2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Multiple-System-Atrophy

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

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

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

To validate the role of the dopamine transporter (DAT) imaging as a biomarker in multiple system atrophy (MSA), we analyzed the association between spatial patterns of [. Sixty-five patients with MSA who underwent [. Of the 65 patients, 42 presented with parkinsonian subtype of MSA, and 23 presented with cerebellar subtype of MSA (mean age 63.7 ± 9.3 years; disease duration, 1.8 ± 1.8 years). Each PC represents a specific pattern of degeneration: PC1 and PC2 were associated with the DAT binding of the entire putamen and the posterior putamen, respectively. PC3 was associated with increased [. The spatial pattern of DAT binding can reflect distinct clinical features of MSA and provides insight into the underlying pathophysiology of a broad spectrum of clinical features in MSA.

Topics: Adult; Aged; Aged, 80 and over; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Multiple System Atrophy; Neuroimaging; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

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

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

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

Multiple system atrophy (MSA) may develop levodopa-induced dyskinesia, which is dystonic and predominant in the orofacial region. We aimed to characterize the patterns of presynaptic dopaminergic degeneration in patients with MSA and dyskinesia using. A single center cross-sectional retrospective study was conducted using consecutive chart review of patients with probable MSA who underwent. Twenty-five patients with probable MSA who had undergone dopamine transporter imaging were identified (age [mean ± standard error], 62.5 ± 1.7 years; disease duration, 48.8 ± 7.0 months). Four of them presented dyskinesia and 21 of patients did not. Twenty-five patients with MSA were visually classified into five grades: one Grade 1 (normal), two Grade 2 (eagle wing), three Grade 3 (mixed), nine Grade 4 (egg shape), and ten Grade 5 (burst striatum). All patients with MSA and dyskinesia were classified into Grade 5. Visual grading significantly correlated with disease duration and levodopa responsiveness.. Severe presynaptic dopaminergic dysfunction in

Topics: Aged; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Multiple System Atrophy; Neostriatum; Neurodegenerative Diseases; Presynaptic Terminals; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Tropanes

The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology.. To investigate the difference in clinical features between MSA patients with predominantly pre-synaptic nigrostriatal dysfunction and those with trans-synaptic nigrostriatal dysfunction.. Parkinsonian features were significantly more severe in the MSA-STR group than in the MSA-SNpc group (P = .005) and cerebellar ataxia was significantly more severe in the MSA-SNpc group (P = .036). The cerebellar type of MSA was significantly more common in the MSA-SNpc group (P = .001). There was no difference in age at onset, disease duration at the time of study, or Mini-Mental Status Examination scores between the groups.. Patients with MSA showed distinct clinical features depending on whether the pattern of nigrostriatal dysfunction was predominantly pre-synaptic or trans-synaptic.

Topics: Adult; Aged; Case-Control Studies; Cerebellar Ataxia; Corpus Striatum; Female; Fluorodeoxyglucose F18; Functional Neuroimaging; Humans; Male; Middle Aged; Multiple System Atrophy; Neural Pathways; Parkinsonian Disorders; Positron-Emission Tomography; Presynaptic Terminals; Putamen; Substantia Nigra; 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

We aimed at examining sensitivity of combined visual and semi-quantitative. 3/155 (2.1%) subjects with degenerative parkinsonism (1 CBS, 1 MSA-C and 1 PD) and 1/53 (1.9%) with DLB had a normal visual SPECT. Subsequent semi-quantitative analysis showed mild striatal uptake impairment for the DLB and the PD subject. Therefore, only two patients (1 CBS and 1 MSA) had a strictly normal combined assessment.. The present study shows that SWEDD cases represent a negligible proportion of patients with degenerative conditions (1.3%), when stringent diagnostic criteria are applied, a thorough follow-up is performed and visual SPECT analysis is combined with precise semi-quantitative assessment.

Topics: Adult; Aged; Aged, 80 and over; Brain; Dopamine; Female; Humans; Lewy Body Disease; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Parkinsonian Disorders; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

We describe an 84-year-old man with anti-NH2-terminal of α-enolase antibody-positive Hashimoto encephalopathy that clinically mimicked multiple system atrophy who underwent investigation by dopamine transporter SPECT before and after immunotherapy. Before treatment, dopamine transporter SPECT showed reduced striatal I-ioflupane binding, with a mean specific binding ratio of 2.42, even though he had no apparent parkinsonism. After immunotherapy, mean specific binding ratio was improved to 3.22. Dopamine transporter SPECT was useful in this case to detect subclinical striatal dysfunction, and evaluation both before and after immunotherapy helped to distinguish between neurodegenerative disease and neuroimmunological disorder.

Topics: Aged, 80 and over; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Encephalitis; Hashimoto Disease; Humans; Immunotherapy; Male; Multiple System Atrophy; Nortropanes; Phosphopyruvate Hydratase; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Cerebellar Ataxia; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Levodopa; Male; Middle Aged; Multiple System Atrophy; Positron-Emission Tomography; Tropanes

Topics: Carbolines; Female; Humans; Male; Multiple System Atrophy; Positron-Emission Tomography; Protein Binding; Putamen; Tropanes

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

Topics: Dopamine Plasma Membrane Transport Proteins; Humans; Male; Middle Aged; Multiple System Atrophy; Positron-Emission Tomography; Radiopharmaceuticals; Tropanes

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

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

Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.

Topics: Adult; Aged; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Multiple System Atrophy; Radiopharmaceuticals; Substantia Nigra; Tomography, Emission-Computed, Single-Photon; Tropanes

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

Recurrent falls in older people are commonly associated with abnormalities that involve several parts of the central nervous system, especially with basal ganglion pathology. The aim of the present study was to evaluate the integrity of striatal dopamine transporters (DaTs) by use of (123)I-N-3-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) SPECT of striatal DaTs in patients with recurrent sudden falls.. Twenty-one patients without a definite neurologic diagnosis for recurrent sudden falls were enrolled in a cross-sectional study. SPECT with a DaT ligand was performed 180 min after injection of 185 MBq of (123)I-FP-CIT with a dual-head gamma-camera.. DaT SPECT findings were normal in 15 of 21 patients (71%). Of those, 73% had abnormal MRI findings suggestive of atherosclerotic lesions. Eleven patients with normal DaT SPECT findings had mild parkinsonian symptoms. There was no correlation of the SPECT results with patient age, duration of occurrence of falls, or frequency of falls, and there was no significant difference in the relative distributions of SPECT findings between patients with and patients without parkinsonian symptoms or vascular risk factors.. Recurrent sudden falls are, in most cases, not attributable to the degeneration of the nigrostriatal system.

Topics: Accidental Falls; Aged; Aged, 80 and over; Corpus Striatum; Dementia, Vascular; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Multiple System Atrophy; Parkinsonian Disorders; Radiopharmaceuticals; Supranuclear Palsy, Progressive; 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