared with CT-AC and MR-AC provided by the manufacturer of the PET/MRI scanner (MR-AC(mMR)).. Ten healthy volunteers and 20 Parkinson disease patients underwent(18)F-FDG and(18)F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET scans, respectively, using both PET/MRI and PET/CT scanners. The level-set-based segmentation algorithm automatically delimited air, bone, and soft tissue from the ultrashort echo time MR images. For the comparison, MR-AC maps were coregistered to reference CT. PET sinogram data obtained from PET/CT studies were then reconstructed using the CT-AC, MR-AC(mMR), and MR-AC(level) maps. The accuracies of SUV, SUVr (SUV and its ratio to the cerebellum), and specific-to-nonspecific binding ratios obtained using MR-AC(level) and MR-AC(mMR) were compared with CT-AC using region-of-interest- and voxel-based analyses.. There was remarkable improvement in the segmentation of air cavities and bones and the quantitative accuracy of PET measurement using the level set. Although the striatal and cerebellar activities in (18)F-FP-CIT PET and frontal activity in (18)F-FDG PET were significantly underestimated by the MR-AC(mMR), the MR-AC(level) provided PET images almost equivalent to the CT-AC images. PET quantification error was reduced by a factor of 3 using MR-AC(level) (SUV error < 10% in MR-AC(level) and < 30% in MR-AC(mMR) [version VB18P], and < 5% in MR-AC(level) and < 15% in MR-AC(mMR) [VB20P]).. The results of this study indicate that our new multiphase level-set-based MR-AC method improves the quantitative accuracy of brain PET in PET/MRI studies.

Topics: Aged; Algorithms; Bone and Bones; Electromagnetic Fields; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

(123)I-ioflupane SPECT (DaTscan) is an examination that detects presynaptic dopamine neuronal dysfunction, and has been used as a diagnostic tool to identify degenerative parkinsonism. Additionally, myocardial (123)I-metaiodobenzyl guanidine (MIBG) scintigraphy measures the concentration of cardiac sympathetic nerve fibers and is used to diagnose Parkinson's disease (PD). These exams are used as adjuncts in the diagnosis of parkinsonism, however, the relationship of these two examinations are not well-known. We investigated the relationship of these two scanning results specifically for determining the use of deep brain stimulation therapy (DBS). Subjects were Japanese patients with suspected striatonigral degeneration, including PD; DaTscans and myocardial MIBG scintigraphy were performed. The mean values of the left-right specific binding ratios (SBRs) from the DaTscan, and the early/delayed heart-to-mediastinum ratios (HMRs) from the MIBG scintigraphy were calculated. Using simple linear regression analysis, we compared the SBR and early/delayed HMR values. Twenty-four patients were enrolled in this study. Twenty-one patients were positive via the DaTscan, and the MIBG scintigraphy results showed 14 patients were positive. SBR and both early and delayed HMR were positively correlated in cases of PD, but negative in non-PD cases. A mean SBR value less than 3.0 and a delayed HMR value less than 1.7 indicated a Hoehn-Yahr stage 3 or 4 for PD, which is commonly regarded as a level appropriate for initiating DBS therapy. Our results indicate that performing both DaTscan and MIBG scintigraphy is useful for the evaluation of surgical intervention in PD.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Deep Brain Stimulation; Female; Heart; Humans; Iodine Radioisotopes; Male; Middle Aged; Myocardium; Nortropanes; Parkinson Disease; Radionuclide Imaging; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent (18) F-FP-CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by (18) F-FP-CIT. Voxel-based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel-by-voxel correlation between BR maps and GM density maps was done to evaluate region-specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel-by-voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710-1721, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adult; Aged; Brain Mapping; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration; Parkinson Disease; Positron-Emission Tomography; Prospective Studies; Tropanes

In Alzheimer's disease, higher educational attainment is associated with fewer cognitive deficits despite similar pathological lesions. In animal models of Parkinson's disease (PD), enhanced levels of cognitive and physical stimulation can reduce motor deficits due to dopaminergic neuronal loss. Therefore, in this study, we tested whether higher educational attainment has a beneficial influence on PD motor symptoms.. We included data from 182 patients with de novo PD without dementia, who underwent dopamine transporter (DAT) scans for an initial diagnostic work-up. Patients were divided into 2 groups according to their educational attainment; high education (HE-PD; ≥12years of education) and low education (LE-PD; <12years of education).. The HE-PD group exhibited significantly higher mini-mental state exam scores, fewer motor deficits, and lower DAT binding to the posterior putamen than the LE-PD group, despite a similar duration of PD symptoms. A general linear model revealed that this difference in motor deficits remained statistically significant after controlling for potential confounding factors (p=0.032).. These results suggest that higher educational attainment can lead to reduced motor deficits in PD despite greater reductions in dopamine levels.

Topics: Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Educational Status; Female; Humans; Male; Mental Status Schedule; Middle Aged; Motor Activity; Parkinson Disease; Positron-Emission Tomography; Retrospective Studies; Tropanes

The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after median disease duration of 4.7 years (0.5-12.4 years). (18)F-AV-1451 positron emission tomography may be the first radiotracer to reflect the loss of pigmented neurons in the substantia nigra of parkinsonian patients. The magnitude of the nigral signal loss was smaller than the decrease in striatal dopamine transporter signal measured by dopamine transporter single photon emission computed tomography. These findings suggest a more severe loss of striatal nerve terminal function compared with neuronal c

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Female; Fluorine Radioisotopes; Humans; Male; Melanins; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Substantia Nigra; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Metaiodobenzylguanidine (MIBG) myocardial scintigraphy is widely accepted as a beneficial tool for differentiating Parkinson's disease (PD) from other Parkinson-related disorders (PRD). In Japan, dopamine transporter (DAT) imaging, which can evaluate presynaptic degeneration of dopamine neurons, has been applied in clinics since 2014. The present study investigated the utility of [(123)I]-Ioflupane single photon emission computed tomography (SPECT) combined with MIBG myocardial scintigraphy for the diagnosis of PD. We performed [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy in 63 PD patients, 8 PRD patients and 1 essential tremor patient, and obtained the specific binding ratio (SBR [cut-off: 4.5]) and the heart-to-mediastinum ratio (H/M [cut-off: 2.2]). In 70% of the PD patients, both parameters were significantly reduced. In 22% of the PD patients, the SBR was smaller than 4.5 with normal H/M, and H/M was less than 2.2 with normal SBR in 5% of all subjects. Either the SBR or H/M was significantly reduced in 97% of the study population. The SBR showed low disease specificity to PD (11%), and the SBR and H/M negatively correlated with disease duration. These findings indicate that [(123)I]-Ioflupane SPECT combined with MIBG myocardial scintigraphy can improve the detection rate of PD. However, careful interpretation of these results is required because [(123)I]-Ioflupane SPECT poorly differentiates PD from PRD. Progression of PD may reflect the gradual reduction of isotope accumulation, hence, both [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy should be tested repeatedly even in clinically suspected PD cases showing negative results.

Topics: 3-Iodobenzylguanidine; Aged; Diagnosis, Differential; Disease Progression; Female; Heart; Humans; Iodine Radioisotopes; Male; Middle Aged; Myocardial Perfusion Imaging; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Dopamine transporter single-photon emission computed tomography imaging utilizing iodine-123 ioflupane is accurate for differentiation of Parkinson disease from essential tremor. This study evaluates how reimbursement for I-123 ioflupane imaging changed between 2011 (year of FDA approval) and 2014 (year after loss of pass-through status for hospital-based outpatient imaging from CMS).. I-123 ioflupane reimbursement data for our institution's hospital-based imaging were compared between two periods: (1) July 2011 to October 2012, and (2) 2014. For each time period separately and in combination, averages and ranges of reimbursement for private insurance and CMS were analyzed and compared. A model to ensure recouping of radiopharmaceutical costs was developed.. Review yielded 247 studies from July 2011 to October 2012 and 94 studies from 2014. Average reimbursement per study fell from $2,469 (US dollars) in 2011 to 2012 to $1,657 in 2014. CMS reduced average reimbursement by $1,148 in 2014 because of loss of radiopharmaceutical pass-through status. Average reimbursements from CMS versus private payors markedly differed in 2011 to 2012 at $2,266 versus $2,861, respectively, and in 2014 at $1,118 versus $3,470, respectively. Between 2011 to 2012 and 2014, the CMS percentage increased from 54% to 78%. Assuming that I-123 ioflupane cost $2,000, our model based on 2014 data predicts a practice with greater than 60% CMS patients would no longer recover radiopharmaceutical costs.. Reimbursement levels, payor mix, scanner location, and radiopharmaceutical costs are all critical, variable factors for modeling the financial viability of I-123 ioflupane imaging and, by extrapolation, future radiopharmaceuticals.

Topics: Arizona; Cost-Benefit Analysis; Dopamine Plasma Membrane Transport Proteins; Health Care Costs; Health Services Accessibility; Insurance, Health, Reimbursement; Medicare; Models, Economic; Molecular Imaging; Nortropanes; Parkinson Disease; Program Evaluation; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; United States

The association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD.. Thirty-eight de novo, drug naïve PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, (123)I-FP-CIT-SPECT and (18)F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD.. On first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015).. PD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.

Topics: Aged; Brain; Female; Fluorodeoxyglucose F18; Functional Neuroimaging; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Positron-Emission Tomography; REM Sleep Behavior Disorder; Tomography, Emission-Computed, Single-Photon; Tropanes

We applied a simple isocontour volume-of-interest (VOI) method to analyze the whole striatum in an F-18 FP-CIT PET image and to investigate the usefulness of the method in differentiating healthy subjects from idiopathic Parkinson's disease (IPD) patients and the correlation of the value of functional volume parameters with the motor symptoms in patients with IPD.. Forty-three IPD patients and 23 age-matched healthy controls underwent F-18 FP-CIT PET. Using a dedicated workstation, VOIs for the whole striatum were drawn automatically with the gradient delineation method. The SUVmax, SUVmean, functional volume (FV), striatal volume activity (SVA), striatal-specific binding (SSB), and volume-specific uptake ratio (VSUR) were compared between the IPD patients and the normal subjects. In the IPD patients, the correlation between the clinical factor and the functional parameters was assessed.. The SUVmax, SUVmean, FV, SVA, SSB, and VSUR were significantly lower in the IPD patients than in the normal subjects. In the receiver operating characteristic analysis, those parameters had significant and good-to-excellent accuracy. In the patients with IPD, a moderate negative correlation was revealed between the SUVmax and H&Y stage, the SUVmean and H&Y stage, SVA and H&Y stage, the VSUR and H&Y stage, the FV and bradykinesia, and the SVA and bradykinesia.. The functional volumetric analysis of the striatum based on simple isocontour VOI was a useful method of analyzing the F-18 FP-CIT PET image. Not only can it be easily applied in daily clinical practice, but it can also be used as a clinical parameter to discriminate IPD and to correlate it with the disease severity.

Topics: Aged; Biological Transport; Case-Control Studies; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Retrospective Studies; Tropanes

To explore the microstructural integrity of the optic nerve and its role as a cognitive predictor in patients with de novo Parkinson's disease (PD) using diffusion tensor image-based magnetic resonance scans.. We enrolled 82 patients with de novo PD, 36 patients with drug-induced parkinsonism (DIP), and 36 controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured on the mid-portion of the intraorbital optic nerve. Using a multivariate analysis of variance with repeated measures, longitudinal changes in cognitive subscores of a comprehensive neuropsychological test were evaluated in PD patients according to optic nerve integrity.. The mean FA value in PD was significantly lower (0.552 ± 0.103, p < 0.001) than that in DIP (0.645 ± 0.099) or the controls (0.689 ± 0.089), whereas the mean ADC value was significantly higher in the PD group compared to the DIP or control group (p < 0.001). Optic nerve integrity was not associated with parkinsonian motor severity, striatal dopamine transporter activity, olfaction, or baseline cognitive performance in PD patents. In a longitudinal assessment of cognition in PD, the lower FA group showed significant decline in the performance of Clock Drawing Test (F = 3.39, p = 0.038), but no significant differences in the other cognitive subsets.. This study demonstrated that microstructural integrity in the optic nerve was distorted in PD patients, and that this nerve integrity might act as a cognitive predictor of visuospatial dysfunction.

Topics: Aged; Anisotropy; Cognition Disorders; Diffusion Tensor Imaging; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Neuropsychological Tests; Optic Nerve; Parkinson Disease; Positron-Emission Tomography; Retrospective Studies; Spatial Processing; Statistics as Topic; Tropanes

We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis.. Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome.. SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Diagnostic Errors; Dopamine; Dopaminergic Neurons; Female; Humans; Male; Middle Aged; Neurodegenerative Diseases; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tremor

(123)I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS. This study included 392 consecutive patients with degenerative parkinsonism undergoing (123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy. PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high specificity of 84-90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases.

Topics: Aged; Brain; Diagnosis, Differential; Dopamine; Dopaminergic Neurons; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

In this paper, we presented a novel reference-region-based (noninvasive) bi-graphical analysis for the quantification of a reversible radiotracer binding that may be too slow to reach relative equilibrium (RE) state during positron emission tomography (PET) scans. The proposed method indirectly implements the noninvasive Logan plot, through arithmetic combination of the parameters of two other noninvasive methods and the apparent tissue-to-plasma efflux rate constant for the reference region ([Formula: see text]). We investigated its validity and statistical properties, by performing a simulation study with various noise levels and [Formula: see text] values, and also evaluated its feasibility for [

Topics: Adult; Aged; Algorithms; Brain; Case-Control Studies; Computer Simulation; Feasibility Studies; Humans; Image Interpretation, Computer-Assisted; Kinetics; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Tropanes

Pure akinesia with gait freezing (PAGF) is a clinical syndrome characterized by freezing of gait, handwriting, and speech without abnormal eye movement or cognitive impairment. Several studies have suggested that PAGF may be a variant of progressive supranuclear palsy (PSP). However, the characteristics of striatal dopamine transporter loss in PAGF are unknown.. To investigate the subregional pattern of striatal dopamine transporter loss in patients with PAGF in comparison with patients with PSP and those with Parkinson disease (PD).. This retrospective case-control study included 15 patients with PAGF, 27 with PD, 20 with PSP, and 11 healthy controls who underwent F-18-fluorinated-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (18F FP-CIT) positron emission tomography between September 1, 2008, and July 31, 2014. The positron emission tomographic images were analyzed with 12 striatal subregional and 1 occipital volume-of-interest templates. The specific to nonspecific binding ratio (SNBR) and intersubregional ratio (ISR) in patients with PAGF were compared with those in patients with PD and those with PSP.. Comparisons of SNBRs of striatal subregions and ISR among patients with PAGF, PD, and PSP and healthy controls.. The mean (SD) SNBRs (1.4 [0.7]) of the whole striatum in the 15 patients with PAGF (mean [SD] age, 71.4 [6.6] years; 7 men and 8 women) were similar to those in the 20 patients (mean [SD] age, 70.6 [4.5] years; 11 men and 9 women) with PSP (1.5 [0.5]) but significantly lower than those in the 27 patients (mean [SD] age, 67.7 [5.3] years; 10 men and 17 women) with PD (3.0 [1.3]). The mean (SD) SNBRs of the caudate nuclei in patients with PAGF (1.3 [0.9]) were significantly lower than those in patients with PD (3.5 [1.5]; P < .001) but slightly higher than those in patients with PSP (1.2 [0.5]). The mean [SD] anterior caudate to ventral striatum ISRs in patients with PAGF (0.5 [0.3]) were similar to those in patients with PSP (0.4 [0.2]) but not in patients with PD (1.0 [0.2]). The mean (SD) posterior to anterior putamen ISRs in patients with PAGF (0.4 [0.2]) were similar to those in patients with PD (0.5 [0.2]) and those with PSP (0.4 [0.2]).. On 18F FP-CIT positron emission tomography, patients with PAGF show a pattern of preferential dopaminergic loss similar to that seen in patients with PSP. These results suggest a similar distribution of regional neuronal loss in the substantia nigra pars compacta between PAGF and PSP. This finding may be one of the pathophysiological results suggesting that PAGF is a phenotypic variant of PSP.

Topics: Aged; Case-Control Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Gait Disorders, Neurologic; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease; Pars Compacta; Positron-Emission Tomography; Supranuclear Palsy, Progressive; Syndrome; Tropanes

The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET).. We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up.. From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement (Cohen's kappa coefficient: 0.83, 95% CI 0.68-0.97, p < 0.001).. TCS and DaTSCAN have similar diagnostic accuracy for the diagnosis of early stage PD versus ET.

Topics: Diagnosis, Differential; Essential Tremor; Humans; Nortropanes; Parkinson Disease; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Doppler, Transcranial

Dopamine transporter (DAT) SPECT imaging is increasingly utilized for diagnostic purposes in suspected Parkinsonian syndromes. We performed a cross-sectional study to investigate whether assessment of texture in DAT SPECT radiotracer uptake enables enhanced correlations with severity of motor and cognitive symptoms in Parkinson's disease (PD), with the long-term goal of enabling clinical utility of DAT SPECT imaging, beyond standard diagnostic tasks, to tracking of progression in PD. Quantitative analysis in routine DAT SPECT imaging, if performed at all, has been restricted to assessment of mean regional uptake. We applied a framework wherein textural features were extracted from the images. Notably, the framework did not require registration to a common template, and worked in the subject-native space. Image analysis included registration of SPECT images onto corresponding MRI images, automatic region-of-interest (ROI) extraction on the MRI images, followed by computation of Haralick texture features. We analyzed 141 subjects from the Parkinson's Progressive Marker Initiative (PPMI) database, including 85 PD and 56 healthy controls (HC) (baseline scans with accompanying 3 T MRI images). We performed univariate and multivariate regression analyses between the quantitative metrics and different clinical measures, namely (i) the UPDRS (part III - motor) score, disease duration as measured from (ii) time of diagnosis (DD-diag.) and (iii) time of appearance of symptoms (DD-sympt.), as well as (iv) the Montreal Cognitive Assessment (MoCA) score. For conventional mean uptake analysis in the putamen, we showed significant correlations with clinical measures only when both HC and PD were included (Pearson correlation

Topics: Aged; Analysis of Variance; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nortropanes; Parkinson Disease; Psychiatric Status Rating Scales; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

The study's objective was to develop diagnostic predictive models using data from two commonly used [(123)I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis.. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [(123)I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [(123)I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed.. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [(123)I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [(123)I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %.. The predictive models built with ROI data and SPM data from [(123)I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres.

Topics: Aged; Aged, 80 and over; Artificial Intelligence; Diagnosis, Differential; Female; Humans; Image Processing, Computer-Assisted; Male; Parkinson Disease; Parkinson Disease, Secondary; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Among the cardinal parkinsonian motor deficits, the severity of bradykinesia correlates with striatal dopamine loss. However, the impact of regional striatal dopamine loss on specific components of bradykinesia remains unknown. Using gyroscopes, we measured the amplitude, speed, and frequency of finger tapping in 24 untreated patients with Parkinson's disease (PD) and 28 healthy controls. Using positron emission tomography (PET) studies and [(18)F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) in PD patients, we investigated the relationship between the mean values, variability and decrements of various kinematic parameters of finger tapping on one side (e.g. the mean, variability and decrement) and contralateral striatal FP-CIT binding. Compared with controls, PD patients had reduced amplitudes and speeds of tapping and showed greater decrement in those parameters. PD patients also exhibited greater irregularity in amplitude, speed, and frequency. Putaminal FP-CIT uptake levels correlated with the mean speed and amplitude, and caudate uptake levels correlated with mean amplitude. The variability of amplitude and speed correlated only with the caudate uptake levels. Neither caudate nor putaminal uptake correlated with frequency-related parameters or decrement in amplitude or speed. Reduced amplitude and speed of repetitive movement may be related to striatal dopaminergic deficit. Dopaminergic action in the caudate nucleus is required to maintain consistency of amplitude and speed. Although decrement of amplitude and speed is known to be specific for PD, we found that it did not mirror the degree of striatal dopamine depletion.

Topics: Accelerometry; Adult; Aged; Aged, 80 and over; Biomechanical Phenomena; Corpus Striatum; Dopamine; Fingers; Functional Laterality; Humans; Middle Aged; Motor Activity; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

Diagnosing Parkinson's disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations.. We aimed to investigate the relationship between serum UA levels and DaT availability in newly diagnosed, drug-naïve PD patients, by means of semiquantitative [(123) I]FP-CIT-SPECT.. We recruited 52 newly diagnosed, drug-naïve PD patients, and performed serum UA dosage and [(123) I]FP-CIT-SPECT.. Pearson's correlation analysis showed that UA levels were significantly higher in patients with higher averaged, ipsilateral and contralateral DaT binding in caudate, putamen, and striatum.. We showed, for the first time, by regional semiquantitative analysis of DaT binding in PD patients that UA levels significantly correlates with the severity of dopaminergic impairment in caudate, putamen, and striatum. This study broadens our knowledge on the importance of UA as a biomarker of PD.

Topics: Adult; Aged; Biomarkers; Dopamine Plasma Membrane Transport Proteins; Early Diagnosis; Female; Humans; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes; Uric Acid

We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET.. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells.. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls.. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation.. • Mesenchymal stem cells were intravenously injected to treat the PD rats • Dopamine transporter binding activity was improved after stem cell therapy • Stem cell therapy induced functional recovery and preservation of dopaminergic neurons • The effect of stem cells was confirmed by FP-CIT PET.

Topics: Animals; Bone Marrow Transplantation; Disease Models, Animal; Dopamine Plasma Membrane Transport Proteins; Male; Mesenchymal Stem Cell Transplantation; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Treatment Outcome; Tropanes

Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task.. Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks.. PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network.. These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits.

Topics: Adult; Aged; Brain; Brain Mapping; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Neural Pathways; Neuropsychological Tests; Parkinson Disease; Radiopharmaceuticals; Signal Processing, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tropanes

We investigated the striatal and extrastriatal DAT availability (SPM8) by [(123)I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p < 0.05) lower tracer binding in PD with depression was found in left cingulate cortex, persistent after correction for age, disease severity and duration, and inversely correlated with depression scores (r -0.336, p < 0.05). Our data indicate a significant association between PD depression and cingulate dopaminergic denervation supporting the dopaminergic hypothesis of PD depression.

Topics: Aged; Brain Mapping; Caudate Nucleus; Depressive Disorder; Dopamine; Gyrus Cinguli; Humans; Parkinson Disease; Putamen; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Mild cognitive impairment (MCI) is a common feature in Parkinson's disease (PD). We performed an exploratory study to investigate dopaminergic nigrostriatal innervation and its cognitive correlates in early untreated PD patients with MCI as compared to cognitively intact patients.. A consecutive series of 34-de-novo, drug-naïve patients with PD were enrolled. They underwent [123-I] FP-CIT SPECT and comprehensive neuropsychological battery. MCI was identified in 15 of 34 patients with PD.. The two groups did not show any statistically significant difference in age, sex, disease duration, education, lateralization, and H&Y and Hospital Anxiety and Depression Scale scores. Logistic regression analysis showed that UPDRS-III was weakly associated with MCI (P = 0.034). Partial correlation analysis controlling for UPDRS-III and age suggested that in PD patients with MCI reduced V3″ values in the more affected caudate were correlated with reduced performances in frontal assessment battery, Trail Making Test: part B minus Part A and copy task of the Rey-Osterrieth complex figure test. Reduced V3″ values in the more and less affected putamen were significantly related with reduced performance in frontal assessment battery and in copy task of Rey-Osterrieth complex figure test, respectively. No correlation was found between neuropsychological scores and DAT availability in PD patients without MCI.. Although preliminary, our results suggest that striatal dopamine depletion may contribute to some cognitive deficit in early never treated PD patients with MCI.

Topics: Aged; Cognitive Dysfunction; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychiatric Status Rating Scales; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of the present study was to develop a fully-automated computational solution for computer-aided diagnosis in Parkinson syndrome based on [(123)I]FP-CIT single photon emission computed tomography (SPECT) images.. A dataset of 654 [(123)I]FP-CIT SPECT brain images from the Parkinson's Progression Markers Initiative were used. Of these, 445 images were of patients with Parkinson's disease at an early stage and the remainder formed a control group. The images were pre-processed using automated template-based registration followed by the computation of the binding potential at a voxel level. Then, the binding potential images were used for classification, based on the voxel-as-feature approach and using the support vector machines paradigm.. The obtained estimated classification accuracy was 97.86%, the sensitivity was 97.75% and the specificity 98.09%.. The achieved classification accuracy was very high and, in fact, higher than accuracies found in previous studies reported in the literature. In addition, results were obtained on a large dataset of early Parkinson's disease subjects. In summation, the information provided by the developed computational solution potentially supports clinical decision-making in nuclear medicine, using important additional information beyond the commonly used uptake ratios and respective statistical comparisons. (ClinicalTrials.gov Identifier: NCT01141023).

Topics: Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Molecular Imaging; Parkinson Disease; Pattern Recognition, Automated; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Support Vector Machine; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to evaluate the impact of DaTscan in a heterogeneous group of patients with movement disorders as well as the degree of confidence in scan findings between different readers.. A retrospective evaluation of consecutive patients who underwent DaTscan during 1 year was performed. The patients' demographics, symptoms, duration, clinical diagnosis, and medications were collected. The scan findings were categorized by 2 blinded observers on a semiquantitative scale as follows: 0, normal; 1, mild; 2, moderate; 3, marked; and 4, absent uptake for each of the caudate heads and putamina separately. A correlation of the scan findings with the clinical symptoms and diagnosis as well as interobserver agreement was performed. Disagreement was considered when a difference greater than 2 in more than 1 area of the basal ganglia was recorded. Descriptive statistics and κ test for interobserver agreement were used for data analysis.. Fifty-seven patients were included (mean age, 63.4 years; 29 men, 28 women). Clinical diagnosis of Parkinson disease (PD) was certain in 26 and uncertain in 31 patients. DaTscan was markedly abnormal in 24 (92%) of 26 patients with certain clinical diagnosis of PD and normal in the remaining 2 (8%). In 31 patients with uncertain diagnosis, 15 (48%) had markedly abnormal scans, 5 (16%) had mild abnormalities, and 11 (36%) had normal scans. Each of the sensitivity and positive predictive value of DaTscan in patients who had certain clinical diagnosis of PD (26 patients) is 92%. Interobserver agreement occurred in 52 (91%) of 57 scans and disagreement in 5 (9%) of 57 (κ = 0.82). There was also a good correlation with laterality of symptoms in 32 (82%) of 39 positive studies.. Markedly abnormal DaTscan is confirmed as the diagnostic pattern for PD. This pattern helps confirm the diagnosis in patients with unclear clinical diagnosis. Good interobserver agreement is easily obtained in reading DaTscans.

Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

To investigate the correlation between the striatal three-dimensional location and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the context of idiopathic Parkinson's disease (PD) through radiolabeled N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane positron emission tomography/computed tomography (FP-CIT PET/CT).. In this cross-sectional study, we assessed the UPDRS motor score and performed FP-CIT PET/CT in patients with PD. Thirty-eight patients with idiopathic PD [average 70 years of age (range 49-86); male:female ratio 12:26] were enrolled. The correlation between FP-CIT PET/CT and the UPDRS III scores was investigated after the transformation of PET images by an alternative method using MATLAB.. Left caudate nucleus uptake negatively correlated with UPDRS items 18, 20 (face), 22 (right arm and leg), 23, 24 (right side), 26 (right side), 27, 30, and 31, while right caudate nucleus uptake positively correlated with items 18, 22 (left arm), 26, and 29. Putamen uptake correlated with items 22 and 25. Left caudate nucleus uptake positively correlated with axial and akinetic-rigidity symptoms.. FP-CIT uptake in specific basal ganglia structures strongly correlated with the UPDRS III motor score. Among these, the left caudate nucleus exhibited the strongest relationship with axial and akinetic-rigidity PD symptoms.

Topics: Aged; Aged, 80 and over; Brain; Cross-Sectional Studies; Female; Fluorodeoxyglucose F18; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Movement Disorders; Multimodal Imaging; Parkinson Disease; Positron-Emission Tomography; Retrospective Studies; Tomography, X-Ray Computed; Tropanes

Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease.. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain.. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05.. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease.

Topics: Aged; Case-Control Studies; Dopamine; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Ligands; Male; Mesencephalon; Middle Aged; Parkinson Disease; Raphe Nuclei; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins; Thalamus; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tropanes

Decreased myocardial uptake of I-123 metaiodobenzylguanidine (MIBG) is an important finding for diagnosis of Parkinson's disease (PD). This study compared I-123 MIBG SPECT and planar imaging with regard to their diagnostic yield for PD. 52 clinically diagnosed PD patients who also had decreased striatal uptake on FP-CIT PET/CT were enrolled. 16 normal controls were also included. All underwent cardiac MIBG planar scintigraphy and SPECT separately. Myocardial I-123 MIBG uptake was interpreted on planar and SPECT/CT images separately by visual and quantitative analysis. The final diagnosis was made by consensus between two readers. Kappa analyses were performed to determine inter-observer agreement for both methods. Sensitivity, specificity, and accuracy were compared with McNemar's test. The sensitivity, specificity, and accuracy were 84.6, 100, and 88.2% for planar images and 96.2, 100 and 97.1% for SPECT, respectively, with a significant difference between the two imaging methods (p < 0.031). All inter-observer agreements were almost perfect (planar scintigraphy: κ = 0.82; SPECT: κ = 0.93). Heart-to-mediastinum ratios from PD patients with negative planar and positive SPECT scans (group A) and patients with positive planar and positive SPECT scans (group B) were 1.69 ± 0.16 (1.59-1.85) and 1.41 ± 0.15 (1.20-1.53), respectively, and showed significant difference (p = 0.023). Lung-to-mediastinum ratios for groups A and B were 2.16 ± 0.20 (1.96-2.37) and 1.6 ± 0.19 (1.3-1.78), respectively, and were significantly higher in the former (p = 0.001). I-123 MIBG SPECT has a significantly higher diagnostic performance for PD than planar images. Increased lung uptake may cause false-negative results on planar imaging.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Female; Heart; Humans; Male; Middle Aged; Parkinson Disease; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross-sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics.. Seventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow-up). We assessed task performance longitudinally in both groups; at follow-up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta-analyses to localize regions-of-interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group-by-task analyses and within-group regression analyses of planning-related neural activation. We studied task-related functional connectivity of seeds in the DLPFC and caudate nucleus.. PD patients, compared with controls, showed impaired task performance at both time-points, while both groups showed similar performance reductions from baseline to follow-up. Compared to controls, patients showed lower planning-related brain activation together with decreased functional connectivity.. These findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task-related brain activity and connectivity.

Topics: Brain; Brain Mapping; Cross-Sectional Studies; Dopamine Plasma Membrane Transport Proteins; Executive Function; Female; Follow-Up Studies; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Neuropsychological Tests; Parkinson Disease; Problem Solving; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

As an indicator of synchronous neural activity, resting-state functional networks are influenced by neuropathological and neurochemical changes in degenerative diseases. To further advance understanding about neurochemical and neuropathological basis for resting-state functional maps, we performed a comparative analysis of resting-state functional connectivity in patients with Parkinson's disease (PD) and drug induced parkinsonism (DIP). Resting-state neuroimaging data were analyzed with a seed-based approach to investigate striatocortical functional connectivity and cortical functional connectivity within the default mode network, executive control network, and the dorsal attention network. The striatal subregions were divided into the more or less affected sides in terms of dopamine transporter uptake. Compared with DIP, PD exhibited an increased cerebellar connectivity from the more affected side of the caudate and the less affected sides of the anterior and the posterior putamen. Additionally, PD showed increased functional connectivity in the anterior prefrontal areas from the more affected side of the anterior putamen and from the less affected side of the posterior putamen. However, PD exhibited decreased cortical functional connectivity from the posterior cingulate cortex in the left temporal area. Finally, DIP patients showed decreased cortical functional connectivity from the dorsolateral prefrontal cortex in frontal and parietal areas compared with PD patients. In summary, the present study demonstrates that PD patients exhibited a unique resting state functional connectivity that may be associated with PD-related pathological changes beyond the dopaminergic system, whereas DIP patients showed altered functional connectivity within executive control network.

Topics: Aged; Brain Mapping; Corpus Striatum; Dopamine; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Neural Pathways; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Substantia Nigra; Tropanes

Spatial normalization is a prerequisite step for analyzing positron emission tomography (PET) images both by using volume-of-interest (VOI) template and voxel-based analysis. Magnetic resonance (MR) or ligand-specific PET templates are currently used for spatial normalization of PET images. We used computed tomography (CT) images acquired with PET/CT scanner for the spatial normalization for [18F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane (FP-CIT) PET images and compared target-to-cerebellar standardized uptake value ratio (SUVR) values with those obtained from MR- or PET-guided spatial normalization method in healthy controls and patients with Parkinson's disease (PD).. We included 71 healthy controls and 56 patients with PD who underwent [18F]-FP-CIT PET scans with a PET/CT scanner and T1-weighted MR scans. Spatial normalization of MR images was done with a conventional spatial normalization tool (cvMR) and with DARTEL toolbox (dtMR) in statistical parametric mapping software. The CT images were modified in two ways, skull-stripping (ssCT) and intensity transformation (itCT). We normalized PET images with cvMR-, dtMR-, ssCT-, itCT-, and PET-guided methods by using specific templates for each modality and measured striatal SUVR with a VOI template. The SUVR values measured with FreeSurfer-generated VOIs (FSVOI) overlaid on original PET images were also used as a gold standard for comparison.. The SUVR values derived from all four structure-guided spatial normalization methods were highly correlated with those measured with FSVOI (P < 0.0001). Putaminal SUVR values were highly effective for discriminating PD patients from controls. However, the PET-guided method excessively overestimated striatal SUVR values in the PD patients by more than 30% in caudate and putamen, and thereby spoiled the linearity between the striatal SUVR values in all subjects and showed lower disease discrimination ability. Two CT-guided methods showed comparable capability with the MR-guided methods in separating PD patients from controls and showed better correlation between putaminal SUVR values and the parkinsonian motor severity than the PET-guided method.. CT-guided spatial normalization methods provided reliable striatal SUVR values comparable to those obtained with MR-guided methods. CT-guided methods can be useful for analyzing dopamine transporter PET images when MR images are unavailable.

Topics: Aged; Cerebellum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiography; Tropanes

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression,

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cohort Studies; Female; Humans; Male; Middle Aged; Occipital Lobe; Parkinson Disease; Raphe Nuclei; Serotonin; Serotonin Plasma Membrane Transport Proteins; Severity of Illness Index; Statistics as Topic; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

Topics: Aged; alpha-Synuclein; Cognition Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Gene Expression Regulation; Genetic Testing; Humans; Male; Microarray Analysis; Middle Aged; Neuroimaging; Parkinson Disease; Radionuclide Imaging; RNA, Messenger; Severity of Illness Index; Tropanes

Serum urate levels have been associated with risk for and progression of Parkinson's disease (PD). Urate-related compounds are therapeutic candidates in neuroprotective efforts to slow PD progression. A urate-elevating agent is currently under investigation as a potential disease-modifying strategy in people with PD. However, PD is a heterogeneous disorder, and genetic variation may explain divergence in disease severity and progression.. We conducted a genome-wide association study to identify gene variant × serum urate interaction effects on the striatal (123) I-ioflupane (DaTscan) binding ratio measured using single photon emission computed tomography in patients with possible PD from the Parkinson's Progression Markers Initiative (PPMI, n = 360). Follow-up analyses were conducted to assess gene variant × serum urate interaction effects on magnetic resonance imaging-derived regional brain volumes and clinical status. We then attempted to replicate our primary analysis in patients who entered the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) with a clinical diagnosis of PD (n = 349).. Rs1109303 (T>G) variant within the INPP5K gene on chromosome 17p13.3 demonstrated a genome-wide significant interaction with serum urate level to predict striatal dopamine transporter density among all PPMI participants (n = 359) with possible PD (p = 2.01 × 10(-8) ; after excluding participants with SWEDD [scan without evidence of dopaminergic deficit]: p = 1.12 × 10(-9) ; n = 316). Independent of striatal dopamine transporter density, similar effects on brain atrophy, bradykinesia, anxiety, and depression were observed. No effect was present in the PRECEPT sample at baseline; however, in non-SWEDD PD participants in PRECEPT (n = 309), we observed a significant longitudinal genotype × serum urate interaction effect, consistent in direction with the PPMI sample, on progression of striatal dopamine transporter density over the 22-month follow-up.. Genetic profile combined with serum urate level can be used to predict disease severity and potential disease progression in patients with PD. These results may be relevant to therapeutic efforts targeting the urate pathway.

Topics: Adult; Aged; Aged, 80 and over; Behavior; Corpus Striatum; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Genome-Wide Association Study; Humans; Inositol Polyphosphate 5-Phosphatases; Magnetic Resonance Imaging; Male; Middle Aged; Nortropanes; Parkinson Disease; Phosphoric Monoester Hydrolases; Predictive Value of Tests; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Uric Acid

Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD.. In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by [(123)I]FP-CIT SPECT tracer binding to the dopamine transporter (DaT).. Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients.. These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.

Topics: Aged; Caudate Nucleus; Cross-Sectional Studies; Depression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Putamen; Radionuclide Imaging; Retrospective Studies; Tropanes

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density.. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests.. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls.. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Topics: Case-Control Studies; Corpus Striatum; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Radionuclide Imaging; Tropanes

Topics: Aged; Atrophy; Cerebral Amyloid Angiopathy; Corpus Striatum; Humans; Iodine Radioisotopes; Male; Mesencephalon; Neuroimaging; Nortropanes; Parkinson Disease; Radionuclide Imaging; Supranuclear Palsy, Progressive

Presynaptic dopaminergic deficiency on dopamine transporter imaging supports a clinical diagnosis of Parkinson's disease and correlates with the severity of rigidity and bradykinesia. Baseline dopaminergic deficiency predicts clinical severity, but the relationship with subsequent medication use has not been reported.. A randomly selected cross section of 83 Parkinson's disease (PD) patients who had [(123) I] FP-CIT SPECT at the time of clinical diagnosis was identified. Dopaminergic deficiency was graded 1, 2 or 3 with increasing severity using visual assessment and by semiquantitative analysis of putamen and caudate uptake. Antiparkinson medication usage and clinical severity by Hoehn and Yahr were noted annually to 3 years.. In 83 patients (66% male, median age 65.0 years, IQ 55.4-71.8), [(123) I]FP-CIT SPECT was grade 1 in 20 (24%), grade 2 in 53 (64%) and grade 3 in 10 patients (12%). Dopamine transporter uptake ratios were inversely associated with antiparkinson medication usage (r = -0.26, P = 0.0201) and Hoehn Yahr stage (r = -0.32, P = 0.0029) at 3 years from baseline, but there was considerable variation in drug usage in individual patients. At 3 years, patients with grade 1 scans at baseline received a median dose of 325 levodopa equivalent units (LEU) (interquartile range 175-433); grade 2 scan patients 400 LEU (interquartile range 300-635); and grade 3 scan patients 460 LEU (interquartile range 252-658).. The degree of reduction in presynaptic dopaminergic uptake at baseline is associated with higher antiparkinson drug dosage at follow-up, but the wide variation means that the baseline FP-CIT SPECT does not reliably predict drug use in individual cases.

Topics: Aged; Antiparkinson Agents; Female; Humans; Levodopa; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Putamen; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinson's disease (PD).. A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised manners.. Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects.. A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.

Topics: Antiparkinson Agents; Brain Mapping; Corpus Striatum; Disruptive, Impulse Control, and Conduct Disorders; Dopamine; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

The purpose of the current paper is to present a computational solution to accurately quantify a specific to a non-specific uptake ratio in [123I]fP-CIT single photon emission computed tomography (SPECT) images and simultaneously measure the spatial dimensions of the basal ganglia, also known as basal nuclei. A statistical analysis based on a reference dataset selected by the user is also automatically performed.. The quantification of the specific to non-specific uptake ratio here is based on regions of interest defined after the registration of the image under study with a template image. The computational solution was tested on a dataset of 38 [123I]FP-CIT SPECT images: 28 images were from patients with Parkinson's disease and the remainder from normal patients, and the results of the automated quantification were compared to the ones obtained by three well-known semi-automated quantification methods.. The results revealed a high correlation coefficient between the developed automated method and the three semi-automated methods used for comparison (r ≥0.975). The solution also showed good robustness against different positions of the patient, as an almost perfect agreement between the specific to non-specific uptake ratio was found (ICC=1.000). The mean processing time was around 6 seconds per study using a common notebook PC.. The solution developed can be useful for clinicians to evaluate [123I]FP-CIT SPECT images due to its accuracy, robustness and speed. Also, the comparison between case studies and the follow-up of patients can be done more accurately and proficiently since the intra- and inter-observer variability of the semi-automated calculation does not exist in automated solutions. The dimensions of the basal ganglia and their automatic comparison with the values of the population selected as reference are also important for professionals in this area.

Topics: Aged; Algorithms; Automation; Basal Ganglia; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Observer Variation; Parkinson Disease; Reproducibility of Results; Signal Processing, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tropanes

Vascular parkinsonism (VP) may occur as a distinct clinicopathological entity but the comorbid presence of vascular damage in Parkinson's disease (PD) is very frequent too. This differential diagnosis has therapeutic and prognostic implications but remains challenging as the usefulness of a number of supporting tools is still controversial.. To ascertain the clinical value of cardiac (123)I-meta-iodobenzylguanidine ((123)I-MIBG) SPECT, olfactory function and (123)I-FP-CIT SPECT as supporting tools in the differential diagnosis between VP and PD.. Cross-sectional study of 15 consecutive patients with suspected VP, 15 PD patients and 9 healthy subjects. Cardiac (123)I-MIBG SPECT (heart-to-mediastinum ratio) and olfactory testing (University of Pennsylvania Smell Identification Test-UPSIT) were performed in all of them. (123)I-FP-CIT SPECT was performed in VP-suspected patients.. Heart-to-mediatinum ratio was significant lower in suspected VP (mean 1.45) and PD (mean 1.16) compared to control group (mean 1.69) (p = 0.017 and p < 0.0001). VP patients presented a higher ratio than PD patients (p = 0.001). Control group presented a significant higher UPSIT score (mean 30.71) when compared to both VP (mean 18.33) and PD (mean 15.29) (p = 0.001 for both groups). Those VP with a cardiac (123)I-MIBG non suggestive of PD were more likely to have a higher UPSIT score (p = 0.006). (123)I-FP-CIT SPECT imaging was heterogeneous (7/15 VP normal, 3/15 abnormal suggestive of PD and 5/15 abnormal but atypical for PD).. The use of cardiac (123)I-MIBG SPECT and to a lesser extent UPSIT could assist the differential diagnosis between VP and PD in subjects in which the diagnosis remains uncertain despite (123)I-FP-CIT SPECT imaging.

Topics: 3-Iodobenzylguanidine; Aged; Cross-Sectional Studies; Diagnosis, Differential; Female; Heart; Humans; Male; Parkinson Disease; Parkinson Disease, Secondary; Radiopharmaceuticals; Smell; Tomography, Emission-Computed, Single-Photon; Tropanes

An 80-year-old man with Parkinson disease underwent DaTscan imaging, which showed no detectable uptake in the basal ganglia but normal background uptake in other parts of the brain and in the chest and abdomen. It was later found that the patient was taking methylphenidate. The second study performed 3 weeks later after discontinuing methylphenidate for 48 hours showed good uptake in the striatum. Our results indicate that methylphenidate may completely block physiologic uptake of DaTscan in the striatum and that this effect can be effectively reversed after discontinuing the medication for a short period.

Topics: Aged, 80 and over; Humans; Male; Methylphenidate; Neostriatum; Nortropanes; Parkinson Disease; Radionuclide Imaging

Prepulse inhibition is a measure of sensorimotor gating, which reflects the ability to filter or 'gate' irrelevant information. Prepulse inhibition is dramatically altered in basal ganglia disorders associated with dysfunction in the midbrain dopaminergic system, and corresponding cognitive information processing deficits such as slowed processing speed. Parkinson's disease is characterised by the degeneration of the midbrain dopaminergic system and is associated with cognitive dysfunction, including slowed information processing. Although sensorimotor processes in Parkinson's disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function.. We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I-FP-CIT-SPECT scanning, in patients with Parkinson's disease.. 38 Parkinson patients were assessed with prepulse inhibition, neuropsychological tests, and neurological investigation. A subset of these patients underwent 123I-FP-CIT-SPECT scanning.. Patients with a higher level of prepulse inhibition performed better on cognitive measures tapping attention and processing speed than patients with a lower level of prepulse inhibition. Furthermore, there were significant correlations between prepulse inhibition and 123I-FP-CIT uptake in the striatum.. Our results suggest that the level of prepulse inhibition is related to the efficiency of information processing in Parkinson's disease, and to the density of dopamine transporters in the striatum.

Topics: Aged; Attention; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Inhibition, Psychological; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Reflex, Startle; Sensory Gating; Tomography, Emission-Computed, Single-Photon; Tropanes

An automated objective striatal analysis (OSA) software program was applied to dopamine transporter (123)I-ioflupane images acquired on subjects with varying severities of parkinsonism. The striatal binding ratios (SBR) of the left and right putamina (relative to the occipital lobe) were computed, and the laterality of that measure was compared with clinical symptoms and visual reads. The objective over-read of OSA was evaluated as an aid in confirming the laterality of disease onset.. One hundred one (123)I-ioflupane scans were acquired on clinically referred subjects. SPECT images were analyzed using the OSA software, which locates the slices containing the striatal and background (occipital) structures, positions regions over the left and right caudate nuclei and putamina, and calculates the background-subtracted SBR. Seven images were uninterpretable because of patient motion or lack of visualization of the striatum. The remaining 94 scans were analyzed with OSA. Differences between left and right putaminal SBR ranged from 0% to 36.6%, with a mean of 11.4%. When the difference between the SBR of the left and right putamina was greater than 6%, the lower side was taken as the side of onset. Left-to-right differences less than 6% were considered to be nonlateralizing (symmetric). The 94 scans were reviewed independently by 3 masked expert readers. By majority consensus, abnormal findings were seen on 67 of the 94 scans, of which 46 had available clinical findings.. Clinically, 34 subjects presented with lateralized tremors and 12 with symmetric or no tremors. Of the 34 cases of clinically lateralized tremors, 26 (76%) were concordant with the OSA findings, 5 were disparate with OSA (15%), and in 3 the OSA results were symmetric (9%). For the same 34 patients, the visual reads were concurrent with clinical tremor findings in 24 cases (71%), 1 was disparate (3%), and 9 visual reads were symmetric (26%). Of the 9 scans deemed symmetric by readers, 4 were correctly lateralized by OSA, and of the 3 symmetric OSA results, 2 were correctly lateralized visually.. The OSA program may be a helpful aid in the interpretation of (123)I-ioflupane SPECT images for determining laterality representing the asymmetric loss of dopamine transporters in the striata. OSA offers an objective, reproducible over-read evaluation for the laterality of onset in Parkinson disease.

Topics: Adult; Aged; Aged, 80 and over; Biological Transport; Female; Humans; Male; Middle Aged; Neostriatum; Nortropanes; Parkinson Disease; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

To investigate whether the magnitude of presynaptic dopamine depletion is a risk factor for the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) by quantitatively analyzing (18)F-FP-CIT PET data.. This retrospective cohort study enrolled a total of 127 drug-naive de novo patients with PD who completed (18)F-FP-CIT PET scanning at their initial evaluation. The patients visited our outpatient clinic every 3-6 months and had been followed for a minimum of 2 years since beginning dopaminergic medication. The predictive power of the quantitatively analyzed (18)F-FP-CIT uptake of striatal subregions and other clinical factors for the development of LID was evaluated using Cox proportional hazard models.. During a mean follow-up period of 3.4 years, 35 patients with PD (27.6%) developed LID. Patients with LID showed less dopamine transporter (DAT) activity in the putamen than did those without LID. Multivariate Cox proportional hazard models revealed that the DAT uptakes of the anterior putamen (hazard ratio [HR] 0.530; p = 0.032), posterior putamen (HR 0.302; p = 0.024), and whole putamen (HR 0.386; p = 0.022) were significant predictors of the development of LID, whereas DAT activities in the caudate and ventral striatum were not significantly correlated with the development of LID. In addition, younger age at onset of PD and higher dose of levodopa were also significant predictors of the development of LID.. The present results provide convincing evidence that presynaptic dopaminergic denervation in PD plays a crucial role in the development of LID.

Topics: Aged; Antiparkinson Agents; Chi-Square Distribution; Cohort Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Predictive Value of Tests; Proportional Hazards Models; Tropanes

The pathogenesis of visual hallucinations (VHs) in Parkinson's disease (PD) has been considered multifactorial. In the pathophysiology of VHs a combination of impaired visual processing and attention has been reported. Imaging studies evidenced a role of the primary visual system and visual association areas as well as a dysfunctional activation of frontal areas in the occurrence of VHs. Due to the functional connections between basal ganglia and frontal areas, a role of basal ganglia and of the fronto-striatal circuits in the pathogenesis of VHs may be postulated. Aim of this study is to unveil whether a presynaptic dopamine deficiency at baseline may predict the development of VHs.. A group of 18 non demented PD patients with VHs was matched with 18 non demented PD patients without VHs as regards age of onset of disease, disease duration and severity and levodopa equivalent dose. We retrospectively analyzed the (123)I-FP CIT SPECT performed on the two groups at the onset of their disease. The striatal uptake values in the two groups were examined, in order to evaluate nigrostriatal differences between the groups with different behavioral phenotype.. The group of patients with VHs had a significant reduction (p < 0.05) in right caudate uptake values at baseline when compared with patients without VHs. No significant differences were found between the groups regarding left caudate and putaminal uptake values.. The frontal impairment reported in PD patients with VHs may be due to a right caudate dysfunction, as it is connected to the frontal brain areas via neuronal loops.

Topics: Aged; Caudate Nucleus; Denervation; Dopamine; Dopaminergic Neurons; Female; Hallucinations; Humans; Iodine Radioisotopes; Levodopa; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor.. [(123)I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates.. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen.. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.

Topics: Aged; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Protein Binding; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Topics: Aged; Brain; Creutzfeldt-Jakob Syndrome; Diffusion Magnetic Resonance Imaging; Electroencephalography; Female; Humans; Parkinson Disease; Synapses; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine-dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP-CIT positron emission tomography imaging and resting-state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine-dependent functional networks. The major finding is that the patterns of dopamine-dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine-dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine-dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine-dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine-dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian-related motor and cognitive performance.

Topics: Brain; Brain Mapping; Dopamine; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Oxygen; Parkinson Disease; Positron-Emission Tomography; Rest; Statistics as Topic; Tropanes

To verify if (123)I-FP-CIT, DaTSCAN(®) can differentiate early stages of Parkinson's disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinson's disease.. 128 consecutive patients were investigated with (123)I-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI.. In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking.. In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN(®) SPECT in this material.

Topics: Adult; Aged; Aged, 80 and over; Dopaminergic Neurons; Female; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Nerve Degeneration; Parkinson Disease; Radiopharmaceuticals; Severity of Illness Index; Software; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ₁₋₄₂ amyloid peptide and (123)I-FP-CIT uptake.. The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before (123)I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation.. Striatal (123)I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of (123)I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum that is contralateral to theside mainly affected on clinical examination (P<0.001) [corrected].No significant relationships were found between Aβ₁₋₄₂ amyloid peptide and (123)I-FP-CIT binding.. The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ₁₋₄₂ amyloid peptide seems not to be related to nigrostriatal degeneration in our series.

Topics: Aged; Amyloid beta-Peptides; Biomarkers; Dopamine; Female; Humans; Male; Parkinson Disease; Peptide Fragments; Phosphorylation; tau Proteins; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopamine transporter (DAT) imaging shows age-related decline of ligand binding in the normal striatum, a decline attributed to regulatory changes. We investigated if similar changes occur in the striatum of Parkinson's disease (PD) patients, using PET and [(18)F]FP-CIT, a ligand for DAT.. We performed [(18)F]FP-CIT PET in 39 drug-naïve, de novo PD patients (age 56.0 ± 11.6 years, mean ± SD) and 34 healthy control subjects (age 52.3 ± 17.8). Parkinsonism was assessed by UPDRS III and Purdue pegboard. Binding ratios of [(18)F]FP-CIT were obtained in the putamen and caudate using the occipital cortex as reference.. Mean [(18)F]FP-CIT binding ratios in PD were 3.76 ± 0.74 (mean ± SD) in the putamen and 6.80 ± 1.05 in the caudate nucleus, significantly smaller than those in the healthy control (9.20 ± 1.38, 8.66 ± 1.12, respectively; p < 0.001 vs. healthy control for both). Regression analysis of [(18)F]FP-CIT binding ratios on age in healthy subjects showed significant correlations in the putamen (p < 0.001) and caudate nucleus (p < 0.001). Similar analysis in PD patients also showed significant correlations in the putamen (p = 0.015) and caudate nucleus (p = 0.018). The slope of regression in the putamen was -0.061 in the healthy control and -0.017 in PD, with significant differences between the two groups (p = 0.0003). In contrast, the regression slope in the caudate nucleus was -0.040 in the healthy control group, and -0.032 in the PD group with no significant differences between the two groups.. Striatal [(18)F]FP-CIT binding showed significant age affects in patients with de novo PD after standardization for the severity of disease. The age effects were significantly smaller in PD patients than those in healthy subjects, but only in the putamen, not in the caudate nucleus. Given that age-related attrition of DA neurons is even in normal striatum, the uneven age effects in the parkinsonian striatum are likely to reflect the superimposition of disease-driven compensation on the aging effect.

Topics: Adult; Aged; Aging; Corpus Striatum; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Regression Analysis; Severity of Illness Index; Tropanes

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.

Topics: Adult; Aged; Aged, 80 and over; Cognition Disorders; Corpus Striatum; Cross-Sectional Studies; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

A progressive reduction in the speed and amplitude of repetitive action is an essential component of bradykinesia, which is called sequence effect (SE). Because SE is specific to Parkinson's disease (PD) and is suggested to be associated with motor arrest, its features are of great interest. The aim of this study was, for the first time, to find the neural correlates of SE and to demonstrate whether dopaminergic deficit is correlated with SE.. We enrolled 12 patients with de novo PD at a tertiary referral hospital. Correlations between SE severity and alterations in gray and white matter were studied. The association between severity of the SE and striatal dopaminergic deficits was also analyzed.. There was a significant negative correlation between the volumetric changes in the anterior cingulate cortex (ACC) and the inferior semilunar lobule of the cerebellum and the degree of SE. There was a significant correlation between the long association fibers (the superior longitudinal fasciculus, the uncinate fasciculus, and the inferior fronto-occipital fasciculus) connecting the frontal lobes to the temporal, parietal, and occipital lobes and SE. There was a significant negative correlation between SE in the more affected hand and the caudate dopamine transporter binding in the more affected hemisphere.. Our results suggest that the ACC and the cerebellum (inferior semilunar lobule) are associated with the severity of SE. Taken together with DTI findings, the present study proposes that ACC may have an important role. Our data show that the caudate dopaminergic activity may be related to SE.

Topics: Aged; Anisotropy; Brain Mapping; Cerebellum; Diffusion Tensor Imaging; Female; Gyrus Cinguli; Humans; Male; Middle Aged; Movement; Nerve Fibers, Myelinated; Parkinson Disease; Positron-Emission Tomography; Regression Analysis; Tropanes; Ultrasonography

SWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.. The Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.. The total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).. The patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.

Topics: Aged; Aged, 80 and over; Cocaine; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Quality of Life; Radiopharmaceuticals; Sleep Wake Disorders; Tropanes

This paper presents the analysis of the statistical significance in the selection of the ROI for the discriminant analysis of brain images to identify Parkinson patients or subjects without any pathology. The particular features and brain functional patterns of the Parkinson's disease cause that there are regions that conveniently reveal the presence of the pathology, in this case mainly the striatum region. The selection of the brain mask makes incidence in two main aspects: the selection of the region of interest (striatum and surrounding area) for the analysis, but also the selection of the region without significance, which is the reference area for the intensity normalization, previous to the analysis. This work studies the statistical significance in the selection of ROIs in 3D brain images for Parkinson, depending on the objective to be achieved in the posterior analysis process.

Topics: Algorithms; Corpus Striatum; Data Interpretation, Statistical; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

In this work, we perform a comparison between the spatial normalization of [123I]FP-CIT SPECT brain images when a FP-CIT SPECT and a MRI template are used. A 12-parameters affine registration model is calculated by the optimization of a sum of squares cost function. When the images are registered to a FP-CIT template, the intersubject variation is found to be lower than when the MRI template is used, specially in the striatum, which is the most relevant part of the brain in FP-CIT SPECT brain images.

Topics: Corpus Striatum; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Multimodal Imaging; Parkinson Disease; Pattern Recognition, Automated; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Tomography, Emission-Computed, Single-Photon; Tropanes

Brain single-photon-emission-computerized tomography (SPECT) with I-ioflupane (I-FP-CIT) is useful to diagnose Parkinson disease (PD). To investigate the diagnostic performance of I-FP-CIT brain SPECT with semiquantitative analysis by Basal Ganglia V2 software (BasGan), we evaluated semiquantitative data of patients with suspect of PD by a support vector machine classifier (SVM), a powerful supervised classification algorithm.I-FP-CIT SPECT with BasGan analysis was performed in 90 patients with suspect of PD showing mild symptoms (bradykinesia-rigidity and mild tremor). PD was confirmed in 56 patients, 34 resulted non-PD (essential tremor and drug-induced Parkinsonism). A clinical follow-up of at least 6 months confirmed diagnosis. To investigate BasGan diagnostic performance we trained SVM classification models featuring different descriptors using both a "leave-one-out" and a "five-fold" method. In the first study we used as class descriptors the semiquantitative radiopharmaceutical uptake values in the left (L) and right (R) putamen (P) and in the L and R caudate nucleus (C) for a total of 4 descriptors (CL, CR, PL, PR). In the second study each patient was described only by CL and CR, while in the third by PL and PR descriptors. Age was added as a further descriptor to evaluate its influence in the classification performance.I-FP-CIT SPECT with BasGan analysis reached a classification performance higher than 73.9% in all the models. Considering the "Leave-one-out" method, PL and PR were better predictors (accuracy of 91% for all patients) than CL and CR descriptors; using PL, PR, CL, and CR diagnostic accuracy was similar to that of PL and PR descriptors in the different groups. Adding age as a further descriptor accuracy improved in all the models. The best results were obtained by using all the 5 descriptors both in PD and non-PD subjects (CR and CL + PR and PL + age = 96.4% and 94.1%, respectively). Similar results were observed for the "five-fold" method. I-FP-CIT SPECT with BasGan analysis using SVM classifier was able to diagnose PD. Putamen was the most discriminative descriptor for PD and the patient age influenced the classification accuracy.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Nortropanes; Parkinson Disease; Retrospective Studies; Support Vector Machine; Tomography, Emission-Computed, Single-Photon

To identify plasma-based biomarkers for Parkinson disease (PD) risk.. In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity.. One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).. Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.

Topics: Age of Onset; Aged; Apolipoprotein A-I; Biomarkers; Cohort Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Motor Activity; Parkinson Disease; Risk Factors; Sex Factors; Statistics as Topic; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

To test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co-registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra-class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi-quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t-test, P < 0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P = 0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes.

Topics: Adult; Aged; Aged, 80 and over; Corpus Striatum; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Phantoms, Imaging; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

Prior evidence has suggested a link between caudate dopaminergic functioning and cognition in Parkinson's disease (PD). In this dual tracer study we analyzed the relationship between nigrostriatal dopaminergic dysfunction and the expression of the previously validated PD cognition-related metabolic pattern (PDCP). In this study, 17 non-demented PD patients underwent positron emission tomography (PET) imaging with [(18)F]-fluorodeoxyglucose to measure PDCP expression, and [(18)F]-fluoropropyl-β-CIT (FPCIT) to measure dopamine transporter (DAT) binding. Automated voxel-by-voxel searches of the FPCIT PET volumes were performed to identify regions in which DAT binding significantly correlated with PDCP expression values. The findings were validated using prespecified anatomical regions-of-interest (ROIs). Voxel-wise interrogation of the FPCIT PET scans revealed a single significant cluster in which DAT binding correlated with PDCP expression (p<0.05, corrected). This cluster was localized to the left caudate nucleus; an analogous correlation (r=-0.63, p<0.01) was also present in the "mirror" region of the right hemisphere. These findings were confirmed by the presence of a significant correlation (r=-0.67, p<0.005) between PDCP expression and DAT binding in caudate ROIs, which survived adjustment for age, disease duration, and clinical severity ratings. Correlation between caudate DAT binding and subject expression of the PD motor-related metabolic pattern was not significant (p>0.21). In summary, this study demonstrates a significant relationship between loss of dopaminergic input to the caudate nucleus and the expression of a cognition-related disease network in unmedicated PD patients. These baseline measures likely function in concert to determine the cognitive effects of dopaminergic therapy in PD.

Topics: Caudate Nucleus; Dopamine; Female; Fluorodeoxyglucose F18; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

A previous clinical trial studied the effect of long-term treatment with levodopa (LD) or the dopamine agonist pramipexole (PPX) on disease progression in Parkinson disease using SPECT with the dopamine transporter (DAT)-radioligand [(123)I]β-CIT as surrogate marker. [(123)I]β-CIT binding declined to significantly lower levels in patients receiving LD compared to PPX. However, the interpretation of this difference as LD-induced neurotoxicity, PPX-induced neuroprotection/-regeneration, or only drug-induced regulatory changes of DAT-availability remained controversial. To address this question experimentally, we induced a subtotal lesion of the substantia nigra in mice by bilateral injection of the neurotoxin 6-hydroxydopamine. After 4 weeks, mice were treated for 20 weeks orally with LD (100mg/kg/day) or PPX (3mg/kg/day), or water (vehicle) only. The integrity of nigrostriatal projections was assessed by repeated [(123)I]FP-CIT SPECT in vivo and by immunostaining for DAT and the dopamine-synthesizing enzyme tyrosine hydroxylase (TH) after sacrifice. In sham-lesioned mice, we found that both LD and PPX treatment significantly decreased the striatal FP-CIT binding (LD: -21%; PPX: -14%) and TH-immunoreactivity (LD: -42%; PPX: -45%), but increased DAT-immunoreactivity (LD: +42%; PPX: +33%) compared to controls without dopaminergic treatment. In 6-hydroxydopamine-lesioned mice, however, neither LD nor PPX significantly influenced the stably reduced FP-CIT SPECT signal (LD: -66%; PPX: -66%; controls -66%), TH-immunoreactivity (LD: -70%; PPX: -72%; controls: -77%) and DAT-immunoreactivity (LD: -70%; PPX: -75%; controls: -75%) in the striatum or the number of TH-positive cells in the substantia nigra (LD: -88%; PPX: -88%; controls: -86%), compared to lesioned mice without dopaminergic treatment. In conclusion, chronic dopaminergic stimulation with LD or PPX induced similar adaptive presynaptic changes in healthy mice, but no discernible changes in severely lesioned mice. These findings allow to more reliably interpret the results from clinical trials using neuroimaging of DAT as surrogate parameter.

Topics: Animals; Antiparkinson Agents; Benzothiazoles; Dopamine Agonists; Dopamine Plasma Membrane Transport Proteins; Levodopa; Longitudinal Studies; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Parkinson Disease; Pramipexole; Presynaptic Terminals; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tropanes

Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake.. Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aβ42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out.. Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake.. Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.

Topics: Aged; Biomarkers; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Primary Progressive Nonfluent Aphasia; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopamine transporter imaging with single-photon emission computed tomography (SPECT) is a valuable tool for both clinical routine and research studies. Recently, it was found that the image quality could be improved by introduction of the three-dimensional ordered subset expectation maximization (3D-OSEM) reconstruction algorithm, which provides resolution recovery. The aim of this study was to systematically evaluate the potential benefits of 3D-OSEM in comparison with 2D-OSEM under critical imaging conditions, for example, scans with a high radius of rotation.. Monte Carlo simulation scans of a digital brain phantom with various disease states and different radii of rotation ranging from 13 to 30 cm were reconstructed with both 2D-OSEM and 3D-OSEM algorithms. Specific striatal binding and putamen-to-caudate ratios were determined and compared with true values in the phantom.. The percentage recovery of true striatal binding was similar between both reconstruction algorithms at the minimum rotational radius; however, at the maximum rotational radius, it decreased from 53 to 43% for 3D-OSEM and from 52 to 26% for 2D-OSEM. 3D-OSEM matched the true putamen-to-caudate ratios more closely than did 2D-OSEM in scans with high SPECT rotation radii.. 3D-OSEM offers a promising image quality gain. It outperforms 2D-OSEM, particularly in studies with limited resolutions (such as scans acquired with a high radius of rotation) but does not improve the accuracy of the putamen-to-caudate ratios. Whether the benefits of better recovery in studies with higher radii of rotation could potentially increase the diagnostic power of dopamine transporter SPECT in patients with borderline striatal radiotracer binding, however, needs to be further examined.

Topics: Humans; Imaging, Three-Dimensional; Monte Carlo Method; Parkinson Disease; Rotation; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Aged; Brain; Dopamine; Dopamine Plasma Membrane Transport Proteins; Functional Laterality; Humans; Iodine Radioisotopes; Middle Aged; Parkinson Disease; Rest; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Orthostatic hypotension and non-dipping are relatively common autonomic dysfunctions in patients with Parkinson disease (PD). These abnormalities have been thought to occur independently of striatal dopaminergic depletion; however, only little preliminary information is available. In this study, we investigated the association of neurocirculatory changes with striatal dopamine transporter status in 69 patients with early PD. Seventeen patients had orthostatic hypotension and 55 patients were non-dippers. A comparison between cases with and without orthostatic hypotension was insignificant for striatal dopamine transporter uptake. These insignificances continued in a comparison of dippers and non-dippers. These results suggest that sympathetic noradrenergic dysfunctions in PD are independent of striatal dopamine transporter depletion.

Topics: Aged; Blood Pressure; Chi-Square Distribution; Corpus Striatum; Dopamine; Female; Head Movements; Humans; Hypotension, Orthostatic; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Tilt-Table Test; Tomography, X-Ray Computed; Tropanes

To analyse the differences in the clinical features and characteristics of (123)I-labelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) single photon emission CT (SPECT) imaging among patients with vascular parkinsonism (VP) and Parkinson's disease (PD).. We performed a case-control study to compare clinical features and qualitative and semi-quantitative analyses of (123)I-FP-CIT SPECT images between 106 patients with VP and 280 patients with PD. A case series study was used to search for clinical features related to SPECT or neuroimaging findings among patients with VP.. Patients with VP had a higher age at symptom onset and lower disease duration than patients with PD. The most frequent symptom at onset was gait disorder in VP and tremor in PD. Gait disorder, postural instability and falls were more frequent in VP. Rest and mixed tremor were more prevalent in PD. Of the patients who received levodopa treatment in the VP group, only about half had a good response. Qualitatively (123)I-FP-CIT SPECT images were normal in 32.5% of patients with VP and abnormal in all patients with PD. The use of different visual score patterns showed higher ability to differentiate VP from PD. Semi-quantitative analysis showed significantly higher uptake in the striatum, caudate and putamen in VP. The asymmetry index was higher in patients with PD. Among patients with VP, falls were the only clinical feature that demonstrated a correlation with the SPECT visual pattern.. Our data contribute to the confirmation that VP and PD are two different clinical entities. Neurological signs, response to treatment and qualitative and semi-quantitative (123)I-FP-CIT SPECT analyses may help to make the diagnosis.

Topics: Aged; Brain; Case-Control Studies; Cerebrovascular Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Functional Neuroimaging; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Cerebrovascular Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Functional Neuroimaging; Humans; Male; Parkinson Disease; Parkinson Disease, Secondary; Tropanes

To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2 G2019S mutation (AsG2019S+).. These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2 G2019S mutation (AsG2019S-), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls.. Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S- also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S- (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%.. Independently of age at examination, the most frequently altered premotor biomarker in LRRK2 G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.

Topics: Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Cohort Studies; Cross-Sectional Studies; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Glycine; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Male; Middle Aged; Mutation; Nortropanes; Olfaction Disorders; Parkinson Disease; Protein Serine-Threonine Kinases; Serine; Severity of Illness Index; Smell; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Doppler, Transcranial

Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson's disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS™ software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Leukoencephalopathies; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to investigate whether visual assessment of (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan ((123)I-FP-CIT) single photon emission computed tomography (SPECT) in addition to quantitative analyses can help to differentiate idiopathic Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). From a consecutive series of patients examined with (123)I-FP-CIT SPECT (n = 190) over a three-year period we identified 165 patients with a clinical diagnosis of PD (n = 120) or APS (n = 45). (123)I-FP-CIT SPECT results were analysed visually and quantitatively and compared for PD and APS and for the subgroup of patients with early PD and APS (disease duration <5 years). According to predefined visual patterns of dopaminergic degeneration the results were graded as normal (grade 5) or abnormal (grade 1-4), distinguishing a posterior-anterior degeneration pattern ("egg shape") from a global and severe degeneration pattern ("burst striatum"). Visual assessment of (123)I-FP-CIT SPECT showed significant different dopaminergic degeneration patterns for PD and APS patients. A grade 1 ("burst striatum") degeneration pattern was predominantly associated with APS patients. In contrast to that, a grade 2 (egg shape) degeneration pattern was the characteristic finding in PD patients. In a subgroup of patients with early disease, visual assessment with identification of the burst striatum degeneration pattern provided 90% positive predictive value and 99% specificity for the diagnosis of APS. Quantitative analysis of striatal binding ratios failed to depict these different degeneration patterns in PD and APS patients. Visual assessment of the pattern of dopaminergic loss in (123)I-FP-CIT SPECT shows different patterns of dopaminergic degeneration for PD and APS patients. Therefore, it could provide valuable information to distinguish APS from PD patients, especially in early stages of disease. Within the first 5 years of disease, the occurrence of a burst striatum degeneration pattern has a high positive predictive value of APS.

Topics: Aged; Brain; Dopaminergic Neurons; Female; Humans; Male; Middle Aged; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and (123)I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.

Topics: Aged; Diagnostic Techniques, Ophthalmological; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Pupil Disorders; Radioligand Assay; Radionuclide Imaging; Reflex, Abnormal; Tropanes

L-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinson's disease. In classical DRD no changes in the dopaminergic uptake have been observed.. A 65-year old woman presented with clinically remarkably slowly progressing Parkinson's disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [(123)I] FP-CIT-SPECT (DaTSCAN™) in order to elucidate a striatal dopaminergic deficit.. We found a reduced uptake in the [(123)I] FP-CIT-SPECT (DaTSCAN™) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene.. Patients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [(123)I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.

Topics: Aged; Antiparkinson Agents; Corpus Striatum; Dystonic Disorders; Female; GTP Cyclohydrolase; Humans; Levodopa; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results.. In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters.. No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity.. Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.

Topics: Aged; Analysis of Variance; Corpus Striatum; Echoencephalography; Female; Humans; Male; Middle Aged; Parkinson Disease; Severity of Illness Index; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes; Ultrasonography, Doppler, Transcranial

Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of (18)F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET in differentiating PSP and MSA from PD.. Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with (18)F-FP-CIT PET. The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum [VS], anterior caudate [AC], posterior caudate, anterior putamen, posterior putamen [PP], and ventral putamen [VP]) and 1 occipital VOI template. The nondisplaceable binding potential (BP(ND)) and intersubregional ratio (ISR; defined as the ratio of the BP(ND) of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated.. The BP(ND) of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P < 0.05). The BP(ND) of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BP(ND) of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (<0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (>0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively. The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD.. Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features.

Topics: Aged; Aging; Corpus Striatum; Data Interpretation, Statistical; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Positron-Emission Tomography; Predictive Value of Tests; Putamen; Radiopharmaceuticals; Supranuclear Palsy, Progressive; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon; Tropanes

Patients with Parkinson's disease (PD) have higher-order discriminative sensory dysfunction including prolonged somesthetic temporal discrimination threshold (sTDT). We studied the effect of striatal dopamine loss on the prolongation of sTDT and also studied the impact of prolonged sTDT values on the various parkinsonian motor deficits.. In 30 patients with PD, the severity of parkinsonian motor deficits was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores during levodopa off and on periods. The UPDRS motor subscores were calculated, representing bradykinesia, rigidity, tremor, and axial motor deficits. During levodopa off and on periods, the sTDT value of each index finger was studied. Using [(18) F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FPCIT) positron emission tomography studies, caudate and putaminal dopamine transporter uptake levels were measured. Multiple regression analysis covariated with age was used for statistical analysis.. During the off period, the striatal FPCIT uptake levels had an impact on the sTDT values (P < 0.01). The sTDT values had an impact on the UPDRS subscores for axial motor deficits (P < 0.05), but had no impact on those for bradykinesia, rigidity, and tremor. The sTDT values as well as UPDRS total motor scores and all UPDRS subscores were improved by a single oral levodopa treatment.. Striatal dopamine deficiency and consequent basal ganglia dysfunction may prolong sTDT, and higher-order discriminative sensory dysfunction seems to contribute in part to the development of axial motor deficits in patients with PD.

Topics: Adult; Aged; Aged, 80 and over; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensation Disorders; Touch Perception; Tropanes

The differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with (123)I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative SPECT (123)I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs.. Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals.. Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There was also a significant reduction in the tracer accumulation in the left putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET at (so many months afterwards) revealed no significant change in clinical presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of them (so many months afterwards) was negative in all but one. This one had an equivocal baseline study which deteriorated 12 months later.. Our results do not support the hypothesis of a link between essential tremor and Parkinson's disease. However, it appears that ET patients have a small degree of striatal dopaminergic degeneration. If this is due to alterations in the nigrostriatl pathway or of other origin it is not clear. Follow-up studies of essential tremor patients are warranted to assess progression of disease and to understand better the possible cause for striatal dopaminergic degeneration.

Topics: Case-Control Studies; Diagnosis, Differential; Dopamine; Essential Tremor; Female; Humans; Male; Motor Activity; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

123I-FP-CIT brain single-photon emission computed tomography (SPECT), DaTSCAN imaging, offers a possibility to study structural and biochemical integrity of presinaptic dopaminergic neurotransmitter system. The aim of this study was to evaluate the usefulness of 123I-FP-CIT brain SPECT scintigraphy in patients with extrapyramidal diseases.. Fifteen patients (8 males and 7 females), aged 26-81 years, presenting with extrapyramidal symptoms entered the study. Out of them, 7 patients were diagnosed with definite clinical form of idiopathic Parkinson's disease (PD) or clinical probable for PD clinical stage 2-4 using the Hoehn & Yahr scale (H & Y); 6 patients were with atypical parkinsonism (AP), 1 patient with essential, and 1 with psychogenic tremor. SPECT was performed 180 min after injection of 185 MBq 123I FP-CIT using a dual head Gamma camera. Sixty four one minutes' frames were acquired using a noncircular rotation mode into a 128 x 128 image matrix. Transverse slices were reconstructed using a 0.6 order Butterworth filter. Visual interpretation was based on striatal uptake, left to right asymmetry and substructures most affected. The ratio of binding for the entire striatum, caudate and putamen to nonspecific binding in occipital cortex was calculated. SPECT findings were categorized as normal and abnormal (incipient, moderate and severe presinaptic deficit).. 123I-FP-CIT uptake was reduced in the striatum of 6/7 patients with PD and 5/6 patients with AP. Two patients with PD and AP showed a negative finding. The remaining 2 negative results were obtained in the patients diagnosed with essential tremor and psychogenic tremor. The mean striato-occipital ratio (SDR) of the most affected side was lower in the patients with PD.. Our first results confirm the usefulness of 123I-FP-CIT brain SPECT in differential diagnosis of extrapyramidal diseases.

Topics: Adult; Aged; Aged, 80 and over; Brain; Carbon Radioisotopes; Essential Tremor; Female; Fluorine Radioisotopes; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (123I-FP-CIT) single photon emission computed tomography (SPECT) can be evaluated by both visual assessment and quantitative analysis to assess the striatal dopamine state in vivo. The aim of our study was to investigate if visual assessment according to a predefined image grading scale reflects the results of quantitative assessment techniques.. 195 patients with a clinical diagnosis of idiopathic Parkinson's disease (n = 134), atypical parkinsonian syndrome (n = 47) or essential tremor (n = 14) were examined with 123I-FP-CIT SPECT and included in this retrospective study. Results were analysed according to predefined visual patterns of dopaminergic degeneration and graded as normal (grade 5) or abnormal (grade 1-4) independently by three raters. Quantitative two-dimensional (2D) operator-dependent, manual and three-dimensional (3D) operator-independent, automated approaches were used for quantitative analysis of the specific 123I-FP-CIT tracer binding ratio (SBR) for caudate and putamen.. Sensitivity, specificity, PPV, NPV and diagnostic accuracy of visual assessment of 123I-FP-CIT SPECT for the diagnosis of a neurodegenerative Parkinson's syndrome were 99%, 86%, 99%, 86% and 98%, respectively. Visual assessment and quantitative analysis agreed well in evaluating the degree of dopaminergic degeneration. Significant differences (p<0.001) were found between degeneration patterns. Only between the so-called eagle wing degeneration and the normal pattern no significant differences in SBR caudate and putamen were found, neither by the quantitative manual (p = 1.00; p = 0.196) nor by the quantitative automated method (p=1.0; p = 0.785). Inter-rater agreement for visual assessment was substantial for all possible pairs of the three raters (κ = 0.70 to 0.74). Strong correlations were observed between the quantitative manual and quantitative automated methods for quantification of SBR caudatum (r = 0.920, r² = 0.846, p<0.001) and SBR putamen (r = 0.908, r²=0.824, p < 0.001).. Visual assessment was highly consistent with the results obtained by quantitative analysis and showed a substantial inter-rater agreement between experienced and inexperienced raters. Our findings indicate that visual assessment might be a reliable analysis approach for clinical routine.

Topics: Corpus Striatum; Dopaminergic Neurons; Female; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Observer Variation; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Adult; Age of Onset; Brain; Cognition; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Movement; Neuropsychological Tests; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Spinocerebellar Ataxias; Tropanes

The objective of this study was to assess striatal dopamine transporter availability in patients with advanced Parkinson's disease (PD) before and after 13 months of unilateral extradural motor cortex stimulation (EMCS) with [123I]N-ω-fluoropropyl-2-β-carbo-methoxy-3-β-(4-iodophenyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT).. Six PD patients (five women and one man, aged 63.2 ± 5.6 years) underwent 123I-FP-CIT SPECT and clinical evaluation [Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Quality of Life Scale (PDQL)] preoperatively, 8 and 13 months after EMCS. Striatum-to-occipital cortex, caudate-to-occipital cortex and putamen-to-occipital cortex 123I-FP-CIT uptake ratios were calculated using the region of interest method.. Total and part III UPDRS scores significantly decreased at 8 and 13 months after stimulation (P=0.02 and 0.04, respectively); UPDRS part II and PDQL scores improved after 13 months (P=0.02 and 0.04, respectively). No significant differences in 123I-FP-CIT uptake ratios between baseline and follow-up were found in the examined regions. However, a progressive reduction in 123I-FP-CIT uptake ratios in the striatum contralateral to the implant was found. In contrast, no further decrease in 123I-FP-CIT uptake ratios was detected in the striatum ipsilateral to the implant. There were no correlations between changes in 123I-FP-CIT uptake ratios with disease duration, changes in medication dosage and motor UPDRS scores.. Despite a small but highly selected sample of advanced PD patients, our results showed that no further dopamine transporter reduction occurred in the striatum ipsilateral to the implant side. This finding could lead to the hypothesis that EMCS might elicit a 'neuroprotective' effect, as suggested by significant clinical benefits.

Topics: Deep Brain Stimulation; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Motor Cortex; Neostriatum; Parkinson Disease; Retrospective Studies; Synaptic Transmission; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and ¹²³I-FP-CIT as the dopamine transporter ligand.. Thirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right- and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with ¹²³I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms.. Comparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate.. We reported an association between nigrostriatal DAT availability deficits and anxiety symptoms in newly diagnosed, untreated PD patients. Our results suggest that hypofunction of the nigrostriatal dopaminergic system may represent one of the functional anomalies involved in anxiety in PD from the earliest stages of disease and irrespective of any therapy.

Topics: Aged; Anxiety; Case-Control Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Follow-Up Studies; Functional Laterality; Humans; Male; Middle Aged; Parkinson Disease; Psychiatric Status Rating Scales; Regression Analysis; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of (123)I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity.. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific (123)I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects.. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and (123)I-FP-CIT uptake ratios in healthy subjects.. We found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the inverse correlation was present in each group of patients, supporting the fascinating perspective that common subcortical substrates may be involved in both anxiety and depression dimensions and movement disorders.

Topics: Adult; Aged; Behavioral Symptoms; Brain; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Dystonia; Female; Humans; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

To determine the role of striatal dopaminergic innervation on upper limb synergies during walking, we measured arm kinematics in 13 subjects with Parkinson disease. Patients were recruited according to several inclusion criteria to represent the best possible in vivo model of dopaminergic denervation. Of relevance, we included only subjects with normal spatio-temporal parameters of the stride and gait speed to avoid an impairment of upper limbs locomotor synergies as a consequence of gait impairment per se. Dopaminergic innervation of the striatum was measured by FP-CIT and SPECT. All patients showed a reduction of gait-associated arms movement. No linear correlation was found between arm ROM reduction and contralateral dopaminergic putaminal innervation loss. Still, a partition analysis revealed a 80% chance of reduced arm ROM when putaminal dopamine content loss was >47%. A significant correlation was described between the asymmetry indices of the swinging of the two arms and dopaminergic striatal innervation. When arm ROM was reduced, we found a positive correlation between upper-lower limb phase shift modulation (at different gait velocities) and striatal dopaminergic innervation. These findings are preliminary evidence that dopaminergic striatal tone plays a modulatory role in upper-limb locomotor synergies and upper-lower limb coupling while walking at different velocities.

Topics: Aged; Arm; Biomechanical Phenomena; Corpus Striatum; Dopamine; Dopaminergic Neurons; Female; Gait; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes; Walking

Topics: Humans; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

To elucidate whether Parkinson's disease subtypes show a different pattern of Iodine-123 fluoropropyl-;carbomethoxy-3 β-(FP-CIT) single photon emission computed tomography (SPECT) binding in accordance with neuropathological findings.. We analyzed a database of consecutive patients with FP-CIT scan (n = 190) over a 3-year period and identified 122 patients (50 women, 72 men, mean age 62 ± 11.1 years) with a diagnosis of idiopathic Parkinson's disease. Patient's characteristics and FP-CIT scan results were analyzed and compared for the subgroups tremor-dominant versus akinetic-rigid and equivalent type of Parkinson's disease.. The analysis of all Parkinson's disease patients showed a significant difference between the FP-CIT uptake in the subgroups tremor-dominant and akinetic-rigid. After matching these samples for age, disease duration, disease severity (Hoehn & Yahr grade, Unified Parkinson's Disease Rating Scale score), and levodopa-equivalent dose, these findings were balanced between both groups (n = 23/23) without a significant difference (P > 0.05). However, there was a clear, significant association of visually analyzed shapes of the striatum in FP-CIT SPECT and clinical Parkinson's disease subtype.. These results confirm neuropathological models for a reduced dopaminergic projection to the dorsal putamen in akinetic-rigid patients as well as the lateral putamen and caudate nucleus in tremor-dominant patients in vivo.

Topics: Aged; Brain Mapping; Corpus Striatum; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

A 58-year old woman with chronic schizophrenia developed worsening parkinsonian symptoms over the previous 6 years, and was eventually diagnosed as having Parkinson's disease. Antipsychotics were stopped because they worsened these symptoms. Antiparkinsonian treatment led to a significant increase in delusions and behavioural disorganisation. The patient underwent electroconvulsive-therapy which improved both her psychiatric and motor symptoms. After treatment, 123I-Ioflupane uptake was mildly increased in the left caudate nucleus, but uptake in right caudate nucleus was lower than in a pretreatment scan.

Topics: Caudate Nucleus; Dopamine Plasma Membrane Transport Proteins; Electroshock; Female; Humans; Middle Aged; Nortropanes; Parkinson Disease; Schizophrenia; Tomography, Emission-Computed, Single-Photon

To assess the functional state of nigro-striatal pathway using FP-CIT-I-123 in patients with clinical diagnosis of Multiple System Atrophy (MSA) subtype C.. We included 10 patients with a clinical diagnosis of MSA-C and compared them with 10 patients diagnosed with essential tremor (controls) and 10 with Parkinson Disease (PD). The studies are evaluated by the striatum/occipital index (S/O). We calculated the diagnostic validity of the procedure by ROC curve analysis.. The average value of the S/O index showed a mean of 1.48 (0.23), 1.59 (0.17) and 1.22 (0.16) respectively for MSA-C, control group (p=0.25) and PD (p=0.00). ROC curve analysis: Az: 0.650; sensitivity: 0.50; specificity: 0.80. The comparison between the results of FP-CIT and clinical manifestations showed: 4 patients with parkinsonism (PK) and pathological study; 4 without PK and normal study; 1 with PK and normal study and 1 without PK and pathological study.. FP-CIT study does not exclude completely the existence of an MSA-C. From a functional point of view, there does not always seem to be a consistency between the state of the nigro-striatal pathway and the existence of parkinsonism.

Topics: Aged; Aged, 80 and over; Carbon Radioisotopes; Cerebellum; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Fluorine Radioisotopes; Humans; Iodine Radioisotopes; Male; Middle Aged; Multiple System Atrophy; Nerve Tissue Proteins; Parkinson Disease; Parkinsonian Disorders; Radiopharmaceuticals; ROC Curve; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: 3-Iodobenzylguanidine; Aged; Disease Progression; Female; Humans; Muscular Atrophy, Spinal; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Spinal Curvatures; Tropanes

Topics: Adult; Craniocerebral Trauma; Deep Brain Stimulation; Functional Laterality; Humans; Magnetic Resonance Imaging; Male; Parkinson Disease; Subthalamic Nucleus; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes; Ventral Thalamic Nuclei

The objective of this study was to investigate whether higher levels of urate, an antioxidant linked to a lower likelihood of developing Parkinson's disease, is also a predictor of having a dopamine transporter brain scan without evidence of dopaminergic deficit. In a cross-sectional study of 797 mildly affected, untreated parkinsonian subjects diagnosed with early Parkinson's disease in the Parkinson Research Examination of CEP-1347 Trial, we investigated the relationship at baseline between serum urate and striatal dopamine transporter density, determined by single-photon emission computed tomography of iodine-123-labeled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane uptake. A scan without evidence of dopaminergic deficit was defined as lowest putamen iodine-123-labeled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane > 80% age-expected putamen dopamine transporter density. The odds of having a scan without evidence of dopaminergic deficit rose across increasing quintiles of urate level, with an age- and sex-adjusted odds ratio of 3.2 comparing the highest to the lowest urate quintile (95% confidence interval, 1.5-7.2; P for trend = .0003), and remained significant after adjusting for potential confounding factors. The association was significant in men but not women, regardless of whether common or sex-specific quintiles of urate were used. Higher levels of urate were associated with a greater likelihood of a scan without evidence of dopaminergic deficit among subjects with early untreated parkinsonism in the Parkinson Research Examination of CEP-1347 Trial. The findings support the diagnostic utility of urate in combination with other determinants.

Topics: Adult; Aged; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease; Probability; Retrospective Studies; Sex Factors; Tomography, Emission-Computed, Single-Photon; Tropanes; Uric Acid

Graft-induced dyskinesias are a serious complication after neural transplantation in Parkinson's disease. One patient with Parkinson's disease, treated with fetal grafts 14 years ago and deep brain stimulation 6 years ago, showed marked improvement of motor symptoms but continued to suffer from OFF-medication graft-induced dyskinesias. The patient received a series of clinical and imaging assessments. Positron emission tomography and single-photon emission computed tomography 14 years posttransplantation revealed an elevated serotonin/dopamine transporter ratio in the grafted striatum compatible with serotonergic hyperinnervation. Inhibition of serotonin neuron activity by systemic administration of a 5-HT(1A) agonist suppressed graft-induced dyskinesias. Our data provide further evidence that serotonergic neurons mediate graft-induced dyskinesias in Parkinson's disease. Achieving a normal striatal serotonin/dopamine transporter ratio following transplantation of fetal tissue or stem cells should be necessary to avoid the development of graft-induced dyskinesias.

Topics: Brain Mapping; Brain Tissue Transplantation; Corpus Striatum; Dihydroxyphenylalanine; Dopamine Plasma Membrane Transport Proteins; Dyskinesias; Functional Laterality; Humans; Longitudinal Studies; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Serotonin Plasma Membrane Transport Proteins; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Hyposmia is highly prevalent in the motor phase of Parkinson's disease (PD) and is an established pre-motor sign of PD that may precede the onset of motor symptoms by as long as 5 years. The data presented here are part of an ongoing study to determine the relationship of the olfactory deficit in PD with both motor and non-motor features of the disease. The study population so far includes 96 patients with a clinical diagnosis of PD (UK PD Society Brain Bank criteria; mean age 64.9 years; mean disease duration 4.8 years). Olfactory testing was performed using the 40-item UPSIT. We analyzed the relationship between UPSIT scores and measures of motor (disease duration, stage and severity) and non-motor (cognitive function, depression, anxiety and sleep) function. In 60 PD patients, [(123)I]FP-CIT SPECT scans were available to assess the relationship between UPSIT scores and striatal dopamine transporter (DAT) binding. Preliminary analyses revealed correlations of the olfactory deficit in PD with both motor and non-motor features, as well as with striatal DAT binding. These data suggest that the olfactory deficit in PD is not stationary by the time the motor phase is entered, but continues to progress over time. Hyposmia may therefore be useful as a marker of disease progression, at least in the early disease stages.

Topics: Aged; Anxiety; Cognition Disorders; Corpus Striatum; Depression; Disease Progression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Parkinson Disease; Protein Binding; Severity of Illness Index; Sleep Wake Disorders; Tomography, Emission-Computed, Single-Photon; Tropanes

Studies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. Little is known however, about the functional state of the LC in patients with Parkinson disease (PD).. We retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([¹²³I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane). FP-CIT binding values from the patients were compared with 15 healthy subjects: using both a voxel-based whole brain analysis and a volume of interest analysis of a priori defined brain regions.. Average FP-CIT binding in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p < 0.001). In contrast, subjects with PD showed an increased binding in the LC (166% on average; p < 0.001) in both analyses. LC-binding correlated negatively with striatal FP-CIT binding values (caudate: contralateral, ρ = -0.28, p < 0.01 and ipsilateral ρ = -0.26, p < 0.01; putamen: contralateral, ρ = -0.29, p < 0.01 and ipsilateral ρ = -0.29, p < 0.01).. These findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with early stage PD, compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections.

Topics: Adult; Aged; Dopamine Plasma Membrane Transport Proteins; Female; History, 17th Century; Humans; Locus Coeruleus; Male; Parkinson Disease; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

The various associations of motor and non-motor symptoms, the onset of motor complications, the cognitive disorder's appearance and other factors make Parkinson's disease (PD) a heterogeneous syndrome with multiple phenotypes. The necessity of discriminating between different forms of PD could have a role in understanding the pathophysiology of extrapyramidal signs with clinical implications. The aim of this study was to evaluate if there is a relationship between the clinical motor phenotypes of PD and the scintigraphic pattern of 123I-FP-CIT single photon emission computed tomography (SPECT). We examined 47 patients with early idiopathic PD (25 males; 22 females; mean age 58±2 years) and subdivided them in different clinical forms on the basis of dominance of resting tremor (n=20), bradykinesia plus rigidity (n=20) and the presence of both clinical signs [mixed type (MT, n=7)]. We correlated this status with the semi-quantitative analysis of SPECT with 123I-FP-CIT. Tremor type patients showed a lower reduction of 123I-FP-CIT uptake compared to akinetic-rigid type patients in contralateral caudate (P=0.0139) and putamen (P=0.0028) nuclei. 123I-FP-CIT uptake was higher in the ipsilateral caudate (P=0.0050) and putamen (P=0.0012) of tremor type patients compared to akinetic-rigid type patients. Comparisons of the striatal uptake in the tremor type and akinetic-rigid type patients with the MT patients revealed significant differences only in the ipsilateral and contralateral caudate. Our data indicate that in akinetic-rigid patients the dopaminergic system is more involved compared to that in the tremor type patients and that this difference is present from the initial stage of the disease. Moreover, our results suggest that PD phenotypes could be related not only to the dopaminergic involvement but also to other systems.

Topics: Female; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

We investigated whether dopamine influences the rate of adaptation to a visuomotor distortion and the transfer of this learning from the right to the left limb in human subjects. We thus studied patients with Parkinson disease as a putative in vivo model of dopaminergic denervation. Despite normal adaptation rates, patients showed a reduced transfer compared with age-matched healthy controls. The magnitude of the transfer, but not of the adaptation rate, was positively predicted by the values of dopamine-transporter binding of the right caudate and putamen. We conclude that striatal dopaminergic activity plays an important role in the transfer of visuomotor skills.

Topics: Adaptation, Physiological; Adult; Aged; Brain Mapping; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Extremities; Female; Humans; Male; Middle Aged; Motor Skills; Parkinson Disease; Photic Stimulation; Time Factors; Tomography, Emission-Computed, Single-Photon; Transfer, Psychology; Tropanes

The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients.. Twenty-six de novo untreated PD patients were scanned with (123)I-FP-CIT SPECT and (18)F-FDG PET. The dopaminergic impairment was measured with putaminal (123)I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP(OSEM)) and the least-squares (LS) method (BP(LS)). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc.. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP(OSEM) and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP(LS) and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison).. Putaminal BP(LS) is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

Topics: Algorithms; Brain; Dopamine; Female; Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Least-Squares Analysis; Male; Middle Aged; Motor Activity; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Tropanes

To determine clinical predictors and accuracy of (123)I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD).. Several clinical features and (123)I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated.. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively (123)I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy.. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by (123)I-FP-CIT SPECT imaging.

Topics: Aged; Cohort Studies; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

In idiopathic Parkinson's disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic-rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP-CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor.. To evaluate FP-CIT uptake in TD and ART phenotypes.. We retrospectively evaluated from our database the pre-synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset.. Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson's Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP-CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor.. These data suggest that other neurotransmitter systems apart from the nigro-striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.

Topics: Age Factors; Aged; Cohort Studies; Corpus Striatum; Databases, Factual; Female; Functional Laterality; Humans; Male; Middle Aged; Parkinson Disease; Presynaptic Terminals; Radiopharmaceuticals; Retrospective Studies; Severity of Illness Index; Substantia Nigra; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug-naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I-123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS-VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS-EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS-III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro-putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies.

Topics: Aged; Cognition Disorders; Corpus Striatum; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Neural Pathways; Neuropsychological Tests; Parkinson Disease; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

The efficacy of dopamine (DA) agonists in the treatment of motor symptoms of Parkinson's disease (PD) has been clearly demonstrated. It has also been documented that DA agonists may have both a positive and a negative impact on neuropsychiatric symptoms in PD patients. This paper will focus on the effects of DA agonists on depressive and cognitive symptoms of PD.

Topics: Aged; Clinical Trials as Topic; Cognition Disorders; Depression; Dopamine Agonists; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Psychiatric Status Rating Scales; Radionuclide Imaging; Tropanes

Pathological gambling (PG) represents a behavioral side effect of dopamine replacement therapy in a minority of patients with Parkinson's disease (PD). Using striatal dopamine transporter (DAT) with single photon emission tomography we assessed presynaptic dopaminergic function in 8 PD patients with PG, 21 matched PD control subjects, and 14 healthy subjects. Statistical Parametric Mapping was applied for image analysis. The analysis of variance (ANOVA) revealed that the three groups differed in dorsal and ventral striata bilaterally. The post-hoc analysis displayed a reduced tracer binding in the ventral striatum of PD patients with PG compared to PD controls, possibly reflecting either a reduction of mesolimbic projections or, alternatively, a lower membrane DAT expression on presynaptic terminals. The latter hypothesis is most likely given that the functional reduction of presynaptic reuptake would be more consistent with the increased dopamine levels in the ventral striatum recently reported in PD gamblers.

Topics: Aged; Basal Ganglia; Binding, Competitive; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gambling; Humans; Male; Middle Aged; Neostriatum; Parkinson Disease; Protein Binding; Tomography, Emission-Computed, Single-Photon; Tropanes

To evaluate whether dopamine transport system imaging by FP-CIT single-photon emission computed tomography (SPECT) can be helpful to differentiate idiopathic Parkinson's disease (IPD) from secondary Parkinsonism induced by amiodarone.. Twenty-two patients with Parkinsonism during amiodarone therapy were evaluated by clinical neurological examination and FP-CIT SPECT. Thereafter, amiodarone was discontinued whenever possible and antiparkinsonian treatment was modified, if required. Clinical neurological status was reevaluated within a year of the SPECT examination.. At baseline, clinical neurological examination was quite similar in all patients. No clinical symptom was able to clearly orientate the diagnosis toward IPD or drug-induced Parkinsonism. Using SPECT, the number of normal and abnormal patients was evenly distributed. In the abnormal SPECT group, amiodarone was modified in seven patients of whom six improved at follow-up. Antiparkinsonian treatment had been modified in all the patients. In the four cases with no amiodarone changes, clinical improvement was noted if antiparkinsonian treatment was optimized (three patients). In the 11 normal SPECT patients, amiodarone was modified in five patients. All patients ameliorated (two) or even normalized (three). In the six patients with normal SPECT in whom amiodarone had not been modified, symptoms remained stable despite the absence of antiparkinsonian treatment.. In patients treated with amiodarone, IPD is sometimes clinically difficult to differentiate from drug-induced Parkinsonism. Using FP-CIT, a normal scan suggests drug-induced Parkinsonism, hence, there is no need for antiparkinsonian treatment and all possible attempts to reduce or preferably stop amiodarone. An abnormal scan, on the other hand, indicates IPD. In this case, treating IPD seems to have more impact on motor changes than modifying the antiarrhythmic drug.

Topics: Aged; Amiodarone; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Parkinson Disease; Parkinsonian Disorders; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

To contribute to the differentiation of Parkinson's disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using (123)I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT).. (123)I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (H&Y) score of ≤2 (early PD), and 63 with PD with a H&Y score of ≥2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an "average performance PNN" was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated.. For PNN, the probability of correct classification in patients with early PD was 81.9±8.1% (mean±SD), in patients with advanced PD 78.9±8.1%, and in ET patients 96.6±2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5±3.4%. This means that patients with putamen values >5.99 were classified as having ET, while patients with putamen values <5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8±5.3%), and if the value was <6.97 patients were classified as having advanced PD (probability 88.1%±8.8%).. These results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities.

Topics: Adult; Aged; Aged, 80 and over; Brain; Data Interpretation, Statistical; Diagnosis, Differential; Essential Tremor; Female; Humans; Male; Middle Aged; Neural Networks, Computer; Parkinson Disease; Probability; Tomography, Emission-Computed, Single-Photon; Tropanes

To evaluate relationship between odour identification, taste threshold, dopamine transporter scan (DaTSCAN) and motor function in early Parkinson's disease (PD) and their diagnostic accuracy.. Seventy-three patients with early parkinsonism were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), DaTSCAN, electrogustometry (EGM) threshold and University of Pennsylvania Smell Identification Test (UPSIT). Olfactory Event-Related potentials (OERP) were performed on 49 patients. At follow-up (mean 15.3 months), patients were diagnosed as 'PD' or 'non-PD'. DaTSCAN images were assessed visually and semi-quantitatively by QuantiSPECT.. The sensitivity of UPSIT (86%) was not significantly different from that of the DaTSCAN (92%). UPSIT correlated moderately with DaTSCAN uptake (r = 0.44; P < 0.005) and UPDRS score (r = 0.43; P < 0.05) and weakly with symptom duration (r = 0.25; P < 0.05). In the PD group, OERP showed increased latency but no change in amplitude and no correlation with DaTSCAN. EGM thresholds were impaired in 22% of the PD group but they did not correlate with any other test parameters. DaTSCAN-UPSIT discordance was found in nine patients with PD, but neither was diagnostically superior.. Our patients with early PD have a frequent and severe olfactory deficit that correlates with disease severity, symptom duration and DaTSCAN but not EGM. The sensitivities of UPSIT and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for 'localization', UPSIT is considerably 'cheaper', and neither is disease specific. EGM threshold impairment in PD is independent of the smell deficit, and probably signifies advanced disease.

Topics: Adult; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Evoked Potentials; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Sensory Thresholds; Smell; Taste

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Topics: Aged; Aged, 80 and over; Basal Ganglia Diseases; Brain; Carbon Radioisotopes; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Gait Disorders, Neurologic; Glucose; Humans; Hypokinesia; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Mesencephalon; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Supranuclear Palsy, Progressive; Tropanes

Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls.. Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated.. FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques.. FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.

Topics: Adult; Aged; Brain; Case-Control Studies; Dihydroxyphenylalanine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Sex Characteristics; Tomography, Emission-Computed, Single-Photon; Tropanes

Depression is a common symptom in patients suffering from Parkinson's disease (PD) and markedly reduces their quality of life. As post-mortem studies have shown, its presence may reflect extensive cell loss in the midbrain and brainstem with imbalances in monoaminergic neurotransmitters. However, in vivo evidence of specific monoaminergic deficits in depressed PD patients is still sparse. Therefore, we studied PD patients with depression (PD+D) and without depression (PD-D) using high-resolution single-photon emission computed tomography (SPECT) and the monoamine transporter marker [(123)I]FP-CIT.. A magnetic resonance imaging-based region-of-interest analysis was applied to quantify the specific-to-nondisplaceable [(123)I]FP-CIT binding coefficient V(3)'' in the striatum, thalamus and midbrain/brainstem regions.. PD+D patients had significantly lower V(3)'' compared with PD-D patients in the striatum (p<0.001), thalamus (p=0.002), and midbrain/brainstem (p=0.025). Only PD+D patients without selective serotonin reuptake inhibitor (SSRI) treatment showed lower thalamic and midbrain V(3)'' than controls (p<0.001, p=0.029). In a small sub-group of SSRI-treated PD+D patients neither thalamic V(3)'' nor midbrain/brainstem V(3)'' differed from those in PD-D patients (p=0.168, p=0.201) or controls (p=0.384, p=0.318).. Our data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients. These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor symptoms in this common movement disorder.

Topics: Aged; Biogenic Monoamines; Brain; Depression; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tropanes

Previous reports showed the reduction of dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease. In this work, we sought to investigate the possible correlation between central and peripheral dopamine transporter immunoreactivity values in a group of 11 drug-naive patients with Parkinson's disease.. Densitometric measurements of dopamine transporter immunoreactivity in peripheral blood lymphocytes was accomplished as described recently, using a monoclonal antidopamine transporter antibody. Dopamine transporter binding in the caudate and putamen nuclei was measured by means of (123)I-fluopane single-photon emission computed tomography in the same patients.. The results failed to show any significant correlation between dopamine transporter immunoreactivity in peripheral blood lymphocytes and the caudate or putamen dopamine transporter binding. Moreover, dopamine transporter immunoreactivity in peripheral blood lymphocytes was reduced also in the single patient with normal striatal dopamine transporter binding.. These results indicate the lack of correlation between central and peripheral dopamine transporter reduction in Parkinson's disease, using the methodologies applied herein. They therefore suggest that the two phenomena are unlikely to share a common pathogenetic mechanism.

Topics: Adult; Aged; Caudate Nucleus; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Lymphocytes; Male; Middle Aged; Parkinson Disease; Putamen; Tomography, Emission-Computed, Single-Photon; Tropanes

The wide variability of dystonic postures manifested in the clinical course of Parkinson's disease (PD) represents a complicated on-going issue. Several recently published reports of Pisa syndrome (PS) in parkinsonian patients on dopaminergic therapy have described a variable means of onset and clinical course of this truncal dystonia.. To describe PD patients with PS, with the aim of stressing the frequent iatrogenic origin and potential reversibility of this syndrome during the initial stages of its appearance.. Eight consecutive PD patients who developed a PS after modifications of antiparkinson therapy were studied. All patients underwent detailed clinical assessment, [(123)I]FP-CIT-SPECT being performed in three cases. Four patients were videotaped.. All patients developed PS within a variable time-span ranging from 15 days to 3 months after adjustment of treatment. Seven cases of PS were manifested following an increase and one a decrease of dopaminergic treatment. A marked reversal of dystonia was produced in the first seven patients by the withdrawal or dose decrease of dopaminergic PS priming drug, and in the eighth patient an increase of dopaminergic therapy was necessary.. In our opinion, the recognition of reversibility of PS during the initial stages of its appearance may be of considerable clinical importance. Indeed, it may facilitate the rapid withdrawal or reintroduction of dopaminergic treatment, thus avoiding an initial veering towards the subchronic variant and, subsequently into a chronic irreversible variant.

Topics: Aged; Aged, 80 and over; Benserazide; Benzothiazoles; Brain; Carbidopa; Dopamine Agents; Dystonia; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Pergolide; Pramipexole; Severity of Illness Index; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to assess the ability of a single SPECT performed in the early stage of Parkinson's disease (PD) to predict disease severity in 19 patients with early PD. [(123)I]-FP-CIT striatal uptake was expressed as a ratio of specific:nonspecific uptake for defined brain areas. Clinical severity was determined by the UPDRS at baseline and 12-15 months following the SPECT procedure. [(123)I]-FP-CIT uptake in the contralateral putamen and striatum was correlated with UPDRS score at baseline, with a more significant correlation after 1-year interval. [(123)I]-FP-CIT uptake in all areas was correlated with bradykinesia and rigidity subscores only at follow up visit. Significant correlations were found between [(123)I]-FP-CIT uptake in the contralateral striatum, putamen and caudate and the difference between motor scores of 1-year interval (DeltaUPDRS). These results suggest that disease severity might be anticipated by a single SPECT at an early stage of the disease.

Topics: Adult; Aged; Dyskinesias; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscle Rigidity; Neostriatum; Neurologic Examination; Parkinson Disease; Putamen; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate the possible association between essential tremor (ET) and Parkinson's disease (PD) we conducted a prospective clinical and epidemiological study in a population of similar genetic background. The first-degree relatives of 303 PD probands and 249 controls from Crete were evaluated for the presence of ET. In addition, the possible co-occurrence of ET and PD in the same family or in the same individual was investigated. Results showed that ET was present in the relatives of PD patients more often than in those of controls (OR:3.64, P < 0.001). The risk was even greater (OR: 4.48) when the affected proband had tremor-dominant or mixed PD. Female relatives and siblings of PD patients were more likely to have ET than male relatives and parents of PD patients (OR: 4.36 v/s 2.89 and 4.49 v/s 2.74, respectively). Twelve subjects had both ET and PD phenotypes. While this may have occurred by chance, a number of families were identified in which ET and PD were coinherited through the same parental line. Hence, in certain families ET and PD are genetically related probably sharing common hereditary predisposition.

Topics: Adult; Age of Onset; Aged; Brain; Essential Tremor; Family Health; Female; Genetic Predisposition to Disease; Greece; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parents; Parkinson Disease; Pedigree; Radiopharmaceuticals; Sex Factors; Siblings; Tomography, Emission-Computed, Single-Photon

We performed 123I-FP-CIT/SPECT and ECD/SPECT in 30 patients with Parkinson's disease with dementia (PDD) and 30 patients with dementia with Lewy bodies (DLB) to evaluate whether presynaptic nigro-striatal function and/or cerebral perfusional pattern is different in these diseases. The striatal uptake of DAT tracer was statistically significantly lower in PDD and DLB with respect to control data (p < 0.0005), however no significant difference was found between PDD and DLB. Patients with PDD and DLB showed a significant reduction of rCBF (p < 0.001) in parieto-occipital and frontal areas, with respect to controls, but the comparison between the two groups did not result in any significant difference by SPM analysis. Finally no correlation was found between any regional perfusional changes and nigro-striatal dysfunction. We conclude that neither studies with 123I-FP-CIT nor ECD/SPECT were able to discriminate between DLB and PDD in vivo.

Topics: Aged; Aged, 80 and over; Brain Mapping; Cerebrovascular Circulation; Corpus Striatum; Dementia; Diterpenes, Clerodane; Female; Humans; Iodine Radioisotopes; Lewy Body Disease; Male; Parkinson Disease; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with (123)I-labeled ligand N-delta-(fluoropropyl)-2 beta-carbomethoxy-3beta-(4-iodophenyl)tropene ((123)I-FP-CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, (123)I-FP-CIT imaging was performed in 18 well-characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. The seresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB.

Topics: Aged; Caudate Nucleus; Delusions; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Hallucinations; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Male; Middle Aged; Neostriatum; Neuropsychological Tests; Nucleus Accumbens; Parkinson Disease; Psychiatric Status Rating Scales; Putamen; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

UK-based community studies have found high rates of misdiagnosis in Parkinson's disease (PD). Searches of prescription databases and case records identified 610 patients taking antiparkinson therapy for a PD diagnosis in 92 West of Scotland General Practices. Patients with no documented progression of parkinsonism and/or no increase in antiparkinson medication for 3 years were assessed by two movement disorder specialists. FP-CIT SPECT scanning was performed in clinically uncertain cases. Those considered unlikely to have PD had antiparkinson drugs tapered then stopped, with a minimum of 6 months follow-up. Age, sex and disease duration matched controls were also assessed. 64 of 89 (71.9%) patients meeting selection criteria were assessed, of whom 36 (56.3%) were appropriate for therapy withdrawal. Thirty three of those 36 patients (91.7%) and 3 of 64 (4.7%) controls stopped antiparkinson therapy without deterioration giving an overall total of 36 of 610 (5.9%). The revised diagnoses in this group were mainly essential tremor (ET) (n = 14) and vascular parkinsonism (VP) (n = 10). Patients managed in Primary Care were significantly more likely to complete therapy withdrawal than those attending a specialist clinic (15.3% vs. 2.6%, P < 0.0001). The total annual cost of antiparkinson medication for these 36 patients was 13,400 pounds; the mean duration of diagnosis was 6.8 years (SD 5.6). At least 1 in every 20 patients taking medication for PD is misdiagnosed. Nearly all of these patients can be identified by simple screening of prescription databases and case records in Primary Care, followed by clinical review, which allows withdrawal of unnecessary medication.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Essential Tremor; Female; Follow-Up Studies; Humans; Male; Parkinson Disease; Practice Patterns, Physicians'; Radiopharmaceuticals; Scotland; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Antipsychotic Agents; Cerebral Aqueduct; Constriction, Pathologic; Humans; Hydrocephalus; Injections, Subcutaneous; Levodopa; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

We studied whether the (123)I-FP-CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 +/- 12.7 years) underwent the (123)I-FP-CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and (123)I-FP-CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with (123)I-FP-CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia.

Topics: Aged; Cognition; Corpus Striatum; Depression; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Regression Analysis; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-omega-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]iodophenyl-nortropane ((123)I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease.. Thirty-six de novo PD patients underwent (123)I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal (123)I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP(FBP), BP(OSEM), BP(LS)).. The range of values of striatal BP(LS) was significantly greater than BP(FBP) and BP(OSEM). For all striatal regions, estimates of BP(FBP) correlated well with BP(OSEM) (r = 0.84) and with BP(LS) (r = 0.64); BP(OSEM) correlated significantly with BP(LS) (r = 0.76). A good correlation was found between putaminal BP(LS) and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = -0.46, r = -0.42, r = -0.39, respectively). Neither putaminal BP(FBP) nor putaminal BP(OSEM) correlated with any of these motor scores.. In de novo PD patients, (123)I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of (123)I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.

Topics: Aged; Aged, 80 and over; Corpus Striatum; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Motor Activity; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD)-the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) -is time-consuming, subjective, and has suboptimal sensitivity. A brief timed motor test (TMT) battery could possibly overcome these drawbacks. Two hundred eighty-eight PD patients (disease duration 3.1 years; preceding dopaminergic treatment initiation) were assessed with the UPDRS-III and nine TMTs based on aspects of (a) walking, (b) writing, (c) single and double-handed pegboard performance, (d) finger tapping, and (e) rapid alternating forearm movements. We investigated validity, reliability, responsiveness, and feasibility. Completing the TMT battery took less than 5 minutes. The TMT correlated well with UPDRS-III and disease duration. Two factors explained 61% of the TMT variance, the first represented mainly upper extremity function, the second mainly axial/lower extremity function. Cronbach's alpha was equal for the TMT and the UPDRS-III (0.8). Test-retest reliability of the TMT sumscore was 0.93 to 0.89 for measurements separated by 3 up to 24 months, whereas UPDRS-III correlations were 0.88 to 0.84. At group level, a trial using "change from baseline" as endpoint requires only 75% of the patients needed with the UPDRS-III when applying the TMT battery, and 57% using the pegboard dexterity test. At patient level, TMT and UPDRS-III were equally responsive. The TMT battery described here is valid, reliable, and feasible. Compared to the UPDRS-III, it is more objective and more sensitive to change. Therefore, it could be a useful tool for both practical and scientific purposes. (c) 2008 Movement Disorder Society.

Topics: Adult; Aged; Factor Analysis, Statistical; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Activity; Parkinson Disease; Psychomotor Performance; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Statistics as Topic; Task Performance and Analysis; Tomography, Emission-Computed, Single-Photon; Tropanes; Walking

Economic evaluation (Italian NHS perspective) modeling (123)I-FP-CIT SPECT (DaTSCAN) compared to clinical judgment alone for differentiating essential tremor (ET) from Parkinson's Disease (PD). A 5-year Markov model was constructed to assess the cost-effectiveness of (123)I-FP-CIT SPECT to differentiate ET from PD in patients referred to a movement disorder specialist in Italy. Published data and a double-round, Delphi panel of 12 specialists populated the model. Effectiveness was expressed as the projected Years on potentially beneficial therapy (PBTYs). Costs were expressed in Euros (2005 values). The model suggests that over 5 years, the "current" diagnostic pathway generated an average of 2.3 PBTYs/patient at an estimated cost of 8,864 euros. (123)I-FP-CIT SPECT generated an average of 4.1 PBTYs/patient at an estimated cost of 8,422 euros, which represented an additional 1.8 PBTYs at a cost saving of 442 euros/patient (341 euros when discounted at 5%). The estimated cost-effectiveness of (123)I-FP-CIT SPECT is under 1,000 euros per PBTY gained when the underlying disease prevalence is high (55-70%), and cost-saving at prevalence under 55%. (123)I-FP-CIT SPECT is likely to be regarded as economically advantageous to differentiate ET from PD, increasing time on potentially beneficial therapy at a lower overall cost to the healthcare system.

Topics: Analysis of Variance; Cost-Benefit Analysis; Diagnosis, Differential; Essential Tremor; Evaluation Studies as Topic; Humans; Italy; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

An increased echogenicity of the substantia nigra in patients with Parkinson's disease has been demonstrated by brain parenchyma sonography (BPS). BPS is a new and non-invasive technique that allows imaging of the brain in 2-dimensional axial slices. Changes in echogenicity can be displayed using ultrasounds. The aim of this study is to evaluate substantia nigra echogenicity in a group of Parkinson's disease patients and controls and compare with disease and functional neuroimaging parameters using ioflupane-single photon emission computed tomography (SPECT).. Fourty-two subjects were recruited consecutively. BPS and ioflupane-SPECT were performed in all.. Around 90% of Parkinson's disease patients showed a distinctive increase of echogenicity of substantia nigra above or equal 0.18 cm2, whereas this echo feature was detected in 11% of controls. Most of patients (86%) with an area of substantia nigra echogenicity above or equal 0.18 cm2 showed a nigro-striatal impairment, that is, a decreased ioflupane uptake measured by SPECT.. BPS is a useful tool in the diagnosis of Parkinson's disease. A good agreement between both techniques was achieved. The diagnosis accuracy obtained using BPS does not seem superior to ioflupane-SPECT. Nevertheless, hyperechogenicity could be considered as a vulnerability "marker" of the substantia nigra.

Topics: Aged; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Doppler, Transcranial

Topics: Aged; Humans; Iodine Isotopes; Male; Parkinson Disease; Psychotic Disorders; Schizophrenia; Tomography, Emission-Computed, Single-Photon; Tropanes

Pisa syndrome (PS) is a dystonic lateroflexion of the trunk with a postural disturbance resembling the leaning tower of Pisa. Initially reported as a side effect related to antipsychotic therapy, this original dystonic posture is also manifested in neurodegenerative disorders such as Alzheimer's disease and multiple system atrophy, or in rare idiopathic cases. Recent observations have described the onset of PS with subchronic course in patients affected by Parkinson's disease (PD). Here, we report on the acute development of PS in a parkinsonian patient during treatment with entacapone/levodopa/carbidopa combination. This case illustrates how, in contrast to previously well-known chronic/subchronic forms, this axial dystonic posture may occur in PD as an acute onset reversible type, related to levodopa treatment.

Topics: Antiparkinson Agents; Carbidopa; Catechols; Dystonic Disorders; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The concept of vascular parkinsonism (VP) has evolved since it was introduced by Critchley. The relationships between the clinical manifestations and neuroimagining of patients with VP to determine the utility of SPECT in its diagnosis have been established.. Retrospective study of patients with suspicion of VP according to Ziljmans 2004 criteria.. A total of 22 patients were included. The most frequent risk factor was AHT. The most frequent manifestations were: bradykinesis, followed by gait disorder. Response to L-dopa was related with symptoms in lower limbs (p=0.014). The most frequent alterations on the magnetic resonance imaging were: atrophy with ventricular dilation followed by white matter lesions. The Hachinski scale was related with acute onset (p=0.022) and territorial infarction (p=0.039), and the Winikates with subcortical- paraventricular white matter lesions (p=0.036), and both with gender (male) (p=0.031), and stroke background (p=0.022). Alteration in gait was associated with paraventricular white matter lesions (p = 0.043), and other manifestations with lesions in the medulla (p=0,020). Tremor was associated with bilateral involvement of putamens in SPECT (p=0.039), strategic lesion with putamen involvement (p = 0.028) and lesions of periventricular white matter lesions with SPECT type 1 and 2 (p=0.045). There were no significant relationships of the SPECT with response to L-dopa or with the scales. Discussion. The different relationships between symptoms, scales and neuroimagin show the complexity of the subject and the need to use all of them in the diagnosis of VP.

Topics: Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Nortropanes; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Vascular Diseases

The quality of visually and semi-quantitatively assessed DaTSCAN images is crucial for differential diagnostics of extrapyramidal diseases. Neuroimaging with the use of presynaptic tracers of the dopaminergic system provides evidence of nigrostriatal degeneration and may support the clinical diagnosis of Parkinsonism. During the last two years (2007-2008) we tried to elaborate the optimal methodology of SPECT/CT examination with the use of DaTSCAN ((123)I-Ioflupane), and we sought to evaluate the effect of the reconstruction and attenuation correction method on semi-quantitative measures of relative uptake in the striatum. In a present study, we retrospectively studied DaTSCAN scans of 44 consecutive patients with clinical indications of Parkinson's disease or uncertain Parkinsonian syndromes. The quality of DaTSCAN images reconstructed with the use of ordered-subset expectation maximization reconstruction technique (OSEM) with attenuation correction based on CT maps was found to be superior to that provided by the commonly applied filtered backprojection method (FBP) with Chang attenuation correction. OSEM reconstructed transverse slices were more legible for clinical interpretation because of increased contrast and improved delineation between striatum structures. Semi-quantitative assessments of relative striatum uptake for OSEM reconstructed slices secured better intra-operator reproducibility than that obtained by FBP method.

Topics: Adult; Aged; Aged, 80 and over; Artifacts; Basal Ganglia Diseases; Essential Tremor; Female; Humans; Image Enhancement; Male; Middle Aged; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

alpha-Synuclein gene (SNCA) multiplication was found in familial Parkinson disease (PD). We examined SNCA multiplication in patients with familial and sporadic PD and multiple system atrophy (MSA).. We screened 1,106 patients with parkinsonism (PD = 906, MSA = 200) for SNCA multiplication by multiplex PCR. Fluorescent in situ hybridization was done to confirm the multiplication. [(123)I]N-omega-Fluoropropyl-2 beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]FP-CIT) SPECT was done in the patients with SNCA multiplication and their family members.. Three patients were identified as having SNCA duplication. One patient had a positive family history, and two patients were sporadic. Each patient had asymptomatic carriers in their families. The familial case had early onset parkinsonism with rapidly progressive course, cognitive impairment, and dysautonomia. Sporadic cases were more typical of PD. [(123)I]FP-CIT SPECT was abnormal in the patients and normal in the asymptomatic carriers.. SNCA multiplication is present in sporadic Parkinson disease (PD) and needs to be screened. Low penetrance, clinical heterogeneity, and normal dopamine transporter imaging in asymptomatic carriers may suggest the presence of other genetic modifiers or environmental triggers that play a role in the pathogenesis of PD due to SNCA duplication.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Synuclein; Child; DNA Mutational Analysis; Exons; Family Health; Female; Humans; In Situ Hybridization, Fluorescence; Iodine Radioisotopes; Male; Middle Aged; Multiple System Atrophy; Mutation; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

We aimed to investigate the accuracy of transcranial brain parenchyma sonography (TCS) for differentiation between idiopathic Parkinson's disease (PD) and essential tremor (ET) in comparison to (123)I-FP-CIT SPECT (FP-CIT SPECT). Seventy-four patients, in whom PD or ET was suspected on the basis of clinical criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP-CIT SPECT, respectively. Three patients were excluded due to an insufficient transtemporal bone window using TCS. Forty-six and 25 patients were clinically classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71 included patients. Thirty-six of the 42 patients with abnormal FP-CIT SPECT findings had a pathological SN hyperechogenicity, whereas TCS findings in the remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings the SN echogenicity was regular. Referring to FP-CIT SPECT, the sensitivity and specificity of TCS for detection of PD were 86 and 93%; the positive and negative predictive values were 95 and 82%, respectively. Sensitivity and specificity in detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and 100% for FP-CIT SPECT, respectively. In patients with pathological FP-CIT SPECT and pathological TCS, the extent of SN hyperechogenicity did not correlate with the degree of reduction in dopamine transporter binding on the side opposite of the more affected limb. TCS allows a reliable differentiation of PD and ET. The TCS SN hyperechogenicity does not correlate with the extent of dopaminergic neuron degeneration.

Topics: Aged; Brain; Essential Tremor; Female; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes; Ultrasonography

Mixed-type tremors pose a clinical diagnostic challenge. The aim of the study was to better characterize patients with combined postural and rest tremor. Patients were categorized into four groups: essential tremor (ET) (n = 7), combined rest + postural tremor (n = 17), PD (n = 17), and control subjects (n = 9). All underwent the University of Pennsylvania Smell Identification Test (UPSIT). The mixed-tremor group was also evaluated with SPECT imaging using the dopamine transporter (DaT) ligand (123)I-labeled FP-CIT. There was no significant difference in olfaction scores between the mixed tremor and essential tremor groups (23.2 +/- 6.6 vs 21.7 +/- 4.9) or between these groups and controls (27.2 +/- 5.0). The patients with PD had significantly lower scores than all the other groups (13.7 +/- 5.4, p < 0.001). Of the 12 patients with mixed tremor evaluated by SPECT, 9 had normal findings. This study suggests that rest tremor is part of the spectrum of ET, even in patients with long-standing disease. However, in a minority of patients, there might be transformation of ET-PD.

Topics: Diagnosis, Differential; Diagnostic Tests, Routine; Essential Tremor; Humans; Middle Aged; Parkinson Disease; Radiopharmaceuticals; Smell; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Dual-head SPECT systems are used by many clinical departments for [(123)I]FP-CIT SPECT imaging, while triple-head or brain-dedicated systems with better imaging performance are more commonly used by research institutions. There are limited data comparing the capability of the two types of system to measure dopamine transporter (DAT) loss in vivo.. The aim of this study was to compare the ability of a dual-head and a brain-dedicated SPECT system to estimate the degree of DAT loss in different movement disorders with variable nigrostriatal impairment, with [(123)I]FP-CIT.. Four patients with essential tremor, 24 with Parkinson's disease (PD), six with spinocerebellar ataxia type 2 and six controls were studied with [(123)I]FP-CIT. SPECT scans were performed on a dual-head (E.CAM-Siemens) and subsequently on a brain-dedicated system (Ceraspect-DSI).. Striatal DAT outcome measures on the E.CAM and the Ceraspect were strongly correlated and the putamen-to-caudate ratios were almost identical. Although the measured values were lower by 52+/-25% in caudate and by 51+/-31% in putamen on the E.CAM (p<0.0001), the average striatal DAT decrease in each patient group compared with controls was similar for both systems. In PD patients, similar correlations (p<0.05) were found between motor UPDRS or Hoehn and Yahr stage and striatal DAT density.. Despite underestimation of striatal DAT outcome measures, the E.CAM showed similar capability as the Ceraspect in measuring the degree of nigrostriatal dopaminergic deficit and assessing the correlation between DAT outcome measures and clinical variables of PD severity and stage.

Topics: Adult; Aged; Brain; Case-Control Studies; Caudate Nucleus; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Movement Disorders; Parkinson Disease; Putamen; Radiopharmaceuticals; Spinocerebellar Ataxias; Tomography, Emission-Computed, Single-Photon; Tropanes

We used (123)I-Ioflupane SPECT to study 32 unrelated patients with essential tremor (16 with positive familial history), 47 sporadic tremor dominant patients with Parkinson's disease and 31 healthy control subjects. Discriminant analysis was used to categorize healthy subjects and patients with Parkinson's disease or essential tremor.. Patients with essential tremor had higher uptake values (50% putamen and 21% caudate, P<0.001) compared to those with Parkinson's disease but lower than healthy subjects (15% putamen and 21% caudate, P<0.05). Discriminant analysis classified seven essential tremor patients in the healthy subjects cohort (22%) and two as Parkinson's disease (6%).. Our results show that some essential tremor patients may present mild abnormalities of striatal dopamine transporters and a typical Parkinson's disease-like pattern of uptake loss. These findings suggest a link between the two disorders.

Topics: Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Image Interpretation, Computer-Assisted; Iodine Radioisotopes; Male; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I-123]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p<0.01). Contralateral putamen and caudate nucleus FP-CIT uptake correlated significantly with severity of rigidity (p<0.01) and hypokinesia (p<0.01) but not with severity of resting or postural tremor (p>0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor.

Topics: Adult; Age of Onset; Aged; Binding, Competitive; Caudate Nucleus; Corpus Striatum; Diagnosis, Differential; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Muscle Rigidity; Occipital Lobe; Parkinson Disease; Predictive Value of Tests; Putamen; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Striatal postsynaptic D2 receptors in Parkinson's disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D2 binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool.. Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of < or = 5 years and 26 age-matched controls. Striatal D2 binding was assessed with [123I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [123I]FP-CIT SPECT.. The mean striato-occipital ratio of [123I]IBZM binding was significantly higher in PD patients (1.56 +/-0.09) than in controls (1.53 +/-0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 +/-0.09 vs 1.55 +/-0.10 ipsilaterally), suggesting D2 receptor upregulation, and the reverse was seen using [123I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation.. Our study confirms asymmetric D2 receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [123I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D2 receptors, assessed with [123I]IBZM SPECT.

Topics: Benzamides; Biomarkers; Corpus Striatum; Female; Humans; Male; Middle Aged; Parkinson Disease; Pyrrolidines; Radiography; Radiopharmaceuticals; Receptors, Dopamine D2; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes; Up-Regulation

We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa-responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa-responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation.

Topics: Ataxins; Family Health; Female; Humans; Italy; Magnetic Resonance Imaging; Male; Mutation; Nerve Tissue Proteins; Parkinson Disease; Radionuclide Imaging; Trinucleotide Repeat Expansion; Tropanes

Challenge with low-dose apomorphine causes a rise in growth hormone (GH) in patients with Parkinson's disease (PD). We studied 18 patients with early PD, who showed an increase of GH in the low-dose apomorphine test, by means of [(123)I] FP-CIT-SPECT. The mean specific dopamine transporter binding of the 18 patients was 1.50 +/- 0.56 in the striatum, 1.20 +/- 0.59 in the putamen, and 1.76 +/- 0.59 in the caudate nucleus. The increase of GH (1.05 +/- 1.01 ng/ml at baseline to 9.46 +/- 6.36 ng/ml 45 min after apomorphine injection; p < 0.001) was significant. There was a significant negative correlation of the increase of GH with the mean specific dopamine transporter binding in all three regions (r between -0.490 and -0.587; p between 0.04 and 0.01). Challenge with low-dose apomorphine may therefore be used as an indirect tool to measure the extent of nigrostriatal neurodegeneration in early PD.

Topics: Adult; Aged; Apomorphine; Binding, Competitive; Corpus Striatum; Dopamine; Dopamine Agonists; Dopamine Plasma Membrane Transport Proteins; Female; Growth Hormone; Humans; Male; Middle Aged; Parkinson Disease; Predictive Value of Tests; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

To determine diagnostic accuracy of FP-CIT SPECT in a subgroup of patients who clinically present nonconclusive or atypical characteristics of parkinsonism (Clinically Uncertain Parkinsonian Syndromes, CUPS), and assess the contribution of the quantitative analysis in this group of patients.. We included 54 patients who make up the CUPS group. After a variable follow-up period, we evaluated the existence of a degenerative parkinsonism and compared it with the result of the FP-CIT SPECT, establishing the diagnostic accuracy of this procedure in the CUPS patient group.. We obtained a high diagnostic accuracy of neurodegenerative Parkinsonism in the CUPS patient group (sensitivity: 85%; specificity: 93%). False positive results were obtained in patients with vascular parkinsonism and most of the false negative results in patients with Parkinson's disease. The quantitative evaluation did not contribute data of relevance to the qualitative evaluation.. FP-CIT SPECT makes it possible to show the involvement of nigrostriatal dopaminergic pathway, also contributing with information of relevance to the clinician about the etiology of the extrapyramidal symptomatology in patients with nonconclusive signs and symptoms of the existence of a Parkinsonism.

Topics: Adult; Aged; Aged, 80 and over; Brain; Female; Humans; Male; Middle Aged; Parkinson Disease; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate the usefulness of 18F-FP-CIT PET for assessing the severity of Parkinson's disease (PD) at various clinical stages, 41 patients with PD were divided into early (Hoehn&Yahr I-II, n = 23) and advanced (Hoehn & Yahr III-IV, n = 18) subgroups. 18F-FP-CIT PET was performed in these patients and 12 normal subjects. 18F-FP-CIT uptake in striatal subregions and its correlation with UPDRS were first evaluated by ROI analysis, and between-group differences were also analyzed by Statistical Parametric Mapping (SPM). Our results showed that striatal 18F-FP-CIT binding were significantly reduced to 70.9% (caudate), 46.8% (anterior putamen) and 24.0% (posterior putamen) in early PD compared with that of the control, and to 52.0%, 34.5% and 16.5% correspondingly in advanced PD, respectively. There was significant negative correlation between total motor UPDRS score of all parkinsonian patients and 18F-FP-CIT uptake in caudate nucleus (r = -0.53, p < 0.001), anterior putamen (r = -0.53, p < 0.001) and posterior putamen (r = -0.61, p < 0.001). SPM comparison of 18F-FP-CIT uptake between early or advanced PD and the control group showed significant decline in striatum, predominantly localized on the contralateral side and in the dorsal-posterior putamen. These results indicate that 18F-FP-CIT PET can serve as a suitable biomarker to represent the severity of PD in early and advanced stages.

Topics: Aged; Brain Mapping; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Putamen; Severity of Illness Index; Tropanes; Ultrasonography

Many patients with Parkinson's disease (PD) report daytime sleepiness. Its etiology, however, is still not fully understood. The aim of this study was to examine if the amount of nigrostriatal dopaminergic degeneration is associated with subjective daytime sleepiness in patients with PD.. We investigated 21 patients with PD clinically and by means of [(123)I] FP-CIT-SPECT (DaTSCAN(R)). Each patient filled in the Epworth sleepiness scale (ESS), the Parkinson's Disease Sleep Scale (PDSS), and the self-rating depression scale according to Zung (SDS) to assess sleepiness, sleep quality, and depressive symptoms.. The mean specific dopamine transporter binding in the 21 PD patients (60.8 +/- 10.4 years, nine females, median Hoehn and Yahr stage 2.0) was decreased. Nine patients were in Hoehn and Yahr stage 1 (58.7 +/- 6.6 years, four females; ESS score 7.4 +/- 4.5; PDSS score 105.1 +/- 30.9), the other 12 patients were in Hoehn and Yahr stage 2 (62.4 +/- 12.6 years, five females; ESS score 6.7 +/- 4.7, PDSS score 97.1 +/- 25.6). Age, gender, ESS, and PDSS scores were not significantly different in both groups. However, ESS scores showed an inverse correlation with mean DAT binding in the striatum (r = -0.627, p = 0.03), the caudate nucleus (r = -0.708, p = 0.01), and the putamen (r = -0.599, p = 0.04) in patients with Hoehn and Yahr stage 2. There was no correlation of the ESS score with age, disease duration, UPDRS motor score, PDSS score, or depression score.. Subjective daytime sleepiness seems to be associated with dopaminergic nigrostriatal degeneration in early PD.

Topics: Aged; Corpus Striatum; Disorders of Excessive Somnolence; Dopamine; Female; Humans; Male; Middle Aged; Parkinson Disease; Severity of Illness Index; Statistics, Nonparametric; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

We used 123I-Ioflupane SPECT to study striatal dopamine transporter (DAT) binding in 36 Parkinson's disease (PD) patients with history of severe occupational exposure to hydrocarbons. Data were compared with 38 PD patients without exposure history as well as healthy controls. Both PD cohorts showed significant striatal uptake decrements compared with controls. We found significantly lower values in the whole striatum of exposed compared with non-exposed patients (0.83 +/- 0.25 vs. 1.05 +/- 0.39; P = 0.004), more pronounced in the putamen (0.61 +/- 0.24 vs. 0.85 +/- 0.42; P = 0.004). We conclude that severe occupational exposure to hydrocarbons may modify disease course and ultimately accelerate nigro-striatal denervation.

Topics: Aged; Binding, Competitive; Corpus Striatum; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Hydrocarbons; Male; Middle Aged; Nerve Degeneration; Nortropanes; Occupational Exposure; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

The objective of this study was to determine whether dopamine transporter (DAT) scintigraphy influences the management of movement disorders in clinically indeterminate cases.. Seventeen patients (ten women, seven men; age range 44-84 years) with a presumptive diagnosis of Parkinson's disease (PD) were referred for single-photon emission computed tomography (SPECT) scintigraphy using [(123)I]ioflupane between November 2002 and August 2003. The scintigraphic results, clinical diagnosis, and management intentions pre- and post-examination were recorded.. Of the 17 patients who underwent scintigraphy, two patients on neuroleptic medication exhibited features of PD; one had an abnormal scintigraphic examination that confirmed PD, the other had a negative examination, confirming drug-induced parkinsonism, and these were managed accordingly. Of the other cases, the results of 10 examinations were compatible with PD. Five were reported as being normal, the final diagnoses in this group included: cerebrovascular disease (CVD); early Alzheimer's; provisional clinical diagnosis of generalized movement disorder; and possible Wilson's disease. One patient was felt to have a parkinsonian syndrome despite the normal result (this patient had a positive apomorphine test).. This series illustrates the value of DAT scintigraphy in the management of clinically indeterminate movement disorders at a tertiary referral centre arguing for its use in the initial diagnostic process. However, it is clear that the use of DAT scintigraphy poses significant resource implications. Further evidence should clarify the exact role of DAT scintigraphy in clinically indeterminate cases.

Topics: Adult; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Nortropanes; Parkinson Disease; Parkinson Disease, Secondary; Radionuclide Imaging; Retrospective Studies

There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [(123)I] FP-CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre-synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre-synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [(123)I] FP-CIT scans. Mean [(123)I] FP-CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP-CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre-synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP-CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Corpus Striatum; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Parkinson Disease, Secondary; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

(123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) is a SPECT dopamine transporter (DAT) tracer that probes dopaminergic cell loss in Parkinson's disease (PD). Quantification of (123)I-FP-CIT images is performed at equilibrium using a ratio (BR) of specific (striatal) to nonspecific (occipital) uptake with values obtained from regions of interest drawn manually over these structures. Statistical parametric mapping (SPM) is a fully automated voxel-based statistical approach that has great potential in the context of DAT imaging. However, the accuracy of the spatial normalization provided by SPM has not been validated for (123)I-FP-CIT images. Our first aim was to create an (123)I-FP-CIT template that does not require the acquisition of patient-specific MRI and to validate the spatial normalization procedure. Next, we hypothesized that this customized template could be used by different SPECT centers without affecting the outcomes of imaging analyses.. The spatial normalization to the customized template created with SPM (template A1) was validated using (123)I-FP-CIT images obtained from 6 subjects with essential tremor (ET) with normal DAT status and 6 PD patients. Variability in BR values due to the normalization was evaluated using striatal volume of interest (VOI). To determine whether different SPECT centers could use a unique (123)I-FP-CIT template, we generated 3 other (123)I-FP-CIT templates using different subjects and image-processing schemes. The interchangeability of these templates was assessed using (a) putamen BR values analyzed with the intraclass correlation coefficient (ICC) and the Bland-Altman graphical analysis, and (b) SPM analysis comparing the results of group comparisons-that is, ET versus PD, obtained after normalization to each of the 4 templates.. There was no significant difference between pre- and post-normalization striatal BR values in our study. The mean variability calculated with putamen VOI values after normalization to each template was <10%, with the lowest ICC of 98%. Intergroup analyses performed with VOI and SPM approaches provided similar results independently of the template used.. SPM normalization was accurate even in subjects with low striatal (123)I-FP-CIT uptake, making it a promising approach for automatic analysis of (123)I-FP-CIT images using a single customized template at different centers.

Topics: Aged; Brain; Data Interpretation, Statistical; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Pilot Projects; Radionuclide Imaging; Radiopharmaceuticals; Tropanes

We performed [123I]FP-CIT/SPECT in 20 drug-naive Parkinson's disease (PD) patients, 10 with unilateral akinesia/rigidity at onset (arPD) and 10 with additional tremor-at-rest (tPD), to evaluate whether resting tremor at onset is associated with differences in striatal dopamine transporter binding. Patients of the two cohorts were matched for age, disease duration (<3 years) and severity of non-tremor motor symptoms; 31 healthy participants served as controls. Mean striatal dopamine transporter binding reduction in PD patients vs. controls was 42% for arPD and 50% for tPD; mean ipsilateral striatum and caudate nucleus uptake values were lower by 12 and 24%, respectively, in tPD than arPD. We conclude that widespread degeneration of the nigrostriatal dopaminergic pathway might be necessary for the development of parkinsonian tremor-at-rest.

Topics: Aged; Corpus Striatum; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.

Topics: Animals; Cell Count; Disease Models, Animal; Dopamine; Male; Mice; Mice, Inbred C57BL; Neurons; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system.. Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage).. Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r = 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r = 0.84, both p < 0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (rho = -0.52 for both techniques), UPDRS-III (rho = -0.38 for F-DOPA; rho = -0.45 for FP-CIT) and disease duration (rho = -0.59 for F-DOPA; rho = -0.49 for FP-CIT, all p < 0.05).. FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.

Topics: Adult; Aged; Dihydroxyphenylalanine; Dopa Decarboxylase; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Male; Membrane Transport Proteins; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinsonism in patients taking neuroleptic medications might be induced by dopamine receptor blockade alone or by dopamine blockade with nigrostriatal dysfunction. The differentiation between Parkinson's disease (PD) and drug-induced parkinsonism (DIP) is difficult to assess on clinical grounds alone. In this study, we have evaluated the clinical characteristics and striatal binding of (123)I-FP-CIT (N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-{4-iodophenyl}tropane) in patients who developed DIP. A total of 20 patients (mean age, 62 +/- 13 years) who developed parkinsonism while on neuroleptic agents and 10 age-matched controls were enrolled. [123]-FP-CIT single-photon emission computed tomography (SPECT) was performed in all subjects. Neurological assessment was performed with the Motor part of the Unified Parkinson's Disease Rating Scale. [123]-FP-CIT binding of the entire striatum, caudate, and putamen was calculated. Patients were divided into two subgroups according to SPECT results for comparison of clinical characteristics. There were 9 patients who had normal scans and 11 who showed significantly diminished striatal binding, suggesting degeneration of the nigrostriatal system. Subanalyses of abnormal scans revealed significantly diminished binding in the caudate (P < 0.001 for right and left caudate) and putamen (P = 0.002 and P < 0.05 for right and left putamen, respectively). There were no differences in clinical features between patients with normal and abnormal scans. Symptoms included asymmetric tremor, bradykinesia, and rigidity in both groups. Freezing gait was present in two patients with normal scans. These results indicate that DIP is clinically indistinguishable from PD. Brain imaging with FP-CIT helps to determine whether DIP is entirely drug-induced or an exacerbation of subclinical PD.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Parkinsonian Disorders; Severity of Illness Index; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET).. One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique.. Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV).. Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.

Topics: Algorithms; Brain; Cysteine; Diagnosis, Differential; Discriminant Analysis; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Organotechnetium Compounds; Parkinson Disease; Pattern Recognition, Automated; Perfusion; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

Hyperechogenic signal of substantia nigra (SN) in transcranial sonography (TCS) and reduced striatal uptake in FP-CIT SPECT are common findings in idiopathic Parkinson's disease (PD). But so far it is unknown whether the extent of SN hyperechogenicity represents a correlate for the degeneration of presynaptic dopaminergic neurons in PD. We performed TCS and 123I-labelled N-(3-fluoropropyl)-2ss-carbomethoxy-3ss-(4-iodophenyl)nortropane ([123I]FP-CIT) SPECT in 53 patients with PD. Striatal FP-CIT uptake was quantified by measuring the striatal/posterior lobe binding of [123I]FP-CIT. SN echogenicity was quantified by planimetric measurement of the maximum extension of hyperechogenic signals. We found no correlation between striatal FP-CIT uptake and echogenicity of the SN, neither contralateral to the clinically more affected body side (r = +0.08, P = 0.57; Pearson's correlation) nor ipsilateral (r = +0.01; P = 0.92). Our data show that the extent of SN hyperechogenicity does not correlate with the degeneration of presynaptic dopaminergic nerve terminals. Obviously SN hyperechogenicity and degeneration of presynaptic dopaminergic nerve terminals exist independently from each other and may be based on different pathomechanisms.

Topics: Adult; Aged; Corpus Striatum; Echoencephalography; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Presynaptic Terminals; Severity of Illness Index; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

In the semi-quantitative assessment of DaTSCAN images, it has been suggested that the ratio of tracer accumulation in the putamen to that in the caudate nucleus may be helpful and could allow parkinsonian syndromes progression to be assessed. Separation of ratio values has been reported when early Parkinson's disease is compared with essential tremor. The separation is lost, however, when the Parkinson's disease is not early stage.. To evaluate whether a two-stage analysis can differentiate between parkinsonian syndromes, of various stages, and essential tremor, and whether such a two-stage analysis can be undertaken in a single step using artificial neural networks (ANNs).. Data from 18 patients were analysed. Quantification was undertaken by manually drawing irregular regions of interest (ROIs): over each caudate nucleus and putamen and over an occipital cortex area near the posterior edge of the brain. A two-stage analysis was undertaken and was repeated, in a single step, using an ANN.. The first stage, of the two-stage analysis, identified 12 patients with non-early parkinsonian syndromes. The remaining six patients were then successfully classified into early parkinsonian syndromes and essential tremor. The ANN analysis successfully discriminated parkinsonian syndromes from essential tremor, in all patients, in a single step.. The two-stage process provides a method for classifying early disease without being compromised by the noise from non-early disease. The results of the single stage ANN analysis were very definite and it may be considered to have potential in the quantification of DaTSCAN images for clinical use.

Topics: Adult; Aged; Aged, 80 and over; Cluster Analysis; Diagnosis, Differential; Essential Tremor; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neural Networks, Computer; Parkinson Disease; Pattern Recognition, Automated; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Syndrome; Tomography, Emission-Computed, Single-Photon; Tropanes

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage

Topics: Adult; Aged; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Narcolepsy; Nerve Tissue Proteins; Olfaction Disorders; Parkinson Disease; Polysomnography; REM Sleep Behavior Disorder; Sensory Thresholds; Sleep Apnea, Obstructive; Tomography, Emission-Computed, Single-Photon; Tropanes

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.

Topics: 3-Iodobenzylguanidine; Adult; Age Factors; Aged; Brain; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Radionuclide Imaging; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism (VP) has been addressed by only few studies up to now. Most previous reports suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in four patients with VP, reported here, the combined DAT and D2 receptor SPECT showed highly unusual changes in the pre- and/or postsynaptic dopaminergic system. The possible value of combined DAT/D2 receptor SPECT imaging should be investigated by future prospective studies.

Topics: Aged; Aged, 80 and over; Benzamides; Carbon Radioisotopes; Cerebrovascular Circulation; Dementia, Vascular; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Parkinson Disease; Pyrrolidines; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon; Tropanes

A G309D mutation in the PINK1 gene in a consanguineous Spanish kindred with seven siblings, three of whom are clinically affected, has recently been shown to be a cause of the PARK6 form of autosomal-recessive Parkinson's syndrome. In this family, we studied pre- and postsynaptic dopaminergic function using 123I-FP-CIT- and 123I-iodobenzamide-SPECT to determine binding to the presynaptic dopamine transporter (DAT) and postsynaptic D2 receptors respectively. All three PARK6 patients showed reduced striatal DAT binding with posterior preponderance similar to sporadic idiopathic PD, but only one patient showed significant striatal asymmetry. In two of the siblings, DAT binding was markedly increased. IBZM-SPECT was normal in both patients and sibs. Our findings indicate that 123I-FP-CIT-SPECT shows similar DAT binding in PARK6 patients compared to idiopathic Parkinson's disease. The increased DAT binding in heterozygous PARK6 carriers may be a new very early preclinical finding, but its significance is still unclear.

Topics: Adult; Benzamides; Carbon Radioisotopes; Corpus Striatum; Dopamine; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Family Health; Female; Genes, Recessive; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Protein Kinases; Pyrrolidines; Siblings; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

123I-FP-CIT SPECT has been successfully used to detect the loss of dopaminergic nigrostriatal neurons in Parkinson's disease at an early stage. In this study we evaluated the capacity of 123I-FP-CIT SPECT to assess bilateral dopamine transporter (DAT) loss in de-novo hemi-Parkinson's disease (PD) patients with one-sided clinical symptoms.. Twenty-nine de-novo hemi-PD patients at an early stage (Hoehn & Yahr stage 1) and 18 gender and age matched healthy subjects were studied. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (P(put)/O), and the putamen to caudate nucleus index (P(put)/C) were calculated in both the basal ganglia.. In PD patients S/O, C/O and P(put)/O ratio values contralateral to the clinically affected side were significantly lower (P<0.001) than in the control group (-38%, -34% and -42%, respectively). A significant reduction (P<0.001) of the striatal binding ratios was also found ipsilaterally (S/O, -31%; C/O, -28%; P(put)/O, -33%). The P(put)/C index was also bilaterally significantly reduced (P<0.01). DAT loss was significantly greater (P<0.001) in the contralateral than in the ipsilateral S; and putamen bilaterally presented a higher dopaminergic deficit than did caudate.. Our results indicate that semi-quantitative 123I-FP-CIT SPECT detects a bilateral dopaminergic deficit in early PD with unilateral symptoms and preclinical DAT loss in the ipsilateral striatal binding, corresponding to the side not yet affected by motor signs. Semi-quantitative analysis may thus be used to diagnose PD at an early stage as well as to identify individuals developing bilateral dopaminergic damage.

Topics: Adult; Aged; Brain; Carbon Radioisotopes; Case-Control Studies; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Neurons; Parkinson Disease; Putamen; Radionuclide Imaging; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Topics: Clinical Trials as Topic; Diagnosis, Differential; Humans; Parkinson Disease; Predictive Value of Tests; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

Patients with Parkinson's disease (PD) often have lower urinary tract symptoms (LUTS). Studies have indicated a correlation between dopaminergic degeneration and LUTS and presence of overactive bladder. We evaluated 18 patients with Parkinson's disease using single-photon emission computerized tomography (SPECT) imaging of the dopamine transporter with [(123)I]-FP-CIT, and bladder symptoms were assessed using questionnaires and full urodynamic evaluation both in medicated state and after cessation. Bladder symptoms correlated with age, stage and severity of disease but not with uptake of the ligand in the striatum. Patients with bladder symptoms had a significant lower uptake in the striatum compared with patients without LUTS. In patients with severe bladder dysfunction, LUTS correlated with putamen/caudate ratio. The specific binding of the ligand did not correlate with urodynamics parameters or any change in these after wash-out. Our findings suggest that the presence of LUTS is associated with the degeneration of the total number of nigrostriatal dopaminergic neurones, whilst the severity of bladder dysfunction is correlated with the relative degeneration of the caudate nucleus. The effects of medication on bladder control, as evaluated by urodynamics are believed to involve structures outside the basal ganglia.

Topics: Adult; Corpus Striatum; Dopamine; Female; Humans; Male; Middle Aged; Parkinson Disease; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Tropanes; Urinary Bladder, Neurogenic; Urodynamics

In general, striatal dopamine transporter (DAT) binding is assessed by use of data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate whether the use of an iterative reconstruction algorithm (ordered-subset expectation maximization [OSEM]) may provide results comparable to or even better than those obtained by standard FBP.. In 50 patients with parkinsonian syndromes, SPECT scans were acquired 4 h after injection of 185 MBq of (123)I-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) by use of a triple-head gamma-camera fitted with low-energy, high-resolution fanbeam collimators. After reconstruction by FBP and OSEM, data were filtered with a Butterworth filter and corrected for attenuation. Patient studies were automatically fitted to a mean template with a corresponding 3-dimensional (3D) volume-of-interest map covering the striatum, caudate, and putamen as well as an occipital reference region to calculate specific DAT binding. In addition, studies with an anthropomorphic 3D striatal phantom were performed to mimic different pathologies.. Visual assessment of phantom and patient data suggested a better separation between the caudate and the putamen in studies reconstructed by OSEM than in those reconstructed by FBP. There was an excellent correlation between specific DAT binding assessed by OSEM and that assessed by FBP (R(2) values: striatum, 0.999; caudate, 0.998; putamen, 0.998). Mean specific striatal binding obtained by OSEM was approximately 6% lower than that obtained by FBP. In no case was diagnostic information from OSEM inferior to that from FBP.. Iterative reconstruction of (123)I-FP-CIT SPECT studies for the assessment of DAT is feasible in routine clinical practice. A close correlation between FBP and OSEM data suggested that the latter also allow reliable quantification of DAT binding. Because of a better separation between the caudate and the putamen in the visual evaluation, as suggested by phantom and patient studies, OSEM may even be considered the preferable approach.

Topics: Adult; Aged; Algorithms; Brain; Dopamine Plasma Membrane Transport Proteins; Humans; Image Enhancement; Iodine Radioisotopes; Middle Aged; Numerical Analysis, Computer-Assisted; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Signal Processing, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tropanes

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.

Topics: Aged; Atrophy; Biomarkers; Brain; Brain Mapping; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Fragile X Syndrome; Genetic Predisposition to Disease; Heterozygote; Humans; Male; Middle Aged; Mutation; Neural Pathways; Parkinson Disease; Substantia Nigra; Synaptic Transmission; Syndrome; Tomography, Emission-Computed, Single-Photon; Tropanes

Degeneration of substantia nigra has been described in spinocerebellar ataxia type 2 (SCA2). In this study, dopamine transporter (DAT) density with [123 I]FP-CIT SPECT was studied in six SCA2 patients with no parkinsonian signs, six Parkinson's disease (PD) patients, and six controls. Marked striatal DAT loss was found in both SCA2 and PD patients. However, a more severe reduction in the caudate and a higher putamen to caudate ratio distinguished SCA2 from PD patients, suggesting a more uniform nigrostriatal impairment in SCA2. Striatal DAT density of SCA2 patients correlated with the severity of cerebellar ataxia.

Topics: Adult; Binding Sites; Case-Control Studies; Corpus Striatum; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Spinocerebellar Ataxias; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinsonism is a group of neurological disorders characterized by extrapiramidal signs. Often, the differential diagnosis between parkinsonism, essential tremor and drug-induced parkinsonism is difficult. The aim of the study was to evaluate the utility of (123I)-FP-CIT SPECT in patients with movement disorders.. 52 patients were referred from the neurology department to characterize those with parkinsonism. Patients were clinically evaluated and those with Parkinson's disease were assessed using the rating scale Hoehn & Yahr and the UPDRS motor score. Subsequently, a (123I)-FP-CIT SPECT was performed with a qualitative analysis.. All patients with essential tremor and drug-induced parkinsonism had a normal SPECT. All patients with parkinsonism displayed SPECT defects, except for four who had a normal SPECT result. Two of them were categorized as vascular parkinsonisms, one patient had a Shy-Drager's syndrome and the another one had probably a Parkinson's disease. The sensitivity and specificity were 90.47% (38/42; CI95%, 81.59%-99.35%) and 100% (10/10; CI95%, 69.15%-100%), respectively.. (123I)-FP-CIT SPECT is an effective tool to study the integrity of the dopaminergic nigrostriatal system. Moreover, it permits to characterize the different types of parkinsonism.

Topics: Aged; Basal Ganglia; Brain; Carrier Proteins; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

In this study, we tested the hypotheses that (1) the acquisition of sequential information is related to the integrity of dopaminergic input to the caudate nucleus; and (2) the integrity of dopaminergic input to the caudate nucleus correlates significantly with brain activation during sequence acquisition. Twelve early stage Parkinson's disease (PD) patients and six age-matched healthy volunteers were scanned using a dual tracer PET imaging design. All subjects were scanned with [(18)F]fluoropropyl-betaCIT (FPCIT) to measure striatal dopamine transporter (DAT) binding and with [(15)O]water to assess activation during a sequence learning task where movements were made to a repeating sequence of eight targets. Caudate and putamen DAT binding in the PD cohort was reduced by 15% and 43%, respectively. In PD, caudate DAT binding correlated with target acquisition (R = 0.57, P < 0.05), while putamen DAT binding did not correlate with performance. In volunteers, caudate DAT binding correlated with learning-related activation (P < 0.05, corrected for multiple comparisons) in the left dorsolateral and ventral prefrontal cortices, the anterior cingulate and premotor regions, and the right cerebellum. A significant correlation with caudate DAT binding was additionally detected in the right anteromedial thalamus, extending into the rostral midbrain. By contrast, in the PD cohort, most of these regional relationships were lost: Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic tone. Our findings suggest that sequence learning is normally associated with tight coupling between dopaminergic input to the caudate and thalamo-cortical functional activity. Despite minimal reductions in nigro-caudate input, PD patients demonstrate a loss of this coupling early in the disease.

Topics: Aged; Arousal; Brain Mapping; Caudate Nucleus; Cerebellum; Corpus Striatum; Dominance, Cerebral; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Fluorine Radioisotopes; Humans; Image Interpretation, Computer-Assisted; Kinesthesis; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Net; Nerve Tissue Proteins; Parkinson Disease; Prefrontal Cortex; Psychomotor Performance; Putamen; Serial Learning; Thalamus; Tomography, Emission-Computed; Tropanes

To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD.. A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived.. The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001).. This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Topics: Caudate Nucleus; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Functional Laterality; Humans; Lewy Body Disease; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Neurologic Examination; Occipital Lobe; Parkinson Disease; Psychiatric Status Rating Scales; Putamen; Severity of Illness Index; Striatonigral Degeneration; Tomography, Emission-Computed, Single-Photon; Tropanes

Dementia with Lewy bodies (DLB) is a common form of late-life dementia that can be difficult to differentiate from other disorders, especially Alzheimer disease (AD), during life. At autopsy the striatal dopaminergic transporter is reduced.. To examine the extent and pattern of dopamine transporter loss using iodine I 123-radiolabeled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) with single-photon emission computed tomography (SPECT) in DLBs compared with other dementias and to assess its potential to enhance a differential diagnosis.. Cohort study comparing FP-CIT with criterion standard of consensus clinical diagnosis.. General hospital.. One hundred sixty-four older subjects (33 healthy older control subjects, 34 with NINCDS/ADRDA [National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association]-confirmed AD, 23 with consensus guideline-confirmed DLB, 38 with United Kingdom's Parkinson Disease Society Brain Bank-confirmed Parkinson disease [PD], and 36 with PD and dementia).. Injection of (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane with SPECT scan performed at 4 hours.. Visual ratings of scans and region of interest analysis.. Significant reductions (P<.001) in FP-CIT binding occurred in the caudate and anterior and posterior putamens in subjects with DLB compared with subjects with AD and controls. Transporter loss in DLBs was of similar magnitude to that seen in PD, but with a flatter rostrocaudal (caudate-putamen) gradient (P =.001), while the greatest loss in all 3 areas was seen in those who had PD and dementia. Both region of interest analysis and visual ratings provided good separation between DLBs and AD (region of interest: sensitivity, 78%; specificity, 94%; positive predictive value, 90%) but not among subjects with DLB, PD, and PD with dementia.. Dopamine transporter loss can be detected in vivo using FP-CIT SPECT in DLB. Further studies, especially of subjects with DLB without PD, are required to fully establish use in clinical practice.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cohort Studies; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Lewy Body Disease; Male; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Essential tremor (ET) is often an alternative diagnosis to Parkinson's disease (PD) and some ET patients may later develop PD. Unlike the former, PD patients have deficient visuo-motor coordination (VMC). Recently, we have attempted to exploit this difference in order to detect PD in ambiguous neurological cases.. To assess the possibility of using VMC testing for screening ET patients prior to [123I]-FP-CIT SPECT imaging.. Ten clinically diagnosed ET patients who showed deficient VMC were subjected to [123I-FP-CIT] SPECT imaging. We expected these patients to show subnormal striatal ligand uptake, as in PD.. We found decreased [123I]-FP-CIT uptake in 80% of the patients. A significant correlation between ligand uptake and VMC was observed.. Impaired VMC is a pertinent indication for further SPECT imaging in patients with ET, in order to establish a diagnosis of incipient PD.

Topics: Aged; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Early Diagnosis; Essential Tremor; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Psychomotor Performance; Tomography, Emission-Computed, Single-Photon; Tropanes

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.

Topics: Adult; Antiparkinson Agents; Benzamides; Brain; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Levodopa; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Parkinson Disease; Phenylketonurias; Pyrrolidines; Radiopharmaceuticals; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon; Tropanes

Here we report our experience in a general hospital setting using [(123)I]-FP-CIT SPECT to diagnose patients with suspect Parkinson's disease (PD).. Thirty consecutive patients (19M, 11W, mean age: 61+/-13 years) were prospectively studied. Patients underwent MRI (27) at 1.5T or CT (3) when MRI was contraindicated, to rule out focal brain abnormalities. Motor and cognitive function were evaluated by neurologists with UPDRS and Hoehn e Yahr Scale. [(123)I]-FP-CIT striatal uptake, assessed with SPECT, was classified as normal, non-diagnostic, abnormal (unilateral or bilateral). Imaging results (SPECT+MRI) were correlated with the neurological findings.. In 5 patients the [(123)I]-FP-CIT brain SPECT was normal, suggesting that their symptoms could be related to a benign disorder such as essential tremor. Two patients had non-diagnostic [(123)I]-FP-CIT brain SPECT, with MRI/CT findings compatible with subcortical cerebrovascular disease. In the remaining 23 patients abnormal striatal [(123)I]-FP-CIT uptake correlated with neurological findings, significantly increasing the probability of Parkinson's disease. In these patients MRI/CT scans were normal, or showed a mild BA, or mild cerebral vascular disease (mild CVD).. Our results suggest that [(123)I]-FP-CIT scan could be used routinely in clinical practice to support the diagnosis of PD and to differentiate between other conditions. Moreover, FP-CIT could significantly impact treatment selection and follow-up of these patients.

Topics: Aged; Brain; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Neurologic Examination; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

To record prospectively, from early presentation, the clinical features of parkinsonism and tremor disorders, in relation to evidence of dopaminergic deficit shown with [(123)I]-FP-CIT (DaTSCAN, Amersham Health) single photon emission computerised tomography (SPECT). Clinical signs were recorded in 62 patients, of whom 24 failed standard Parkinson's disease (PD) and essential tremor criteria, and 38 fulfilled UK Brain Bank step 1 PD criteria. Striatal radioligand uptake was graded visually as normal or abnormal, and specific:nonspecific ratios were calculated. Bradykinesia and rigidity showed significant overall association with abnormal scans (P < or = 0.003), but rest tremor did not (P = NS). In the 24 patients not fulfilling specific criteria (mean age 63 [SD 9] years, disease duration 3 [SD 4] years), 10 (42%) had abnormal visual SPECT assessment and 14 (58%) had normal scans. Of 38 patients with early PD by clinical criteria (mean age 60 [SD 9] years, disease duration 3 [SD 1.7] years), 33 (87%) were visually abnormal. Baseline clinical diagnosis corresponded with SPECT imaging results in 51 of 62 cases (82%), which increased to 56 of 62 cases (90%) with amendment of seven clinical diagnoses at 3 months (blind to SPECT results). Akinetic-rigid cardinal diagnostic features of parkinsonism associate well with dopaminergic deficit in patients with early and mild clinical features. When these clinical features are uncertain, or the patient fails clinical diagnostic criteria, testing for dopaminergic deficit with [(123)I]-FP-CIT SPECT may assist the diagnostic process.

Topics: Adult; Aged; Aged, 80 and over; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Iodine Isotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Nortropanes; Parkinson Disease; Radiography; Severity of Illness Index; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Topics: Aged; Case-Control Studies; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Multiple System Atrophy; Nerve Tissue Proteins; Parkinson Disease; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes

We have shown that fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane ([(18)F]FPCIT) and PET offer a valuable means of quantifying regional abnormality in dopamine transporter (DAT) imaging associated with Parkinson's disease (PD). The objective of this study was to delineate the topographic distribution of DAT binding in early stage idiopathic PD using statistical parametric analysis of [(18)F]FPCIT PET data. We performed dynamic PET studies in 15 hemi-parkinsonian (Hoehn & Yahr I) patients and 10 age-matched normal volunteers over 100 min and calculated images of [(18)F]FPCIT binding ratios on a pixel-by-pixel basis. Statistical parametric mapping (SPM) was then used to localize binding reductions in PD and to compute the absolute change relative to normal. [(18)F]FPCIT binding decreased significantly in the contralateral posterior putamen of the PD group (P < 0.001, corrected). A significant reduction was also seen in the ipsilateral putamen, which was smaller in extent but localized more posteriorly. A quantitative comparison of DAT binding in the two clusters showed that the onset of motor symptoms in PD was associated with an approximate 70% loss relative to the normal mean in the contralateral posterior putamen. These results suggest that SPM analysis of [(18)F]FPCIT PET data can be used to quantify and map abnormalities in DAT activity within the human striatum. This method provides a useful tool to track the onset and progression of PD at its earliest stages.

Topics: Aged; Brain Mapping; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed; Tropanes

Isolated foot dystonia following exercise is a rare manifestation of early PD. It may precede the onset of parkinsonism by years and can be clinically indistinguishable from familial exercise-induced dystonia. The authors present a patient with dystonic claudication where dopamine transporter SPECT using (123)I-FP-CIT allowed early diagnosis of PD and enabled effective symptomatic treatment with a dopamine agonist.

Topics: Adult; Dopamine Plasma Membrane Transport Proteins; Dystonia; Electromyography; Exercise; Humans; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Membrane Transport Proteins; Muscular Diseases; Nerve Tissue Proteins; Neurologic Examination; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease (PD) is characterized neuropathologically by degeneration of the nigrostriatal dopaminergic pathway. With natural aging there is loss of dopaminergic cells in the substantia nigra and, consequently, loss of dopamine transporters in the striatum. It has been suggested that PD is caused by an accelerated rate of cell death. Conceptually, symptoms in idiopathic PD become apparent after a critical level of cell loss, the "symptom threshold." It has been suggested that this symptom threshold is independent of age. In this study, [123I]FP-CIT SPECT was used to assess the effect of aging on the density of striatal dopamine transporters in vivo in controls (n = 36) and early, drug-naive, patients with PD (n = 32). We found a significant age-associated decline of [123I]FP-CIT binding to striatal dopamine transporters in controls, but not in parkinsonian patients. This finding might give further support for the existence of an age-independent threshold in PD. In a subgroup of patients with hemi-PD, we found a significant loss of dopamine transporters bilaterally in the caudate nucleus and putamen. This loss was more pronounced in the putamen than in the caudate nucleus and the contralateral binding was significantly lower than the ipsilateral binding. By using age-corrected data, we estimated that in our particular patient group motor signs started when the loss of [123I]FP-CIT binding ratios in the putamen was 46-64%.

Topics: Adult; Age Factors; Aged; Aging; Carrier Proteins; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Neostriatum; Nerve Degeneration; Nerve Tissue Proteins; Neural Pathways; Neurons; Parkinson Disease; Sex Factors; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43-73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Topics: Adult; Aged; Binding Sites; Binding, Competitive; Disease Progression; Dopamine; Female; Humans; Male; Middle Aged; Neostriatum; Neural Pathways; Neuroprotective Agents; Parkinson Disease; Presynaptic Terminals; Radionuclide Imaging; Substantia Nigra; Tropanes

To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET).. [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken.. The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection.. Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Topics: Adult; Aged; Aged, 80 and over; Corpus Striatum; Diagnosis, Differential; Dominance, Cerebral; Essential Tremor; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Observer Variation; Parkinson Disease; Reference Values; Tomography, Emission-Computed, Single-Photon; Tropanes

2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop-1-en -3-yl) nortropane (IACFT) is a highly selective ligand for dopamine transporter (DAT) sites in the striatum. Recent reports have described the basic kinetics, neurobiology, and imaging properties of [123I]IACFT. This report focuses on the structural (i.e., the ability to produce consistent binding estimates) validity of 4 methods to quantify striatal binding potential (BP) for IACFT.. Seven healthy volunteers and 8 patients with Parkinson's disease were subjects for this study. Dynamic SPECT images and arterial blood samples were acquired during the 1.5-2 h after injection of 185-370 MBq [123I]IACFT. Plasma radioactivity was analyzed chromatographically to obtain metabolite-corrected arterial input functions. The k3/k4 ratio (BP) for striatal DAT sites was calculated by 4 methods. In the first method, tissue time-activity curves and metabolite-corrected arterial input functions were analyzed by a linear graphic method developed for reversible receptor ligands. The second method was also graphic; however, the occipital cortex time-activity curve was used as the input function. In the third method, the difference between the striatal and occipital cortex time-activity curves at secular equilibrium was taken to represent bound tracer, the occipital cortex time-activity curve was used to represent tracer in the free and nonspecifically bound state, and equilibrium receptor equations were used to determine BP. The fourth method used the occipital cortex time-activity curve to mathematically derive an input function for fitting the striatal time-activity curve and to determine BP.. Analysis of the dynamic SPECT data by methods 1 and 2 resulted in highly linear plots (after approximately 15 min), supporting the reversibility of the tracer. A high linear correlation was found for BP determined by all 4 methods. ANOVA showed that methods 1-3 were indistinguishable; method 4 yielded lower BPs than did methods 1-3.. These results show that BP can be estimated consistently using 4 different methods. This finding lends support to the modeling assumptions and provides methods suitable for clinical investigation.

Topics: Adult; Aged; Brain; Carrier Proteins; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Occipital Lobe; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

The variability in clinical features and the masking effects of drug therapy in Parkinson's disease (PD) can affect clinical assessment of disease severity. The aim of this study was to assess the imaging of dopamine transporters using 123I-FP-CIT SPECT and its correlation with disease staging, severity, and duration. Differences between the clinical severity of the onset and non-onset side and the corresponding striatal uptake ratios were also examined. Forty-one patients with PD (nine unilateral, 32 bilateral clinical features) were studied. Clinical severity was determined by using the Unified Parkinson's Disease Rating Score (UPDRS). Unilateral UPDRS was calculated from unilateral arm and leg resting and action tremor, rigidity, finger taps, hand movements, alternating movements, and leg agility. 123I-FP-CIT striatal uptake was expressed as the ratio of specific:nonspecific (SP:NS) uptake for defined brain areas. Patients with PD who had unilateral symptoms showed a significant difference between the ipsilateral and contralateral SP:NS ratios in both the caudate and putamen, but there was a considerable overlap between between the two sides. This result was repeated in patients with bilateral symptoms and there was overlap of SP:NS ratios between the two groups. For the whole group of patients with PD, striatum, caudate, and putamen SP:NS ratios correlated with disease severity assessed by UPDRS and duration of disease. The SP:NS ratios correlated with the bradykinesia subscore but not with rigidity or tremor subscore. In conclusion, this study provides further evidence that the SP:NS ratio is a robust measure of disease severity correlating with duration of PD. However, variability in uptake values suggest that factors other than nigrostriatal degeneration may contribute to disease severity. Correlation with bradykinesia but not with tremor may indicate an origin for tremor outwith the dopamine transporter system. 123I-FP-CIT SPECT offers significant potential in defining the nigrostriatal changes in PD.

Topics: Aged; Brain Mapping; Carrier Proteins; Corpus Striatum; Dominance, Cerebral; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Nortropanes; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Tropanes

Parkinson's disease is characterized by degeneration of dopaminergic neurons, resulting in loss of dopamine transporters in the striatum. Recently, the tracer 1231-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane (FPCIT) was developed for imaging dopamine transporters with SPECT. The purpose of this study was to develop an [123I]FPCIT SPECT protocol for routine clinical studies.. We examined the time course of [123I]FPCIT binding to dopamine transporters in 10 healthy volunteers and 19 patients with Parkinson's disease.. We found that the time of peak specific striatal [123I]FPCIT binding was highly varied among subjects, but specific binding peaked in all controls and patients within 3 h postinjection. Between 3 and 6 h, the ratio of specific-to-nonspecific striatal [123I]FPCIT binding was stable in both groups, although, as expected, it was significantly lower in patients. In the patients, [123I]FPCIT binding in the putamen was lower than in the caudate nucleus, and contralateral striatal binding was significantly lower than ipsilateral striatal binding. The subgroup of patients with hemi-Parkinson's disease showed loss of striatal dopamine transporters, even on the ipsilateral side.. For routine clinical [123I]FPCIT SPECT studies, we recommend imaging at a single time point, between 3 and 6 h postinjection, and using a tissue ratio as the outcome measure. The [123I]FPCIT SPECT technique is sensitive enough to distinguish control subjects from patients with Parkinson's disease, even at an early stage of the disease.

Topics: Brain; Carrier Proteins; Case-Control Studies; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

In SPECT, the binding of radiotracers in brain areas is usually assessed by manual positioning of regions of interest (ROIs). The disadvantages of this method are that it is an observer-dependent procedure and that it may not be sensitive for assessing defects significantly smaller than the ROI. To circumvent these limitations, we developed a fully automatic three-dimensional technique that quantifies neuronal radiotracer binding on a voxel-by-voxel basis.. To build a model of normal 123I-labeled N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane (FPCIT) binding, 17 studies of healthy volunteers were registered to the same orientation. After registration, the specific-to-nonspecific binding ratio was calculated for each voxel of the striatal volumes of interest (VOIs). The mean and SD of that binding ratio were then calculated on a voxel-by-voxel basis. For the analysis of 10 healthy volunteer studies (control group) and 21 studies of drug-naive patients with Parkinson's disease, the registration and calculation of the specific-to-nonspecific [123I]FPCIT binding ratio were performed by the same method. Subsequently, a voxel of the striata was classified as a diminished [123I]FPCIT binding ratio if its value was lower than the mean -2 x SD. For each subject, the defect size, the relative number of voxels with a diminished binding ratio and the binding ratio of the whole striatal VOIs were calculated and compared with the binding ratio as assessed by the traditional ROI method.. The results of the automatic method correlated significantly with the results of the traditional ROI method. Furthermore, for the ipsilateral side, the automatically calculated defect size had less overlap between the patient and the control group than the traditionally calculated binding ratio.. The method presented quantifies [123I]FPCIT binding ratio automatically on a voxel-by-voxel basis, by comparison with a model of healthy volunteers. We have shown that it is appropriate to use the automatic method as a replacement for the traditional manual method, which enables us to study the localized dopaminergic degeneration process in Parkinson's disease more precisely and without any inter- or intraobserver variability.

Topics: Algorithms; Carrier Proteins; Case-Control Studies; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Models, Biological; Nerve Tissue Proteins; Nortropanes; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tropanes

The aims of this study were to investigate whether the loss of striatal dopamine transporters in early and drug-naive patients with Parkinson's disease could be demonstrated by means of 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)tropane (123I-FP-CIT) SPECT in a 1-day protocol and whether the SPECT measures were correlated with disease severity.. Twenty-one early-stage and drug-naive Parkinson's disease patients (age range 42-73 yr; mean age 55.5 yr) and 14 healthy controls (age range 28-83 yr; mean age 53.6 yr) were examined. SPECT image acquisition was always performed at 3 hr postinjection. The ratio of specific to nonspecific striatal 123I-FP-CIT binding was used as the outcome measure.. All striatal 123I-FP-CIT ratios were significantly lower in the Parkinson's disease group compared to those in the control group. The mean reduction in the putamen was 57% of the control mean, and that in the caudate nucleus was 29% of the control mean. Patients with unilateral Parkinson's disease showed a bilateral loss of striatal 123I-FP-CIT binding. Discriminant function analysis, using the 123I-FP-CIT SPECT data of the ipsilateral and contralateral putamen, predicted group membership in all cases; the contralateral putamen accounted for the greatest difference between the Parkinson's disease patients and the controls. In the control group, a clear decline in 123I-FP-CIT binding was found with aging, amounting to 9.6%/decade. Unexpectedly, in the Parkinson's disease group, regression analysis revealed that neither severity of disease nor age accounted for a significant part of the variance in striatal SPECT measures.. Our findings indicate that 123I-FP-CIT SPECT is a reliable method to discriminate between early, drug-naive Parkinson's disease patients and healthy controls and to identify patients in the preclinical phase of Parkinson's disease. Possibly due to the relatively homogeneous group of Parkinson's disease patients and the use of a suboptimal outcome measure, no significant correlations were found between striatal 123I-FP-CIT binding ratios and disease severity, such as were established earlier with 123I-beta-CIT. Further research is necessary to interpret these findings.

Topics: Adult; Aged; Aged, 80 and over; Aging; Carrier Proteins; Case-Control Studies; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Regression Analysis; Severity of Illness Index; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Iodine-123-beta-carbomethoxy-3 beta-(4-iodophenyltropane) (CIT) has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. This tracer has a protracted period of striatal uptake enabling imaging 14-24 hr postinjection for stable quantitative measures of dopamine transporters, and it binds with nanomolar affinity to the serotonin transporter. Iodine-123 fluoropropyl (FP)CIT is an analog of [123I]-beta-CIT and has been shown to achieve peak tracer uptake in the brain within hours postinjection and to provide greater selectivity for the dopamine transporter. The purpose of the present study was to compare [123I]-beta-CIT with [123I]-FPCIT in a within-subject design.. Six Parkinson's disease patients and five healthy control subjects participated in one [123I]-beta-CIT and one [123I]-FPCIT SPECT scan separated by 7-21 days. Controls were imaged at 24 hr postinjection 222 MBq (6 mCi) [123I]-beta-CIT and serially from 1-6 hr postinjection 333 MBq (9 mCi) [123I]-FPCIT. Two imaging outcome measures were evaluated: (a) the ratio of specific striatal activity to nondisplaceable uptake, also designated V"3, at each imaging time point; and (b) the rate of striatal washout of radiotracer expressed as a percent reduction per hr for [123I]-FPCIT. In addition, venous plasma was obtained from the five control subjects after the [123I]-FPCIT injection for analysis of radiometabolites.. Both [123I]-FPCIT and [123I]-beta-CIT demonstrated decreased striatal uptake in Parkinson's disease patients compared with the controls with a mean of V"3=3.5 and 6.7 for [123I]-beta-CIT (Parkinson's disease and controls, respectively) and a mean of V"3=1.34 and 3.70 for [123I]-FPCIT (Parkinson's disease and controls, respectively). For [123I]-beta-CIT, the mean Parkinson's disease values represented 52% of the control uptake, while the mean [123I]-FPCIT value for Parkinson's disease patients was 37% of the control values. Analysis of [123I]-FPCIT time-activity curves for specific striatal counts showed washout rates of 8.2%/hr for Parkinson's disease and 4.9%/hr for controls.. These data suggest that SPECT imaging with [123I]-FPCIT visually demonstrates reductions in striatal uptake similar to [123I]-beta-CIT. iodine-123-FPCIT washed out from striatal tissue 15-20 times faster than [123I]-beta-CIT, and estimates of dopamine transporter loss in Parkinson's disease patients were higher for [123I]-FPCIT than for [123I]-beta-CIT. This was most likely due to the faster rate of striatal washout and establishment of transient equilibrium binding conditions at the dopamine transporter, which the modeling theory suggests produces an overestimation of dopamine transporter density with relatively greater overestimates in healthy control subjects by [123I]-FPCIT.

Topics: Aged; Carrier Proteins; Case-Control Studies; Cocaine; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Parkinson Disease; Time Factors; Tomography, Emission-Computed, Single-Photon; Tropanes

Fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FPCIT) has been synthesized as a dopamine transporter ligand for PET studies. We evaluated the regional brain uptake and the plasma metabolism of [18F]-FPCIT.. PET studies were conducted on 7 normal subjects and on 10 patients with Parkinson's disease. After the [18F]-FPCIT injection (4.4+/-1.8 mCi), dynamic scans were acquired over 100 min. Plasma metabolite analysis was performed using high-performance liquid chromatography (HPLC).. Plasma HPLC revealed two peaks corresponding to unmetabolized [18F]-FPCIT and a polar metabolite. The fraction of the parent compound decreased rapidly to 25% at 25 min. Fluorine-18-FPCIT showed a striatum-to-occipital ratio (SOR) of 3.5 at 90 min postinjection. The ratio of striatal-to-occipital distribution volume (DVR) was calculated directly by using a mean tissue-to-plasma efflux constant for occipital cortex obtained in 10 subjects (ki=0.037 min(-1)). DVR measures determined with and without plasma input function were correlated (r=0.98, p < 0.0001). In normal subjects, a significant age-related decline of DVR was observed both for caudate and putamen, corresponding to a 7.7% and 6.4% decline per decade, respectively (r > 0.85, p < 0.01). Both DVR and SOR correctly classified early-stage Parkinson's disease patients with comparable accuracy (p < 0.0001). Age-corrected DVR values correlated negatively with the Uniform Parkinson's Disease Rating Scale composite motor ratings (r=0.66, p < 0.05).. The tracer characteristics are compatible with a high-affinity, reversible ligand. FPCIT/PET demonstrated age-related decline in dopamine transporter binding in normal subjects as well as significant reductions in patients with idiopathic Parkinson's disease, which correlates with the disease severity.

Topics: Aged; Aging; Brain; Carrier Proteins; Case-Control Studies; Chromatography, High Pressure Liquid; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Fluorine Radioisotopes; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed; Tropanes

Several SPECT studies reported decreased striatal 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane ([123I]FP-CIT) binding in patients with Parkinson's disease. For application in routine clinical studies, information on the reliability and reproducibility of the [123I]FP-CIT SPECT technique is critical. This study reports on the reliability and reproducibility of [I23I]FP-CIT SPECT in healthy control subjects and patients with Parkinson's disease using two different analysis protocols: the conventional region of interest (ROI) protocol and a newly developed, fully automatic, operator-independent volume of interest (VOI) protocol.. We performed repeated [123I]FP-CIT SPECT scans in 6 healthy control subjects and 10 patients with Parkinson's disease to measure scan-to-scan variations. Scintigraphic data were analyzed 3 hr after injection of the radiotracer.. In controls, the mean test/retest for the ratio of the striatal-to-nonspecific [123I]FP-CIT uptake were (3.79 +/- 0.67/3.82 +/- 0.74) and (4.16 +/- 0.70/4.08 +/- 0.97) for the ROI and VOI technique, respectively. No significant differences were measured between test/retest studies. The mean test/retest variability for the ROI technique was low (7.25%) with excellent reliability (rho = 0.99). In addition, the mean test/retest variability for the VOI technique was also low (7.47%) with very high reliability (rho = 0.95). In Parkinson's disease patients, we found mean test/retest for the striatal-to-nonspecific [123I]FP-CIT ratio of (1.78 +/- 0.23/1.79 +/- 0.25) and (1.83 +/- 0.31/1.85 +/- 0.35) using the ROI and VOI technique, respectively. Also in patients, these results did not differ significantly between test/retest studies. The mean test/retest variability for the ROI technique was low (7.90%) with excellent reliability (rho = 1.00). In addition, the mean test/retest variability for the VOI technique was also low (7.36%) with high reliability (rho = 0.96).. Reliable and reproducible results were obtained with the ROI, as well as the VOI technique, for the analysis of striatal dopamine transporters with [123I]FP-CIT SPECT in healthy controls and Parkinson's disease patients. The use of an operator-independent method will be a great advantage in routine clinical studies.

Topics: Aged; Algorithms; Brain; Carrier Proteins; Case-Control Studies; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon; Tropanes

Loss of striatal dopamine (DA) transporters in Parkinson's disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [123I]beta-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20-30 h following the injection of [123I]beta-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand, N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [123I]FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [123I]beta-CIT (24 h following injection) and one with [123I]FP-CIT (3 h following injection). The ratios of specific to non-specific [123I]FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [123I]beta-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [123I]FP-CIT seems as good as [123I]beta-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

Topics: Brain; Carrier Proteins; Case-Control Studies; Cocaine; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Parkinson Disease; Radionuclide Imaging; Receptors, Dopamine; Tropanes

Topics: Carbon Radioisotopes; Corpus Striatum; Humans; Iodine Radioisotopes; Neostriatum; Parkinson Disease; Receptors, Dopamine; Tomography, Emission-Computed, Single-Photon; Tropanes