CSF-derived extracellular vesicles from patients with Parkinson's disease induce symptoms and pathology.

Parkinson's disease is characterized by the gradual appearance of intraneuronal inclusions that are primarily composed of misfolded α-synuclein protein, leading to cytotoxicity and neural death. Recent in vitro and in vivo studies suggest that misfolded α-synuclein may spread transcellularly in a prion-like manner, inducing pathological aggregates in healthy neurons, and is disseminated via secretion of extracellular vesicles. Accordingly, extracellular vesicles derived from brain lysates and CSF of patients with Parkinson's disease were shown to facilitate α-synuclein aggregation in healthy cells. Prompted by the hypothesis of Braak and colleagues that the olfactory bulb is one of the primary propagation sites for the initiation of Parkinson's disease, we sought to investigate the role of extracellular vesicles in the spread of α-synuclein and progression of Parkinson's disease through the olfactory bulb. Extracellular vesicles derived from the CSF of patients diagnosed with Parkinson's disease or with a non-synucleinopathy neurodegenerative disorder were administered intranasally to healthy mice, once daily over 4 days. Three months later, mice were subjected to motor and non-motor tests. Functional impairments were elucidated by histochemical analysis of midbrain structures relevant to Parkinson's disease pathology, 8 months after EVs treatment. Mice treated with extracellular vesicles from the patients with Parkinson's disease displayed multiple symptoms consistent with prodromal and clinical-phase Parkinson's disease such as hyposmia, motor behaviour impairments and high anxiety levels. Furthermore, their midbrains showed widespread α-synuclein aggregations, dopaminergic neurodegeneration, neuroinflammation and altered autophagy activity. Several unconventional pathologies were also observed, such as α-synuclein aggregations in the red nucleus, growth of premature grey hair and astrogliosis. Collectively, these data indicate that intranasally administered extracellular vesicles derived from the CSF of patients with Parkinson's disease can propagate α-synuclein aggregation in vivo and trigger Parkinson's disease-like symptoms and pathology in healthy mice.

Oculometric measures as a tool for assessment of clinical symptoms and severity of Parkinson's disease.

Abnormalities of oculometric measures (OM) are widely described in people with Parkinson's disease (PD). However, knowledge of correlations between abnormal OM, disease severity and clinical assessment in PD patients is still lacking. To evaluate these correlations, PD patients (215 patients, mean age 69 ± 9.1 years, 79 females) with severe (H&Y > 3) and mild to moderate (H&Y ≤ 2) disease, and 215 age-matched healthy subjects were enrolled. All patients were evaluated using MDS-UPDRS and an oculometric test using computer vision and deep learning algorithms. Comparisons of OM between groups and correlations between OM and MDS-UPDRS scores were calculated. Saccadic latency (ms) was prolonged in patients with severe compared with mild to moderate disease (pro-saccades: 267 ± 69 vs. 238 ± 53, p = 0.0011; anti-saccades: 386 ± 119 vs. 352 ± 106, p = 0.0393) and in patients with mild to moderate disease versus healthy subjects (pro-saccades: 238 ± 53 vs. 220 ± 45, p = 0.0003; anti-saccades: 352 ± 106 vs. 289 ± 71, p < 0.0001). Error rate (%) was higher among patients with severe (64.06 ± 23.08) versus mild to moderate disease (49.84 ± 24.81, p = 0.0001), and versus healthy subjects (49.84 ± 24.81 vs. 28.31 ± 21.72, p = 0.00001). Response accuracy (%) was lower for patients with severe (75.66 ± 13.11) versus mild to moderate disease (79.66 ± 13.56, p = 0.0462), and versus healthy subjects (79.66 ± 13.56 vs. 90.27 ± 8.79, p < 0.0001). Pro- and anti-saccadic latency, error rate and accuracy were correlated with MDS-UPDRS scores (r = 0.32, 0.28, 0.36 and -0.30, respectively, p < 0.0001) and similar correlations were found with its axial subscore (R = 0.38, 0.29, 0.44, and -0.30, respectively, p < 0.0001). Several OM were different in patients under levodopa treatment. OM worsened as PD severity increases, and were correlated with MDS-UPDRS scores. Using OM can be implemented for PD patients' assessment as a tool to follow disease progression.

Levodopa responsiveness in Parkinson's disease: harnessing real-life experience with machine-learning analysis.

Responsiveness to levodopa varies greatly among patients with Parkinson's disease (PD). The factors that affect it are ill defined. The aim of the study was to identify factors predictive of long-term response to levodopa. The medical records of 296 patients with PD (mean age of onset, 62.2 ± 9.7 years) were screened for demographics, previous treatments, and clinical phenotypes. All patients were assessed with the Unified PD Rating Scale (UPDRS)-III before and 3 months after levodopa initiation. Regression and machine-learning analyses were used to determine factors that are associated with levodopa responsiveness and might identify patients who will benefit from treatment. The UPDRS-III score improved by ≥ 30% (good response) in 128 patients (43%). On regression analysis, female gender, young age at onset, and early use of dopamine agonists predicted a good response. Time to initiation of levodopa treatment had no effect on responsiveness except in patients older than 72 years, who were less responsive. Machine-learning analysis validated these factors and added several others: symptoms of rigidity and bradykinesia, disease onset in the legs and on the left side, and fewer white vascular ischemic changes, comorbidities, and pre-non-motor symptoms. The main determinants of variations in levodopa responsiveness are gender, age, and clinical phenotype. Early use of dopamine agonists does not hamper levodopa responsiveness. In addition to validating the regression analysis results, machine-learning methods helped to determine the specific clinical phenotype of patients who may benefit from levodopa in terms of comorbidities and pre-motor and non-motor symptoms.

High Glucosylceramides and Low Anandamide Contribute to Sensory Loss and Pain in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) causes chronic pain in two-thirds of patients, in part originating from sensory neuropathies. The aim of the present study was to describe the phenotype of PD-associated sensory neuropathy and to evaluate its associations with lipid allostasis, the latter motivated by recent genetic studies associating mutations of glucocerebrosidase with PD onset and severity. Glucocerebrosidase catalyzes the metabolism of glucosylceramides. METHODS: We used quantitative sensory tests, pain ratings, and questionnaires and analyzed plasma levels of multiple bioactive lipid species using targeted lipidomic analyses. The study comprised 2 sets of patients and healthy controls: the first 128 Israeli PD patients and 224 young German healthy controls for exploration, the second 50/50 German PD patients and matched healthy controls for deeper analyses. RESULTS: The data showed a 70% prevalence of PD pain and sensory neuropathies with a predominant phenotype of thermal sensory loss plus mechanical hypersensitivity. Multivariate analyses of lipids revealed major differences between PD patients and healthy controls, mainly originating from glucosylceramides and endocannabinoids. Glucosylceramides were increased, whereas anandamide and lysophosphatidic acid 20:4 were reduced, stronger in patients with ongoing pain and with a linear relationship with pain intensity and sensory losses, particularly for glucosylceramide 18:1 and glucosylceramide 24:1. CONCLUSIONS: Our data suggest that PD-associated sensory neuropathies and PD pain are in part caused by accumulations of glucosylceramides, raising the intriguing possibility of reducing PD pain and sensory loss by glucocerebrosidase substituting or refolding approaches. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The role of exposure to pesticides in the etiology of Parkinson's disease: a 18F-DOPA positron emission tomography study.

Susceptibility to Parkinson's disease (PD) is believed to involve an interaction between genetic and environmental factors. The role of pesticides as a risk factor of PD and neurodegeneration remains controversial. An asymmetric decrease in ligand uptake on 18F-DOPA positron emission tomography (PET), especially in the dorsal putamen, is a sensitive marker of PD. The aim of this study was to examine the pattern of ligand uptake on 18F-DOPA PET in patients with PD exposed or not exposed to pesticides. The main sample included 26 Israeli patients with PD, 13 who were exposed to pesticides and 13 who were not, matched for age and disease duration. All underwent 18F-DOPA PET imaging, and an asymmetry index of ligand uptake between the ipsilateral and contralateral caudate, putamen, and whole striatum was calculated. No significant between-group differences were found in demographic variables, clinical asymmetry index (P = 0.15), or asymmetry index of ligand uptake in the putamen (P = 0.84), caudate (P = 0.78) and striatum (P = 0.45). Comparison of the 18F-DOPA results of the Israeli cohort with those of 17 non-pesticide-exposed patients with PD from Austria yielded no significant differences, further validating our findings. Our observations suggest that although exposure to pesticides might be a risk factor for PD, it does not have an effect on the asymmetry pattern in the nigrostriatal system over non-exposure. We assume that once the disease process is initiated in pesticide-exposed patients, the pathogenic mechanism does not differ from that of idiopathic PD.

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society.

VPS35 mutations in Parkinson disease.

The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with ¹8F-ML-10.

PURPOSE: Early assessment of tumor response to therapy is vital for treatment optimization for the individual cancer patient. Induction of apoptosis is an early and nearly universal effect of anticancer therapies. The purpose of this study was to assess the performance of (18)F-ML-10, a novel PET radiotracer for apoptosis, as a tool for the early detection of response of brain metastases to whole-brain radiation therapy (WBRT). MATERIALS AND METHODS: Ten patients with brain metastases treated with WBRT at 30 Gy in ten daily fractions were enrolled in this trial. Each patient underwent two (18)F-ML-10 PET scans, one prior to the radiation therapy (baseline scan), and the second after nine or ten fractions of radiotherapy (follow-up scan). MRI was performed at 6-8 weeks following completion of the radiation therapy. Early treatment-induced changes in tumor (18)F-ML-10 uptake on the PET scan were measured by voxel-based analysis, and were then evaluated by correlation analysis as predictors of the extent of later changes in tumor anatomical dimensions as seen on MRI scans 6-8 weeks after completion of therapy. RESULTS: In all ten patients, all brain lesions were detected by both MRI and the (18)F-ML-10 PET scan. A highly significant correlation was found between early changes on the (18)F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9). CONCLUSION: These results support the potential of (18)F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT.

Respiratory distress: an unrecognized non-motor phenomenon in patients with parkinsonism.

Although respiratory abnormalities are associated with parkinsonism, patients rarely complain of dyspnea. This study describes ten patients with parkinsonism and symptoms of dyspnea and respiratory distress that were unexplained by a pulmonary or cardiac abnormality or a psychological problem. Suggested underlying mechanisms are a central pathology affecting respiratory rhythm generation at the brainstem or lack of coordination of the respiratory muscles causing involuntary movements of the diaphragm. Dyspnea and respiratory distress should be included among the non-motor symptoms of parkinsonism.

Patient and caregiver perceptions of the social impact of advanced Parkinson's disease and dyskinesias.

Parkinson's disease (PD) exacts a physical and emotional toll on both patients and family. The aim of this study was to compare patient and caregiver perceptions of the social consequences of basic symptoms of PD and levodopa-induced dyskinesias. Forty patients with PD and dyskinesias and 35 of their caregivers completed a self-report questionnaire on the impact of PD and dyskinesias on their feelings of security and embarrassment and participation in family/social events, and indicated their preference for the "on" (with dyskinesias) or the "off" (without dyskinesias) state. The patients scored significantly higher than the caregivers did on the negative social impact of the disease in general (p = 0.002) and of the dyskinesias in particular (p = 0.03). Nevertheless, the patients expressed a significantly greater preference for the "on" state (83 %) than the caregivers (59 %) (p = 0.03). Preferences turned to be reverse in direction among spouse-caregivers who significantly preferred the "off" state (54 %) than the patients (25 %) (p = 0.04). Although patients have a worse perception of the effects of PD than their caregivers do, they prefer the more independent "on" state, whereas their caregivers prefer the "off" state.

Management of advanced Parkinson's disease in Israel: Clinicians viewpoint and action items.

Parkinson's disease (PD) is taking a staggering toll on healthcare systems worldwide, with the bulk of the expenditures invested in the late stages of the disease. Considering the rising life expectancy and the increasing prevalence of PD across the globe, a clear understanding of the early signs and treatment options available for advanced PD (APD), will facilitate tailoring management programs and support services. This task is complicated by the lack of both global consensus in defining APD and standardized care guidelines. This perspective prepared by a panel of movement disorder specialists, proposes to extend and optimize currently accepted PD coding to better reflect the diverse disease manifestations, with emphasis on non-motor features. The panel seeks to promote timely diagnosis by adjustment of evaluation tools for use by community neurologists and suggests modification of eligibility criteria for advanced therapy. Moreover, it advocates multidisciplinary assessments of APD patients to drive personalized, patient-centered and holistic management. Overall, earlier and more targeted intervention is expected to markedly improve patient quality of life.

Task Force Consensus on Nosology and Cut-Off Values for Axial Postural Abnormalities in Parkinsonism.

Background: There is no consensus with regard to the nosology and cut-off values for postural abnormalities in parkinsonism. Objective: To reach a consensus regarding the nosology and cut-off values. Methods: Using a modified Delphi panel method, multiple rounds of questionnaires were conducted by movement disorder experts to define nosology and cut-offs of postural abnormalities. Results: After separating axial from appendicular postural deformities, a full agreement was found for the following terms and cut-offs: camptocormia, with thoracic fulcrum (>45°) or lumbar fulcrum (>30°), Pisa syndrome (>10°), and antecollis (>45°). "Anterior trunk flexion," with thoracic (≥25° to ≤45°) or lumbar fulcrum (>15° to ≤30°), "lateral trunk flexion" (≥5° to ≤10°), and "anterior neck flexion" (>35° to ≤45°) were chosen for milder postural abnormalities. Conclusions: For axial postural abnormalities, we recommend the use of proposed cut-offs and six unique terms, namely camptocormia, Pisa syndrome, antecollis, anterior trunk flexion, lateral trunk flexion, anterior neck flexion, to harmonize clinical practice and future research.

Residual striatal dopaminergic nerve terminals in very long-standing Parkinson's disease: a single photon emission computed tomography imaging study.

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long-standing PD has not yet been specifically explored. Therefore, we performed [(123)I]-FP-CIT single photon emission computed tomography (SPECT) in 15 patients with very long-standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [(123)I]-FP-CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD.

ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study.

INTRODUCTION: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations. METHODS: This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC. During Period-2, 16 patients were randomized to receive 7 days treatment with ND0612 or ND0612 plus oral entacapone. Reduction in OFF time was analyzed as an exploratory measure using a futility design with a predefined margin of 1.6 h. RESULTS: ND0612 was well-tolerated; most patients experienced infusion site nodules (95% vs. 56% with placebo), which all resolved without sequelae. Patients treated with adjunct ND0612 during Period-1 avoided deep troughs in levodopa plasma levels and had a decreased fluctuation index versus placebo (1.6 ± 0.5 vs 3.1 ± 1.6 at end of Period-1, respectively). In Period-2, the coadministration of entacapone with continuous ND0612 SC infusion translated to an increase in mean levodopa AUC0-10h compared to baseline. Exploratory efficacy analysis of Period 1 showed mean ± SD OFF time reductions of -2.13 ± 2.24 [90%CI: -2.8, ∞] hours (p = 0.84 using H0 of µ0 ≤-1.6). CONCLUSION: Levodopa/carbidopa infusion with ND0612 was generally well-tolerated and resulted in reduced fluctuations in plasma levodopa concentrations when given with SoC oral levodopa. ND0612 met the efficacy endpoint for the futility design.

Unilateral lower limb rest tremor is not necessarily a presenting symptom of Parkinson's disease.

Lower leg rest tremor is an uncommon symptom of neurological disease. Review of the files of 16 patients who presented with lower leg tremor (average age 58 +/- 16 years; average disease duration 6.8 +/- 8.5 years) yielded a diagnosis of Parkinson's disease (PD) in 5 and probable multiple system atrophy (MSA) in 3. In 4 patients with an indeterminate diagnosis, cardiac MIBG SPECT was positive in 3, indicating PD, and negative in one, suggesting MSA. Two patients each had psychogenic tremor and drug-induced parkinsonism. Although lower leg tremor is considered an unusual presentation of PD, it should raise suspicions of MSA and other neurodegenerative disorders.

Presentation, diagnosis, and management of multiple system atrophy in Europe: final analysis of the European multiple system atrophy registry.

Multiple system atrophy (MSA) is a Parkinson's Disease (PD)-like α-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas.

Lesions outside the CNS in Parkinson's disease.

Parkinson's disease (PD) is not a simple movement disorder induced just by loss of dopaminergic neurons in the substantia nigra pars compacta. Apparently, the substantia nigra is not the only or the first brain region damaged in PD. Moreover, older and recent studies have shown that the degenerative process in PD is much more extensive and affects not only the central nervous system (CNS) but also the peripheral autonomic nervous system and the organs outside the brain that the latter innervates. These include mainly the gastrointestinal tract, the heart, kidneys, urogenital system, and skin. Additional extra-CNS organs that are involved in PD include the eye and the adrenal gland. This article reviews the anatomical, physiological, and clinical features of extracerebral manifestations of PD, and describes their relevance to the etiology and pathogenesis of the disease. It establishes this illness as a systemic CNS and peripheral disorder that warrants new hypotheses regarding its causation and progression.

Use of a single [123I]-FP-CIT SPECT to predict the severity of clinical symptoms of Parkinson disease.

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