Multiple system atrophy of the cerebellar type: clinical state of the art

Mov Disord. 2014 Mar;29(3):294-304. doi: 10.1002/mds.25847. Epub 2014 Feb 24.


Multiple system atrophy (MSA) is a late-onset, sporadic neurodegenerative disorder clinically characterized by autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. It is neuropathologically defined by widespread and abundant central nervous system α-synuclein-positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. There are two clinical subtypes of MSA distinguished by the predominant motor features: the parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). Despite recent progress in understanding the pathobiology of MSA, investigations into the symptomatology and natural history of the cerebellar variant of the disease have been limited. MSA-C presents a unique challenge to both clinicians and researchers alike. A key question is how to distinguish early in the disease course between MSA-C and other causes of adult-onset cerebellar ataxia. This is a particularly difficult question, because the clinical framework for conceptualizing and studying sporadic adult-onset ataxias continues to undergo flux. To date, several investigations have attempted to identify clinical features, imaging, and other biomarkers that may be predictive of MSA-C. This review presents a clinically oriented overview of our current understanding of MSA-C with a focus on evidence for distinguishing MSA-C from other sporadic, adult-onset ataxias.

Keywords: ataxia; cerebellum; idiopathic late-onset cerebellar ataxia; multiple system atrophy; sporadic adult-onset ataxia of unknown etiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cerebellar Ataxia / metabolism
  • Cerebellum / metabolism*
  • Disease Models, Animal
  • Humans
  • Multiple System Atrophy / metabolism*
  • Multiple System Atrophy / therapy
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / therapy
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein