The natural history of multiple system atrophy: a prospective European cohort study
(2013) In Lancet Neurology 12(3). p.264-274- 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... (More)
- 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. (Less)
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- publishing date
- 2013
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- Contribution to journal
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- published
- subject
- in
- Lancet Neurology
- volume
- 12
- issue
- 3
- pages
- 264 - 274
- publisher
- Lancet Publishing Group
- external identifiers
-
- wos:000318531300012
- scopus:84876332892
- ISSN
- 1474-4465
- DOI
- 10.1016/S1474-4422(12)70327-7
- language
- English
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- yes
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- 2b833df1-35b2-4f5e-8fcd-c0b4c69e67b9 (old id 3839637)
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@article{2b833df1-35b2-4f5e-8fcd-c0b4c69e67b9,
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.}},
author = {{Wenning, Gregor K. and Geser, Felix and Krismer, Florian and Seppi, Klaus and Duerr, Susanne and Boesch, Sylvia and Koellensperger, Martin and Goebel, Georg and Pfeiffer, Karl P. and Barone, Paolo and Pellecchia, Maria Teresa and Quinn, Niall P. and Koukouni, Vasiliki and Fowler, Clare J. and Schrag, Anette and Mathias, Christopher J. and Giladi, Nir and Gurevich, Tanya and Dupont, Erik and Ostergaard, Karen and Nilsson, Christer and Widner, Håkan and Oertel, Wolfgang and Eggert, Karla Maria and Albanese, Alberto and del Sorbo, Francesca and Tolosa, Eduardo and Cardozo, Adriana and Deuschl, Guenther and Hellriegel, Helge and Klockgether, Thomas and Dodel, Richard and Sampaio, Cristina and Coelho, Miguel and Djaldetti, Ruth and Melamed, Eldad and Gasser, Thomas and Kamm, Christoph and Meco, Giuseppe and Colosimo, Carlo and Rascol, Olivier and Meissner, Wassilios G. and Tison, Francois and Poewe, Werner}},
issn = {{1474-4465}},
language = {{eng}},
number = {{3}},
pages = {{264--274}},
publisher = {{Lancet Publishing Group}},
series = {{Lancet Neurology}},
title = {{The natural history of multiple system atrophy: a prospective European cohort study}},
url = {{http://dx.doi.org/10.1016/S1474-4422(12)70327-7}},
doi = {{10.1016/S1474-4422(12)70327-7}},
volume = {{12}},
year = {{2013}},
}