Bridging Ontologies of Neurological Conditions: Towards Patient-centered Data Practices in Digital Phenotyping Research and Design.

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy (S37.005)

Multiple system atrophy (MSA) and Parkinson’s disease (PD) belong to alpha-synucleinopathy, but they have very different clinical courses and prognoses. An imaging biomarker that can differentiate between the two diseases early in the disease course is desirable for appropriate treatment. Neuroimaging-based brain age paradigm provides an individualized marker to differentiate aberrant brain aging patterns in neurodegenerative diseases. In this study, patients with MSA (N = 23), PD (N = 33), and healthy controls (N = 34; HC) were recruited. A deep learning approach was used to estimate brain-predicted age difference (PAD) of gray matter (GM) and white matter (WM) based on image features extracted from T1-weighted and diffusion-weighted magnetic resonance images, respectively. Spatial normative models of image features were utilized to quantify neuroanatomical impairments in patients, which were then used to estimate the contributions of image features to brain age measures. For PAD of GM (GM-PAD), patients with MSA had significantly older brain age (9.33 years) than those with PD (0.75 years; P = 0.002) and HC (-1.47 years; P < 0.001), and no significant difference was found between PD and HC (P = 1.000). For PAD of WM (WM-PAD), it was significantly greater in MSA (9.27 years) than that in PD (1.90 years; P = 0.037) and HC (-0.74 years; P < 0.001); there was no significant difference between PD and HC (P = 0.087). The most salient image features that contributed to PAD in MSA and PD were different. For GM, they were the orbitofrontal regions and the cuneus in MSA and PD, respectively, and for WM, they were the central corpus callosum and the uncinate fasciculus in MSA and PD, respectively. Our results demonstrated that MSA revealed significantly greater PAD than PD, which might be related to markedly different neuroanatomical contributions to brain aging. The image features with distinct contributions to brain aging might be of value in the differential diagnosis of MSA and PD.

The Discovery of α-Synuclein in Lewy Pathology of Parkinson's Disease: The Inspiration of a Revolution.

Multiple system atrophy (MSA) is a neurodegenerative disease that belongs to the α synucleinopathies. Clinically, there is an overlap between MSA and Parkinson's disease (PD), especially at the early disease stage. However, these two pathologies differ in terms of disease progression. Currently, no biomarker exists to differentiate MSA from PD. MicroRNAs are non-coding RNAs implicated in gene expression regulation. MiRNAs modulate cellular activity and they control a range of physiological and pathological functions. miRNAs are found in biofluids, such as blood, serum, plasma, saliva, and cerebrospinal fluid. Many groups, including ours, found that circulating miRNAs are differently expressed in blood, plasma, serum and cerebrospinal fluid of PD and MSA patients. In the present study, our primary aim was to determine if serum mir-30-5p and mir-148b-5p can be used as biomarkers for early diagnosis of PD and/or MSA. Our secondary goal was to determine if serum levels of those miRNAs can be correlated with the patients' clinical profile. Using quantitative PCR (qPCR), we evaluated expression levels of miR-30c-5p and miR148b-5p in serum samples from PD (n = 56), MSA (n = 49), and healthy control (n = 50) subjects. We have found that miR-30c-5p is significantly upregulated in MSA if compared with PD and healthy control subjects. Moreover, serum miR-30c-5p levels correlate with disease duration in both MSA and PD. No significant difference was found in miR-148b-5p among MSA, PD and healthy control subjects. Our results suggest a possible role of serum miR-30-5p as a biomarker for diagnosis and progression of MSA.

Aggregation of alpha-synuclein (α-syn) is considered to be the major pathological hallmark and driving force of Multiple System Atrophy (MSA) and Parkinson's disease (PD). Immune dysfunctions have been associated with both MSA and PD and recently we reported that the levels of natural occurring autoantibodies (NAbs) with high-affinity/avidity toward α-synuclein are reduced in MSA and PD patients. Here, we aimed to evaluate the plasma immunoglobulin (Ig) composition binding α-syn and other amyloidogenic neuropathological proteins, and to correlate them with disease severity and duration in MSA and PD patients. All participants were recruited from a single neurological unit and the plasma samples were stored for later research at the Bispebjerg Movement Disorder Biobank. All patients were diagnosed according to current consensus criteria. Using multiple variable linear regression analyses, we observed higher levels of anti-α-syn IgG1 and IgG3 NAbs in MSA vs. PD, higher levels of anti-α-syn IgG2 NAbs in PD compared to controls, whereas anti-α-syn IgG4 NAbs were reduced in PD compared to MSA and controls. Anti-α-syn IgM levels were decreased in both MSA and PD. Further our data supported that MSA patients' immune system was affected with reduced IgG1 and IgM global levels compared to PD and controls, with further reduced global IgG2 levels compared to PD. These results suggest distinct autoimmune patterns in MSA and PD. These findings suggest a specific autoimmune physiological mechanism involving responses toward α-syn, differing in neurodegenerative disease with overlapping α-syn pathology.

Synucleinopathies [Parkinson's disease with or without dementia, dementia with Lewy bodies and multiple system atrophy] are neurodegenerative diseases that are defined by the presence of filamentous α-synuclein inclusions. We investigated the ability of luminescent conjugated oligothiophenes to stain the inclusions of Parkinson's disease and multiple system atrophy. They stained the Lewy pathology of Parkinson's disease and the glial cytoplasmic inclusions of multiple system atrophy. Spectral analysis of HS-68-stained inclusions showed a red shift in multiple system atrophy, but the difference with Parkinson's disease was not significant. However, when inclusions were double-labelled for HS-68 and an antibody specific for α-synuclein phosphorylated at S129, they could be distinguished based on colour shifts with blue designated for Parkinson's disease and red for multiple system atrophy. The inclusions of Parkinson's disease and multiple system atrophy could also be distinguished using fluorescence lifetime imaging. These findings are consistent with the presence of distinct conformers of assembled α-synuclein in Parkinson's disease and multiple system atrophy.

BackgroundNeuroinflammation is a process occurring in neurodegenerative diseases, such as Alzheimer’s Disease (AD) and parkinsonian syndromes. In light of emerging disease modifying trials, objective biomarkers are urgently needed. Here, we target reactive astrogliosis for biomarker development in a pilot cohort of Multiple System Atrophy (MSA), in which key pathology and associated neuroinflammation are regionally more restricted than in AD, but more pronounced than in Parkinson’s Disease (PD). We combine glial fibrillary acidic protein (GFAP) as fluid‐based biomarker with [18F]D2‐Deprenyl‐(DED)‐PET imaging, a novel PET tracer targeting MAO‐B, for comprehensive characterization of reactive astrogliosis in this model disease.MethodGFAP levels were analyzed in plasma samples of 23 MSA and 22 PD patients, as well as in CSF samples of 14 MSA and 14 PD patients. In a subset of patients (4 MSA‐P, 7 MSA‐C and 3 PD), first‐in‐human [18F]DED‐PET imaging was performed. Fluid‐based and PET‐imaging biomarker levels were cross‐sectionally compared, followed by correlation to clinical disease severity as indicated by UMSARS (Unified Multiple System Atrophy Rating Scale) and MDS‐UPDRS (MDS Unified Parkinson’s Disease Rating Scale). Correlation between fluid‐based biomarkers and PET imaging signals was performed. Two additional patients were on rasagiline treatment and proved target engagement of [18F]DED‐PET imaging.Result[18F]DED‐PET imaging showed significantly higher SUVr signals in various regions of MSA when compared to PD. Signal increases were seen in phenotype‐specific target regions with higher putaminal tracer binding in MSA‐P and higher cerebellar tracer binding in MSA‐C patients (Fig. 1). Decreased [18F]DED‐PET tracer signal was detected in patients on rasagiline treatment, indicating sufficient blocking (Fig. 2). While CSF and plasma GFAP levels did not differ between MSA and PD, GFAP levels in both biofluids correlated with disease severity in MSA (p &lt; 0.05), but not in PD.ConclusionWe present first‐in‐human data on a novel PET tracer to detect reactive astrogliosis in MSA. While [18F]DED‐PET imaging identifies disease‐ and entity‐specific regional astrogliosis, fluid biomarkers representing the overall level of astrogliosis appear to reflect clinical disease burden. Translation of these biomarkers into other neurodegenerative diseases, such as AD, should be pursued.

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by neuronal loss and gliosis, with oligodendroglial cytoplasmic inclusions (GCIs) containing α-synuclein being the primary pathological hallmark. Clinical presentations of MSA overlap with other parkinsonian disorders, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP), posing challenges in early diagnosis. Numerous studies have reported alterations in DNA methylation in neurodegenerative diseases, with candidate loci being identified in various parkinsonian disorders including MSA, PD, and PSP. Although MSA and PSP present with substantial white matter pathology, alterations in white matter have also been reported in PD. However, studies comparing the DNA methylation architectures of white matter in these diseases are lacking. We therefore aimed to investigate genome-wide DNA methylation patterns in the frontal lobe white matter of individuals with MSA (n = 17), PD (n = 17), and PSP (n = 16) along with controls (n = 15) using the Illumina EPIC array, to identify shared and disease-specific DNA methylation alterations. Genome-wide DNA methylation profiling of frontal lobe white matter in the three parkinsonian disorders revealed substantial commonalities in DNA methylation alterations in MSA, PD, and PSP. We further used weighted gene correlation network analysis to identify disease-associated co-methylation signatures and identified dysregulation in processes relating to Wnt signaling, signal transduction, endoplasmic reticulum stress, mitochondrial processes, RNA interference, and endosomal transport to be shared between these parkinsonian disorders. Our overall analysis points toward more similarities in DNA methylation patterns between MSA and PD, both synucleinopathies, compared to that between MSA and PD with PSP, which is a tauopathy. Our results also highlight several shared DNA methylation changes and pathways indicative of converging molecular mechanisms in the white matter contributing toward neurodegeneration in all three parkinsonian disorders.

While multiple system atrophy (MSA) has been considered a sporadic disease, there were previously reported multiplex families with MSA. Furthermore, several families with multiple patients with MSA and Parkinson's disease (PD) have been reported. As genetic risk factors for MSA, functionally impaired variants in COQ2 and Gaucher-disease-causing GBA variants have been reported. While it has been established that GBA variants are associated with PD, COQ2 may also be associated with PD. In 672 patients with MSA, we identified 12 multiplex families of patients with MSA and PD in first-degree relatives. We conducted a detailed analysis of the clinical presentations of these patients and genetic analyses of GBA and COQ2. In the multiplex families, a patient with MSA with predominant parkinsonism (MSA-P) was observed in nine families, while a patient with MSA cerebellar subtype (MSA-C) was observed in three families. Six families had siblings with MSA and PD, five families had a parent-offspring pair with MSA and PD, and in one family, a sibling and a parent of an MSA patient had PD. In genetic analyses of these patients, GBA variants were identified in one of the 12 MSA patients and two of the seven PD patients. Functionally impaired variants of COQ2 were identified in two of the 12 MSA patients and not identified in the seven PD patients. This study further emphasizes the occurrence of MSA and PD in first-degree relatives, raising the possibility that a common genetic basis underlies MSA and PD. Even though variants of COQ2 and GBA were identified in some patients in multiplex families with MSA and PD, it is necessary to further explore as yet unidentified genetic risk factors shared by MSA and PD.

Parkinson's disease (PD) and multiple system atrophy (MSA) show overlapping clinical features, posing diagnostic challenges. This study investigates whether distinct patterns of glymphatic dysfunction and free water (FW) accumulation can differentiate their underlying mechanisms and serve as discriminatory biomarkers. The objective of this study was to evaluate glymphatic function and FW pathology in PD and MSA, and to develop an integrated biomarker panel for differential diagnosis. We conducted a cross-sectional and longitudinal neuroimaging study involving 231 participants: 74 healthy control subjects (HCs), 79 patients with PD, and 78 patients with MSA. Glymphatic function (diffusion tensor image analysis along the perivascular space [DTI-ALPS] index and choroid plexus volume [CPV]) and FW distribution were derived from magnetic resonance imaging. Diagnostic performance was evaluated using receiver operating characteristic curves. Mediation analyses explored relationships among glymphatic impairment, FW accumulation, and clinical symptoms. Both PD and MSA showed reduced DTI-ALPS and enlarged CPV versus HC. FW accumulation exhibited disease-specific patterns: cortical/midline in PD and cerebellar in MSA. Longitudinal analysis confirmed progressive FW accumulation in these regions. Spatial coupling between glymphatic dysfunction and FW was strong in PD but absent in MSA. FW mediated the relationship between glymphatic impairment and motor/autonomic symptoms in PD, but not MSA. The integrated model combining neuroimaging and clinical metrics showed excellent discriminatory power for PD and MSA (area under the curve = 0.994). PD and MSA exhibit distinct glymphatic-FW pathological profiles. The coupled mechanism in PD contrasts with the uncoupled pathology in MSA, reflecting divergent pathogenesis. Multimodal imaging biomarkers demonstrate high diagnostic accuracy, showing strong potential for differential diagnosis in clinical practice. © 2026 International Parkinson and Movement Disorder Society.

JOURNAL/nrgr/04.03/01300535-202512000-00025/figure1/v/2025-01-31T122243Z/r/image-tiff In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell-free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson's disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson's disease (stage 1-2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls ( P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter ( P = 0.003 for Parkinson's disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson's disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54-24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55-122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease (OR: 0.16; 95% CI: 0.04-0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01-0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.

Multiple system atrophy (MSA) is a rare, rapidly-progressive neurodegenerative disorder, neuropathologically characterized by oligodendroglial α-synuclein aggregates.1 While in Parkinson's disease (PD), a neuronal α-synucleinopathy, both monogenic forms and a polygenic risk profile are known,2 MSA is generally considered a sporadic disorder.1 A family history (FH) for parkinsonism or other neurodegenerative disorders may in fact occur in people with MSA, but the contribution of genetic factors to MSA pathogenesis is not fully understood to date.3, 4 Here we retrospectively assessed the frequency rates of FH for parkinsonism, dementia, tremor, ataxia, or motor neuron disease within first-to-third-degree relatives of people included in the Innsbruck MSA Registry (n = 144), and compared them with historical MSA cohorts (cumulative n = 1173), Innsbruck-based PD cases (n = 226), and published population-based controls (cumulative n = 20,784). A detailed methodological description is provided in Supplementary Document 1. Forty-five MSA cases (40%) had a positive FH for neurodegenerative disorders, with parkinsonism being most prevalent (n = 26, 18%). FH rates mostly matched or exceeded those of historical MSA cohorts (Fig. 1A). The cumulative first-to-third-degree FH rates for neurodegenerative disorders and familial clustering (ie, ≥2 affected relatives) remained comparable between the MSA and PD cohort (Fig. 1B). Compared to pooled population-based controls, first-degree FH rates for dementia were significantly lower in both the MSA and PD cohorts, whereas the rate of first-degree FH for parkinsonism in MSA cases (10%, 95% CI 6–17) was between that of PD (17%, 95% CI 13–23; P = 0.079) and population-based controls (6%, 95% CI 5–6; P = 0.012; Fig. 1C and Supplementary Document 2). The ultimate mechanisms underlying MSA pathogenesis remain largely unknown.1, 5 The high frequency of FH for parkinsonism in people with MSA, close to that of PD and exceeding the one observed in population-based elderly controls, supports the contention that multiple, yet unidentified genetic variants might contribute to MSA pathogenesis. It also suggests a shared genetic susceptibility to the development of MSA and PD. Our study has limitations. FH history was collected retrospectively, carrying the risk for a documentation bias, and with the FH method, which obtains information on FH exclusively from patients and may both under- and overestimate FH rates.6 In the age of genomic medicine, however, FH still represents a valuable tool to assess the heritability of a given disorder, especially if genetic methods fail to disclose a causal relation. Non-neurodegenerative causes of tremor, dementia, or parkinsonism were also not systematically excluded in the relatives of our patients; genetic testing was available in a small percentage of patients only; and neuropathological confirmation in none. We also did not include an age- and sex-matched control group, but compared our data with the cumulative results of historical MSA cohorts and large population-based studies in aging individuals. Similar to PD, genetic susceptibility variants — if discovered for MSA — may be exploited for identifying persons at risk of developing the disease or in very early stages thereof, when putative neuroprotective strategies should ideally be most effective.7 Understanding the genetic underpinnings of the MSA pathological cascade might ultimately point out new therapeutic targets for this currently untreatable condition. Academic study without external funding. Dr Leys was supported by the Stichting ParkinsonFonds, US MSA Coalition and Dr Johannes & Hertha Tuba Foundation. Due to its retrospective nature and initiation before July 2020, neither written informed consent nor ethic approval was required for the present study. This study was conducted in accordance with the Declaration of Helsinki and the current European Data Protection Regulation. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The first and last named authors take full responsibility for the integrity of the data and the accuracy of the data analysis. The data supporting the findings of this study are available upon reasonable request from any qualified investigator. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. F.L.: 1B, 1C, 2B, 3A S.E.: 1C, 2C, 3B N.C.: 1C, 2C, 3B P.M.: 1A, 1C, 2C, 3B M.P.: 1C, 2C, 3B G.G.: 1A, 2A, 2C, 3B V.S.: 1A, 2C, 3B R.G.: 1A, 2C, 3B V.B.: 1A, 2C, 3B J.Z.: 1A, 2C, 3B S.K.: 1A, 2C, 3B W.P.: 1A, 2C, 3B K.S.: 1A, 2C, 3B G.K.W.: 1A, 2C, 3B A.F.: 1A, 1B, 1C, 2A, 2C, 3B F.L., S.E., N.C., P.M., M.P., G.G., V.S., R.G.: none. V.B.: receives research grants from the Stichting ParkinsonFonds and from Alzheimer Nederland (The Netherlands); honoraria from the International Parkinson and Movement Disorder Society, as Chair of the Congress Scientific Program Committee 2019–2021; and from Elsevier Ltd, as Co-Editor-in-Chief of Parkinsonism & Related Disorders, outside of the submitted work. J.Z.: none. S.K.: reports support from the Austrian Research Promotion Agency FFG, outside of the submitted work. W.P.: reports receiving personal fees from AbbVie, AFFiRiS, AstraZeneca, BIAL, Boston Scientific, Britannia, Intec, Ipsen, Lundbeck, NeuroDerm, Neurocrine, Denali Pharmaceuticals, Novartis, Orion Pharma, Prexton, Teva, UCB, and Zambon. He receives royalties from Thieme, Wiley Blackwell, Oxford University Press, and Cambridge University Press and grant support from The Michael J. Fox Foundation, EU FP7, and Horizon 2020, outside of the submitted work. K.S.: reports personal fees from Teva, UCB, Lundbeck, AOP Orphan Pharmaceuticals AG, Roche, Grünenthal, Stada, Licher Pharma, Biogen, BIAL, and Abbvie; honoraria from the International Parkinson and Movement Disorders Society; research grants from FWF Austrian Science Fund, The Michael J. Fox Foundation, and AOP Orphan Pharmaceuticals AG, outside the submitted work. G.K.W.: reports consultancy and lecture fees from AbbVie, AFFiRiS AG, AstraZeneca, Biogen, Biohaven, Inhibicase, Lundbeck, Merz, Ono, Teva, and Theravance, and research grants from the Austrian Science Fund (FWF), the Austrian National Bank, the US MSA Coalition, Parkinson Fonds Austria, the Dr Johannes und Hertha Tuba Foundation, and the International Parkinson and Movement Disorder Society, outside of the submitted work. A.F.: reports royalties from Springer Verlag, speaker fees and honoraria from Impact Medicom, Theravance Biopharma, AbbVie, the International Parkinson Disease and Movement Disorders Society, the Austrian Neurology Society, the Austrian Autonomic Society, and research grants from the Parkinson Fond, the US MSA Coalition, the Dr Johannes and Hertha Tuba Foundation, and the Austrian Exchange Program, outside of the submitted work. The data supporting the findings of this study are available upon reasonable request from any qualified investigator. Appendix S1. Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

MicroRNAs are reportedly involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy. We previously identified 7 differentially expressed microRNAs in Parkinson's disease patients and control sera (miR-30c, miR-31, miR-141, miR-146b-5p, miR-181c, miR-214, and miR-193a-3p). To investigate the expression levels of the 7 serum microRNAs in Parkinson's disease and multiple system atrophy, 23 early Parkinson's disease patients (who did not take any anti- Parkinson's disease drugs), 23 multiple system atrophy patients, and 24 normal controls were recruited at outpatient visits in this study. The expression levels of the 7 microRNAs in serum were detected using quantitative real-time polymerase chain reaction. A receiver operating characteristic curve was used to evaluate whether microRNAs can differentially diagnose Parkinson's disease and multiple system atrophy. Clinical scales were used to analyze the correlations between serum microRNAs and clinical features. The results indicated that miR-214 could distinguish Parkinson's disease from the controls, and another 3 microRNAs could differentiate multiple system atrophy from the controls (miR-141, miR-193a-3p, and miR-30c). The expression of miR-31, miR-141, miR-181c, miR-193a-3p, and miR-214 were lower in multiple system atrophy than in Parkinson's disease (all P < 0.05). Combinations of microRNAs accurately discriminated Parkinson's disease from multiple system atrophy (area under the receiver operating characteristic curve = 0.951). For the correlation analysis, negative correlations were discovered between the expression of miR-214 and the Hamilton Anxiety Scale and Parkinson's Disease Non-Motor Symptom scores (all P < 0.05). Our results demonstrate that the distinctive characteristics of microRNAs differentiate Parkinson's disease and multiple system atrophy patients from healthy controls and may be used for the early diagnosis of Parkinson's disease and multiple system atrophy.

Objective To evaluate the apparant diffusion coefficient (ADC) values of cerebellar and the middle cerebellar peduncles in the differential diagnosis of multiple system atrophy (MSA) and Parkinson disease (PD). Methods Conventional MRI and DWI were performed in 18 clinically proved MSA patients with 7 cases of early cases (early-stage MSA group), 19 PD patients (PD group) and 18 agematched normal controls (the control group). DWI was performed using a single shot-spin echo-echo planar imaging sequences, and ADC values were measured in the ROIs (0. 16 cm2) of the bilateral cerebellum, the middle cerebellar peduncles and cerebral white matter. Then one way ANOVA test was used for statistical analysis. Results Of the 18 MSA patients, 11 had MR abnormalities, 8 had hot-cross bun sign in the pens on T2-weighted images, 11 patients had pontine, cerebellar and medulla oblongata atrophy, 10 patients had atrophy of the middle cerebellar peduncles, 2 patients had hyperintense rim of the putamen and putaminal atrophy on T2-weighted images. The ADC values in the middle cerebellar peduncles were significantly increased in the MSA group[ (0. 98 ±0. 07) × 103 mm2/s] and early-stnge MSA group [ (0. 95 ±0. 05) ×103 mm2/s] as compared to PD group [ (0. 77 ±0. 04) × 103 mm2/s] and control group[ (0. 78 ±0. 04) ×103 mm2/s]. There was statistical significant difference among them (F = 91.049,55. 301, P ＜ 0.01 ).There was no overlap in the distribution of ADC values of the middle cerebellar peduncles among the MSA group [ (0.86-1.13 ) × 103 mm2/s ], early-stage MSA group [ (0. 86-1.02 ) × 103 mm2/s ] and PD group [ (0. 68-0. 84) × 103 mm2/s] and the control group [ (0. 69-0. 82) × 103 mm2/s]. The ADC values in the cerebellum were significantly increased in the MSA group[ (0. 95 ±0. 09) × 103 mm2/s] and early-stage MSA group [ (0. 92 ±0. 07) × 103 mm2/s] as compared to PD group [ (0. 78 ±0. 05) × 103 mm2/s] and control group[ (0. 79 ± 0. 05 ) × 103 mm2/s ]. Statistically significant difference was found among them (F =39. 274,18. 623 ,P ＜0. 01 ). There was overlap in the distribution of ADC values of the cerebellum [ MSAgroup(0. 80-1.10) × 103 mm2/s,early stage MSA group (0. 80-0. 99) × 103 mm2/s,PD group(0. 72-0. 90) × 103 mm2/s,control group (0. 71-0. 87) × 103 mm2/s]. There was no significant difference among the ADC values of MSA group, MSA group(early stages) and PD group and the control group in the cerebral white matter( P ＞ 0. 05 ). Conclusions ADC values in the cerebellum and the middle cerebellar peduncles have very important significance in differential diagnosis between MSA and PD. Key words: Multiple system atrophy; Parkinson disease; Diffusion magnetic resonance imaging

OBJECTIVESUrinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders....