2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Essential-Tremor

The diagnosis of movement disorders including Parkinson's disease (PD) and essential tremor is determined through clinical assessment. The difficulty with diagnosis of early PD has been highlighted in several recent clinical trials. Studies have suggested relatively high clinical diagnostic error rates for PD and essential tremor. This review was undertaken to clarify the utility of DaT-SPECT imaging with ((123)I)ioflupane (DaTSCAN or DaTscan or ((123)I)FP-CIT) in assisting practitioners in their clinical decision making by visualising the dopamine transporter in parkinsonian cases. In some patients with suspected parkinsonian syndromes, SPECT imaging with ((123)I)ioflupane is useful to assist in the diagnosis and to help guide prognosis and treatment decisions, including avoiding medications that are unlikely to provide benefit. Clinicians ordering ((123)I)ioflupane SPECT should be aware of its limitations and pitfalls and should order scans when there is diagnostic uncertainty or when the scan will be helpful in clinical decision making.

Topics: Antiparkinson Agents; Brain; Decision Support Techniques; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Humans; Neurologic Examination; Nortropanes; Parkinsonian Disorders; Predictive Value of Tests; Tomography, Emission-Computed, Single-Photon; Uncertainty

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

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

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

Topics: Essential Tremor; Humans; Nortropanes; Tomography, Emission-Computed, Single-Photon; Tremor

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

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

In this work, we investigated motor network structure in patients affected by essential tremor (ET) with or without resting tremor, using probabilistic tractography of the cerebello-thalamo-basal ganglia-cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with resting tremor (rET), and twenty-five age- and sex-matched healthy controls were included in the study. All participants underwent whole-brain 3D T1-weighted and diffusion-weighted MRI, and DAT-SPECT. Probabilistic tractography was performed on diffusion data in network mode, reconstructing connections between the different structures of the cerebello-thalamo-basal ganglia-cortical loop. All patients with ET, regardless of the presence of resting tremor, had normal DAT-SPECT, but showed significantly decreased connectivity in the cerebello-thalamo-precentral cortex network bilaterally, compared to healthy controls. In addition, patients with rET showed reduced connectivity in a pathway connecting globus pallidus, caudate, and supplementary motor area, compared to ET and controls. This latter circuit was significantly damaged in the hemisphere contralateral to the side clinically most affected by resting tremor. These findings provide insights upon structural changes underlying the different clinical presentations of ET. Our study demonstrates that ET and rET share common alterations in the cerebello-thalamo-precentral cortex circuit, while rET patients are characterized by specific damage to additional structures of motor network, such as globus pallidus, caudate nucleus, and supplementary motor area. Our findings suggest that ET and rET are different subtypes of the same neurodegenerative disorder.

Topics: Aged; Analysis of Variance; Blinking; Brain; Brain Mapping; Case-Control Studies; Electric Stimulation; Essential Tremor; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Parkinsonian Syndromes are difficult to accurately diagnose and distinguish from other neurological processes such as essential tremor. Until now, physical exam and clinical presentation have been the gold standard for diagnosis (bradykinesia, tremor, rigidity, and postural instability).1 However, this leads to over- or under diagnosis and improper treatment due to variability in presentation and symptoms.1 A nuclear medicine study using I-123 Ioflupane (DaTSCAN) has been developed, which allows accurate differentiation of Parkinsonian Syndromes from other etiologies.1 This study is now widely performed on the mainland, but has never been done in Hawai'i due to its East Coast sourcing and relatively short physical half-life. Through a highly coordinated logistical effort, Tripler Army Medical Center's Nuclear Medicine Department conducted the first DaTSCAN in Hawai'i in April 2016.

Topics: Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Hawaii; Humans; Male; Nortropanes; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon; Young Adult

The usefulness of I-ioflupane imaging for detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain parkinsonian syndromes is well known, especially to differentiate essential tremor from parkinsonisms. Here we present a case of a patient suspected of essential tremor but not responding to standard therapy, in which the results of DaTscan were fundamental to set up an alternative therapeutic approach.

Topics: Corpus Striatum; Diagnosis, Differential; Essential Tremor; Female; Humans; Middle Aged; Nortropanes; Parkinsonian Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Dopamine transporter imaging with (123)I-FP-CIT single photon emission computed tomography (SPECT) is helpful for the differential diagnosis between Parkinsonian syndrome (PS) and essential tremor (ET). Although visual assessment and time-consuming manual evaluation techniques are readily available, a fully objective and automated dopamine transporter quantification technique is always preferable, at least in research and follow-up investigations. Our aim was to develop a novel automated magnetic resonance imaging (MRI)-based evaluation technique of dopamine transporter SPECT images and to compare its diagnostic accuracy with those of the gold-standard visual grading and manual dopamine transporter binding quantification methods.. (123)I-FP-CIT SPECT and MRI sessions were conducted in 33 patients with PS (15 men; mean age: 60.3 ± 9.7 years) and 15 patients with ET (8 men; mean age: 54.7 ± 16.3 years). Striatal dopamine transporter binding was visually classified by 2 independent experts as normal or abnormal grade I, II and III. Caudal and putaminal specific uptake ratios were calculated by both automated MRI-based and manual evaluation techniques.. We found almost perfect agreement (κ = 0.829) between the visual scores by the 2 observers. The automated method showed strong correlation with the visual and manual evaluation techniques and its diagnostic accuracy (sensitivity = 97.0%; specificity = 93.3%) was also comparable to these methods. The automatically determined uptake parameters showed negative correlation with the clinical severity of parkinsonism. Based on ordinal regression modelling, the automated MRI-based method could reliably determine the visual grading scores.. The novel MRI-based evaluation of (123)I-FP-CIT SPECT images is useful for the differentiation of PS from ET.

Topics: Adult; Aged; Electronic Data Processing; Essential Tremor; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinsonian Disorders; ROC Curve; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

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

Mild parkinsonian features can be observed in patients with essential tremor (ET). Although dopamine transporter (DAT) imaging is usually normal in ET, some studies found mild dopaminergic deficit in ET patients compared to healthy controls (HC). We analyzed clinical and DAT imaging data in ET patients with and without parkinsonian features. Thirty-nine ET patients with and without parkinsonian features and 13 HC underwent detailed examination by a movement disorders neurologist and 123-I ioflupane SPECT. Two independent radiologists "blinded" to the clinical diagnosis analyzed images visually and by semi-quantitative calculation of striatal binding ratios in different volumes of interests. ET patients were divided into pure ET group (no parkinsonian features, n = 22), ET-P [one parkinsonian feature not sufficient for the clinical diagnosis of Parkinson's disease (PD), n = 9], and ET + PD (two or more parkinsonian features meeting diagnostic criteria for PD, n = 8). As expected, ET + PD patients had the lowest striatal binding ratios. We also found a trend toward slightly lower striatal binding ratios in ET patients ET compared to HC, especially in caudate nucleus. There was no significant correlation between striatal binding ratios, ET severity or duration. Patients with ET and parkinsonian features represent a heterogeneous group that includes ET + PD and ET-P. The latter group shares some clinical features with PD but has no dopaminergic deficit on DAT imaging as determined by visual image interpretation. On the other hand, minimal dopaminergic deficit (as compared to controls) is detected in some ET patients with semi-quantitative image analysis, although the pattern may be different from that of PD.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Mapping; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Male; Middle Aged; Nortropanes; Parkinsonian Disorders; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon

Diagnosis of Parkinson's disease (PD) can be difficult in the early stages of the disease. The aim of the study described here was to assess the correlation between transcranial sonography (TCS) and (123)I-FP-CIT ([(123)I]ioflupane, N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[(123)I]iodophenyl)nortropane) SPECT (single photon emission computed tomography) findings and the diagnosis of PD. A total of 49 patients were enrolled in the study: 29 patients with PD, 7 patients with other parkinsonian syndromes, 11 patients with essential tremor and 2 with psychogenic movement disorder. Substantia nigra echogenicity was measured using TCS. SPECT was performed using DaTSCAN ([(123)I]ioflupane). TCS and SPECT findings were correlated in 84% of patients, with κ = 0.62 (95% confidence interval: 0.38-0.86). TCS-measured substantia nigra echogenicity and SPECT-measured striatal binding ratio were negatively correlated (r = -0.326, p = 0.003). TCS/SPECT sensitivity, specificity and positive and negative predictive values for the diagnosis of PD were 89.7%/96.6%, 60.0%/70.0%, 76.5%/82.4% and 80.0%/93.3%, respectively. Both positive TCS and SPECT findings correlated significantly with the diagnosis of PD (κ = 0.52, 95% confidence interval: 0.27-0.76, and κ = 0.69, 95% confidence interval: 0.49-0.90, respectively).

Topics: Adult; Aged; Diagnosis, Differential; Essential Tremor; Female; Humans; Male; Middle Aged; Parkinsonian Disorders; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes; Ultrasonography, Doppler, Transcranial

Essential tremor is an abnormal movement characterized by postural and/or kinetic tremor. In some essential tremor patients, rest tremor (RT) is observed but it is not clear if this RT is a feature of essential tremor or a symptom of Parkinson's disease (PD). I123-FP-CIT single-photon emission tomography is used to distinguish essential tremor and PD.. To analyse I123-FP-CIT single-photon emission tomography in a larger series of patients with mixed tremor (i.e. action tremor associated with RT) without PD criteria.. We studied 33 consecutives patients (18 men and 15 women) with mixed tremor, clinically and by neuroimaging in all cases.. I123-FP-CIT single-photon emission tomography was abnormal in 25 of our patients (75.7%) with mixed tremor, and we noted a reduced uptake mostly in the putamen. In our patients with abnormal imaging, RT was unilateral in 52%. In 15 of these 25 patients, putaminal reduced uptake was bilateral and symmetrical. In the other 10 patients, putaminal reduced uptake was asymmetrical or unilateral. In these 10 cases, six had a unilateral RT corresponding to (crossed) predominant reduced uptake in three cases. In our patients with normal imaging, RT was unilateral in 87.5%.. This study shows that mixed tremor is a heterogeneous entity. The majority of patients with mixed tremor showed nigrostriatal dysfunction on I123-FP-CIT single-photon emission tomography, suggesting that mixed tremor may be a parkinsonian syndrome rather than a clinical variant of essential tremor.

Topics: Aged; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Functional Laterality; Functional Neuroimaging; Humans; Iodine Radioisotopes; Male; Putamen; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tremor; Tropanes

Studies have demonstrated brain iron deposition in neurodegenerative disease and in normal aging. Data on this topic are lacking in essential tremor (ET). The aim of our study was to investigate brain iron content in patients with ET, using quantitative magnetic resonance imaging (MRI) T2*-relaxometry. We enrolled 24 patients with ET and 25 age-matched healthy controls. Subjects were examined using a 3T MRI scanner. The protocol included conventional MRI sequences and quantitative T2*-relaxometry. Whole-brain voxel-based analyses showed significant differences in T2* values in bilateral globus pallidus, substantia nigra, and in right dentate nucleus (P < .001 uncorrected). In the bilateral pallidum, differences survived family-wise-error (FWE) correction for multiple comparisons (P < .05). The present study provides the first evidence of increased brain iron accumulation in ET patients. Our results are suggestive of a possible involvement of motor systems outside of the cerebellum/cerebellar pathway and, more specifically, of the globus pallidus.

Topics: Aged; Brain Chemistry; Dentate Gyrus; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Functional Laterality; Globus Pallidus; Humans; Image Processing, Computer-Assisted; Iron; Magnetic Resonance Imaging; Male; Middle Aged; Radiopharmaceuticals; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; 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

Previous studies have compared the accuracy of spiral analysis in distinguishing essential tremor (ET) from PD. In this study, we have used this technique to distinguish cases of tremulous PD (TDPD) (N = 24) from tremulous parkinsonian subjects without evidence of dopaminergic deficit (N = 41).. All patients were characterized on clinical and (123)I-N-ω-fluoro-propyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) SPECT scan data, which were concordant in every case. All analyses were carried out by observers blinded to the clinical details and supplied with just the spiral drawings, from which tremor severity (TS), 3-turn spiral diameter (3TD), and spiral density (SD) were measured.. The spirals drawn by TDPD cases had significantly smaller 3TD (P = 0.029) and greater SD (P = 0.0082) than those with normal FP-CIT scans. There was no significant difference in the TS between the two groups (P = 0.11). The sensitivity and specificity of TS were 62.5% and 65.0%, 3TD were 75% and 56.7%, and SD were 30.4% and 82.5%, respectively, in predicting the correct classification. Further analyses combining these factors into pairs, showed that the respective sensitivities and specificities of (1) TS × 3TD were 75.0% and 40.0%, (2) TS/SD were 56% and 70.0%, and (3) 3TD/SD were 87.0% and 40.0%.. There are significant differences in the 3TD and SD of spirals drawn by tremulous patients with normal versus abnormal FP-CIT scans. Spiral analysis may have some clinical value in helping to distinguish tremulous parkinsonian patients with normal presynaptic dopaminergic imaging from tremulous PD patients, providing results similar to those reported for expert movement disorder neurologists using standardized videotaped examinations.

Topics: Adult; Aged; Aged, 80 and over; Essential Tremor; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinsonian Disorders; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Tomography, Emission-Computed, Single-Photon; Tropanes

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

(123)I-FP-CIT-SPECT is useful in the differential diagnosis of Parkinson's disease (PD) and tremor syndromes. Recently, there have been reports on normal nigrostriatal uptake of radio ligands in PD patients, referred to as scans without evidence of dopaminergic deficit (SWEDDs). Furthermore, a dopaminergic deficit has been described in some cases of different tremor types. We sought to clarify the occurrence of SWEDDs in PD and a possible association of various tremor types with PD. We performed a retrospective case analysis of 125 patients with diagnostically uncertain Parkinsonian or non-Parkinsonian tremor syndromes with clinical assessments and (123)I-FP-CIT-SPECT. A total of 36/40 (90%) patients with the predominant clinical feature of a postural and/or kinetic tremor showed normal DAT SPECT; 73/85 (86%) with predominant clinical symptoms of PD showed abnormal DAT SPECT with lower overall radio ligand uptake and a significant asymmetry contralateral to the clinically more affected side. In all, 4/40 (10%) of non-Parkinsonian tremor patients had abnormal DAT SPECT, but no corresponding asymmetry of radio ligand uptake. Probable essential tremor was considered clinically in follow-up assessments although final diagnosis of these four tremor cases remains inconclusive. A total of 12/85 (14%) clinically suspected PD patients had normal DAT SPECT (SWEDDs). Clinical reassessment identified two patients with dystonic tremor. Five patients with a positive response to levodopa remained unclear. In four cases of suspected PD with normal DAT SPECT, non-neurologic diseases were identified. One case showed a complete and spontaneous remission of symptoms. DAT SPECT offers an objective method to confirm or exclude a dopaminergic deficit in tremor predominant parkinsonism for clinically inconclusive cases. There was no evidence of a decrease in DAT binding in the majority of patients with postural and/or kinetic tremor. The striatal asymmetry index is a further helpful tool for differentiating PD from non-PD tremor syndromes.

Topics: Aged; Brain; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Essential Tremor; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinsonian Disorders; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

The aim of this study was to quantitatively evaluate the striatal uptake in 3 groups of patients: essential tremor (ET), drug-induced parkinsonism (DIP), and Parkinson disease (PD), using a voxel-based methodology and volumes of interests (VOIs) analysis.. Sixty patients from the Neurology Department Movement Disorders outpatient clinic in a tertiary hospital with I-123-FP-CIT SPECT were selected. After a clinical follow-up period of 2 years, a final clinical diagnosis of DIP was established for 20 patients (first group); 20 patients were diagnosed with ET (second group), and the third group was made up of 20 patients with a qualitatively pathologic SPECT who were diagnosed with PD.Once processed, DIP studies were spatially normalized to Montreal Neurologic Institute space and an average image was computed to create an I-123-FP-CIT SPECT template using statistical parametric mapping (SPM). Then all the I-123-FP-CIT images from all groups (DIP, ET, and PD) were registered to the new template. VOIs were defined in a digital atlas in Montreal Neurologic Institute space (caudate nucleus, putamen, and occipital cortex). Finally, mean counts were extracted from all VOIs and putamen-occipital and caudate-occipital ratios were computed. Analysis of variance tests were performed with all ratios.A SPM study of patterns evaluated the efficacy of the automated technique to determine whether the significant differences among groups corresponded to the same regions that the method purported to evaluate.. The analysis of variance test revealed significant differences between DIP and ET as compared with PD, both in the putamen and in the caudate nucleus. There were significant differences between DIP and ET populations only in the putamen but not in the caudate.The SPM found a lower uptake in the PD group in comparison with the ET and DIP groups. Therefore, in the organic parkinsonism cases, the most significant changes in uptake decrease were found in the putamen nuclei when compared with the DIP and the ET cases. No significant changes were observed between the ET and DIP groups.. This study provides a fairly simple, reproducible, and useful methodology to be applied in everyday practice to quantify the studies of dopamine transporters using FP-CIT.We present the different ratios for putamen and caudate nucleus for 3 different groups with FP-CIT images. We obtained an optimal discrimination threshold value between the reference population and the pathologic population for the putamen ratio.

Topics: Aged; Essential Tremor; Female; Humans; Magnetic Resonance Imaging; Male; Models, Statistical; Neostriatum; Parkinsonian Disorders; Radionuclide Imaging; ROC Curve; Tropanes

To investigate over time changes in striatal dopamine transporter (DAT), we performed two sequential N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane single photon computed tomography (SPECT) scans in 20 subjects with essential tremor (ET), in 13 with Parkinson disease (PD) and in 23 healthy controls (HC, one scan only). We also performed an [(99m)Tc]ethyl cysteinate dimer bicisate SPECT exam for regional brain network analysis in 9 ET, in a second group of 18 PD (9 with tremor, tPD and 9 akinetic-rigid dominant, arPD) and in 8 HC. PD subjects had a reduced DAT binding in comparison to ET and HC with an annual decline rate of 7.3% in the contralateral putamen. There were no mean uptake differences between ET and HC at baseline and no uptake loss over time in ET. A discriminant analysis grouped 30% (first scan) and 5% (second scan) of ET as PD and a partition analysis showed overlap between ET and PD for caudate nucleus uptake. Spatial covariance analysis revealed that the expression of the PD-related regional pattern separated both tPD and arPD from ET and HC. In conclusion, PD and ET do not share a common pattern of dopaminergic loss over time. However, mild impairment of dopamine transporter in the caudate nucleus may contribute to tremor onset in ET.

Topics: Aged; Aged, 80 and over; Brain; Discriminant Analysis; Essential Tremor; Female; Humans; Iodine Isotopes; Male; Middle Aged; Neural Pathways; Severity of Illness Index; 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 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

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

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

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

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

We report a family with 5 affected individuals manifesting either essential tremor (ET), Parkinsonism, or both, consistent with pseudo-dominant inheritance of PARK2. Two homozygotes presented postural and kinetic tremor several years before the onset of Parkinsonism. Postural and kinetic tremor mimicking ET was the only feature in 1 homozygous and 2 heterozygous carriers of the mutation. Striatal dopamine transporter density was reduced in accordance with phenotype and number of mutated alleles. In 3 homozygotes and 1 heterozygote, a 2-year follow-up single photon emission computed tomography suggested no progression of nigrostriatal deficit.

Topics: Corpus Striatum; Diagnosis, Differential; Essential Tremor; Genes, Dominant; Humans; Iodine Radioisotopes; Mutation, Missense; Parkinsonian Disorders; Pedigree; Phenotype; Point Mutation; Polymerase Chain Reaction; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes; Ubiquitin-Protein Ligases

(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

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

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

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

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