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

Abstract

SummaryBackgroundMultiple 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.MethodsPatients 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.Findings141 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.InterpretationOur 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.FundingFifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.

Epidemiology of Multiple System Atrophy in Hokkaido, the Northernmost Island of Japan

“…This epidemiological difference has been confirmed by other studies in each region [6,7]. The difference between MSA-C and MSA-P is the rate of motor symptom progression [8].…”

Quantitative evaluation of gait ataxia by accelerometers

“…Sample size estimation showed that an interventional trial with 258 patients would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power [12].…”

Comparison of Different Symptom Assessment Scales for Multiple System Atrophy

“…The former groups were graded to have a rapid progression. The poor prognosis of MSA-P and rapid progression of early-stage MSA patients were previously mentioned [17,35], but it was not indicated that early-onset MSA would rapidly progress.…”

“…Thus, the progression of autonomic dysfunction may not be evaluated precisely. Autonomic dysfunction is a very important factor in MSA progression [17,43], but these SRMs were small. Existing scales could not capture accurate changes in autonomic dysfunction.…”

“…The UMSARS has been used in many clinical studies, such as the EMSA [17] and the North American MSA (NAMSA) study [18]. The UMSARS measures various symptoms of MSA and is very useful for total symptom assessments of MSA.…”