Journal Article

DZNE-2025-01268

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multiple System Atrophy Without Dysautonomia: An Autopsy-Confirmed Study.

Wilkens, I.Extern* ; Bebermeier, S. ; Heine, J. ; Ruf, V. C. ; Compta, Y. ; Molina Porcel, L. ; Troakes, C. ; Vamanu, A. ; Downes, S. ; Irwin, D. J. ; Cohen, J. ; Lee, E. B. ; Nilsson, C. F. ; Englund, E. M. ; Nemati, M.Extern* ; Katzdobler, S.Extern* ; Levin, J.DZNE* ; Bernhardt, A. M.Extern* ; Pantelyat, A. ; Seemiller, J. ; Berger, S. ; Van Swieten, J. C. ; Dopper, E. G. P. ; Rozemuller, A. J. M. ; Kovacs, G. G. ; Bendahan, N. ; Lang, A. E. ; Herms, J.DZNE* ; Höglinger, G. U.DZNE* ; Hopfner, F.Extern*

2025
Wolters Kluwer Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1212/WNL.0000000000214316

Abstract: 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.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.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).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.

Keyword(s): Humans (MeSH) ; Multiple System Atrophy: pathology (MeSH) ; Multiple System Atrophy: diagnosis (MeSH) ; Multiple System Atrophy: physiopathology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Aged (MeSH) ; Autopsy (MeSH) ; Primary Dysautonomias (MeSH) ; Disease Progression (MeSH) ; Cohort Studies (MeSH) ; Parkinsonian Disorders (MeSH)

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Clinical Neurodegeneration (AG Levin)
3. Translational Brain Research (AG Herms)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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