TY - JOUR
T1 - Multiple System Atrophy Without Dysautonomia
T2 - An Autopsy-Confirmed Study
AU - Wilkens, Ida
AU - Bebermeier, Sarah
AU - Heine, Johanne
AU - Ruf, Viktoria Constanze
AU - Compta, Yaroslau
AU - Molina Porcel, Laura
AU - Troakes, Claire
AU - Vamanu, Albert
AU - Downes, Sophia
AU - Irwin, David John
AU - Cohen, Jesse
AU - Lee, Edward B.
AU - Nilsson, Christer F.
AU - Englund, Elisabet M.
AU - Nemati, Mojtaba
AU - Katzdobler, Sabrina
AU - Levin, Johannes
AU - Bernhardt, Alexander Maximilian
AU - Pantelyat, Alexander
AU - Seemiller, Joseph
AU - Berger, Stephen
AU - Van Swieten, John C.
AU - Dopper, Elise G.P.
AU - Rozemuller, Annemieke J.M.
AU - Kovacs, Gabor G.
AU - Bendahan, Nathaniel
AU - Lang, Anthony E.
AU - Herms, Jochen
AU - Höglinger, Günter U.
AU - Hopfner, Franziska
PY - 2025/12/9
Y1 - 2025/12/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105021797041
U2 - 10.1212/WNL.0000000000214316
DO - 10.1212/WNL.0000000000214316
M3 - Article
C2 - 41232058
AN - SCOPUS:105021797041
SN - 0028-3878
VL - 105
SP - 1
EP - 8
JO - Neurology
JF - Neurology
IS - 11
M1 - e214316
ER -