The natural history of multiple system atrophy: A prospective European cohort study

Gregor K. Wenning, Felix Geser, Florian Krismer, Klaus Seppi, Susanne Duerr, Sylvia Boesch, Martin Köllensperger, Georg Goebel, Karl P. Pfeiffer, Paolo Barone, Maria Teresa Pellecchia, Niall P. Quinn, Vasiliki Koukouni, Clare J. Fowler, Anette Schrag, Christopher J. Mathias, Nir Giladi, Tanya Gurevich, Erik Dupont, Karen OstergaardChrister F. Nilsson, Håkan Widner, Wolfgang Oertel, Karla Maria Eggert, Alberto Albanese, Francesca Del Sorbo, Eduardo Tolosa, Adriana Cardozo, Günther Deuschl, Helge Hellriegel, Thomas Klockgether, Richard Dodel, Cristina Sampaio, Miguel Coelho, Ruth Djaldetti, Eldad Melamed, Thomas Gasser, Christoph Kamm, Giuseppe Meco, Carlo Colosimo, Olivier Rascol, Wassilios G. Meissner, François Tison, Werner Poewe

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Abstract

Background: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1-11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09-3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02-4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5-0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1-10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Funding: Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.

Original languageEnglish
Pages (from-to)264-274
Number of pages11
JournalThe Lancet Neurology
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2013

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ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Wenning, G. K., Geser, F., Krismer, F., Seppi, K., Duerr, S., Boesch, S., Köllensperger, M., Goebel, G., Pfeiffer, K. P., Barone, P., Pellecchia, M. T., Quinn, N. P., Koukouni, V., Fowler, C. J., Schrag, A., Mathias, C. J., Giladi, N., Gurevich, T., Dupont, E., ... Poewe, W. (2013). The natural history of multiple system atrophy: A prospective European cohort study. The Lancet Neurology, 12(3), 264-274. https://doi.org/10.1016/S1474-4422(12)70327-7