Multiple System Atrophy Without Dysautonomia: An Autopsy-Confirmed Study.
| Title: | Multiple System Atrophy Without Dysautonomia: An Autopsy-Confirmed Study. |
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| Authors: | Wilkens I; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; Bebermeier S; Department of Pedagogic Psychology, Leibniz University Hannover, Germany.; Heine J; Department of Neurology, Hannover Medical School, Germany.; Ruf VC; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Germany.; Compta Y; Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, UBNeuro, Spain.; Molina Porcel L; Alzheimer's Disease and Other Cognitive Disorders Unit. Neurology Service, Institute of Neurosciences Hospital Clínic de Barcelona, FRCB/IDIBAPS, University of Barcelona, Spain.; Neurological Tissue Bank, Biobanc-Hospital Clínic-FRCB/IDIBAPS, Barcelona, Spain.; Troakes C; Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.; Vamanu A; Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.; Downes S; Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.; Irwin DJ; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia.; Cohen J; Department of Neurology, University of Florida, Jacksonville.; Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey.; Lee EB; Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia.; Nilsson CF; Division of Neurology, Department of Clinical Sciences, Lund University, Sweden.; Englund EM; Division of Pathology, Department of Clinical Sciences, Lund University, Sweden.; Nemati M; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; Katzdobler S; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; Levin J; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Germany.; Bernhardt AM; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; Pantelyat A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.; Seemiller J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.; Berger S; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.; Van Swieten JC; Department of Neurology, Erasmus Medical Centre, Rotterdam, the Netherlands.; Dopper EGP; Department of Neurology, Erasmus Medical Centre, Rotterdam, the Netherlands.; Rozemuller AJM; Department of Pathology, Amsterdam UMC, Amsterdam Neuroscience, the Netherlands.; Kovacs GG; Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada; and.; Edmond J. Safra Program in Parkinson's Disease and the Rossy Progressive Supranuclear Palsy Centre, Division of Neurology, Toronto Western Hospital, University Health Network and the University of Toronto, Ontario, Canada.; Bendahan N; Edmond J. Safra Program in Parkinson's Disease and the Rossy Progressive Supranuclear Palsy Centre, Division of Neurology, Toronto Western Hospital, University Health Network and the University of Toronto, Ontario, Canada.; Lang AE; Edmond J. Safra Program in Parkinson's Disease and the Rossy Progressive Supranuclear Palsy Centre, Division of Neurology, Toronto Western Hospital, University Health Network and the University of Toronto, Ontario, Canada.; Herms J; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Germany.; Höglinger GU; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Germany.; Hopfner F; Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany. |
| Source: | Neurology [Neurology] 2025 Dec 09; Vol. 105 (11), pp. e214316. Date of Electronic Publication: 2025 Nov 13. |
| Publication Type: | Journal Article; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0401060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1526-632X (Electronic) Linking ISSN: 00283878 NLM ISO Abbreviation: Neurology Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hagerstown, MD : Lippincott Williams & Wilkins; Original Publication: Minneapolis. |
| MeSH Terms: | Multiple System Atrophy*/pathology ; Multiple System Atrophy*/diagnosis ; Multiple System Atrophy*/physiopathology; Humans ; Female ; Male ; Middle Aged ; Aged ; Autopsy ; Primary Dysautonomias ; Disease Progression ; Cohort Studies ; Parkinsonian Disorders |
| Abstract: | Background and Objectives: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by 3 core symptom complexes: parkinsonism, cerebellar syndrome, and dysautonomia. Recent Movement Disorder Society (MDS) criteria allow for the clinical diagnosis of MSA based solely on motor symptoms, without requiring dysautonomia. This study aimed to evaluate the frequency and disease trajectory of MSA patients without dysautonomia compared with those with autonomic involvement.; Methods: A multicenter cohort of autopsy-confirmed patients with MSA was analyzed for demographic characteristics, symptom onset, and progression of parkinsonism, cerebellar syndrome, and dysautonomia. Clinical data were collected through standardized chart reviews across participating centers and categorized using the MDS-MSA criteria. Patients were grouped according to their initial symptom complex and tracked for the evolution of additional symptoms. Analyses included time to development of further symptom complexes, age at symptom onset, disease duration, and phenotype at the last recorded visit. Patients with motor symptoms only were matched to patients with similar demographics but with dysautonomia. Statistical methods included ANOVA, t tests, Welch t tests, and χ2 tests, with significance set at p < 0.05.; Results: Among 140 patients (mean age at onset 62.3 ± 8.9 years; 44% female), 81 (58%) initially presented without dysautonomia (57 with parkinsonism only, 17 with cerebellar syndrome only, 7 with both). At final follow-up, 12 patients (9%) had not developed dysautonomia. These patients showed significantly longer disease duration (mean 8.1 ± 2.1 years) than matched patients with dysautonomia (mean 6.3 ± 2.6 years; p = 0.035). Overall, 51% of patients developed all 3 symptom complexes. Patients with cerebellar onset progressed more rapidly to multisystem involvement than those with parkinsonian onset (mean interval to second symptom: 2.0 vs 3.4 years; p < 0.05).; Discussion: The MDS-MSA criteria expand the diagnostic scope by identifying a motor-only subgroup with a distinct and potentially slower disease course. These findings underscore the importance of including motor-only patients in natural history and interventional studies. Limitations include retrospective data collection and potential variability in symptom documentation. |
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| Grant Information: | T32 AG027668 United States AG NIA NIH HHS |
| Entry Date(s): | Date Created: 20251113 Date Completed: 20251113 Latest Revision: 20260507 |
| Update Code: | 20260507 |
| PubMed Central ID: | PMC12615010 |
| DOI: | 10.1212/WNL.0000000000214316 |
| PMID: | 41232058 |
| Database: | MEDLINE |
Journal Article; Multicenter Study