title: The natural history of multiple system atrophy: a prospective European cohort study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. gregor.wenning@i-med.ac.at
authors: Gregor K
authors: GK
authors: Wenning
authors: Felix
authors: F
authors: Geser
authors: Florian
authors: F
authors: Krismer
authors: Klaus
authors: K
authors: Seppi
authors: Susanne
authors: S
authors: Duerr
authors: Sylvia
authors: S
authors: Boesch
authors: Martin
authors: M
authors: Köllensperger
authors: Georg
authors: G
authors: Goebel
authors: Karl P
authors: KP
authors: Pfeiffer
authors: Paolo
authors: P
authors: Barone
authors: Maria Teresa
authors: MT
authors: Pellecchia
authors: Niall P
authors: NP
authors: Quinn
authors: Vasiliki
authors: V
authors: Koukouni
authors: Clare J
authors: CJ
authors: Fowler
authors: Anette
authors: A
authors: Schrag
authors: Christopher J
authors: CJ
authors: Mathias
authors: Nir
authors: N
authors: Giladi
authors: Tanya
authors: T
authors: Gurevich
authors: Erik
authors: E
authors: Dupont
authors: Karen
authors: K
authors: Ostergaard
authors: Christer F
authors: CF
authors: Nilsson
authors: Håkan
authors: H
authors: Widner
authors: Wolfgang
authors: W
authors: Oertel
authors: Karla Maria
authors: KM
authors: Eggert
authors: Alberto
authors: A
authors: Albanese
authors: Francesca
authors: F
authors: del Sorbo
authors: Eduardo
authors: E
authors: Tolosa
authors: Adriana
authors: A
authors: Cardozo
authors: Günther
authors: G
authors: Deuschl
authors: Helge
authors: H
authors: Hellriegel
authors: Thomas
authors: T
authors: Klockgether
authors: Richard
authors: R
authors: Dodel
authors: Cristina
authors: C
authors: Sampaio
authors: Miguel
authors: M
authors: Coelho
authors: Ruth
authors: R
authors: Djaldetti
authors: Eldad
authors: E
authors: Melamed
authors: Thomas
authors: T
authors: Gasser
authors: Christoph
authors: C
authors: Kamm
authors: Giuseppe
authors: G
authors: Meco
authors: Carlo
authors: C
authors: Colosimo
authors: Olivier
authors: O
authors: Rascol
authors: Wassilios G
authors: WG
authors: Meissner
authors: François
authors: F
authors: Tison
authors: Werner
authors: W
authors: Poewe
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000145:classification / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D010300:Parkinson Disease / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D010641:Phenotype; D011446:Prospective Studies; D012720:Severity of Illness Index
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