Multiple system atrophy

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease (one of the synucleinopathies) characterized by varying degrees of cerebellar ataxia, autonomic dysfunction, parkinsonism, and corticospinal dysfunction. 

Multiple systemic atrophy is a sporadic disease, with a prevalence of 4 per 100,000 2. Typically symptoms begin between 40 and 60 years of age 2

Clinical presentation is variable, but typically presents in one of three patterns (initially described as separate entities) 1,2:

In a 2007 consensus paper 6 MSA has been divided clinically into two forms according to the dominant non-autonomic symptoms: 

  1. MSA-C: predominance of cerebellar symptoms (olivopontocerebellar atrophy)
  2. MSA-P: predominance of parkinsonian signs and symptoms (striatonigral degeneration)

Some older texts refer to MSA-A to denote Shy-Drager syndrome. In the latest consensus however autonomic symptoms are considered part of both MSA-C and MSA-P and thus the term MSA-A is no longer used.

Like other synucleinopathies, multiple systemic atrophy results from abnormalities of alpha-synuclein metabolism, resulting in intracellular deposition. Unlike Parkinson disease and Lewy body dementia (two other synucleinopathies) these intracellular deposits are found not only in neurons but also in oligodendroglia 2

MRI is the modality of choice for imaging patients with suspected multiple system atrophy (MSA).

  • T2: hyperintensities typically present in the pontocerebellar tracts
  • putaminal findings in MSA-P 5:
    • reduced volume
    • reduced GRE and T2 signal relative to globus pallidus
    • reduced GRE and T2 signal relative to the red nucleus
    • abnormally high T2 linear rim surrounding the putamen (putaminal rim sign), seen at 1.5 T (this is normal at 3 T) 7 (see case 3)
  • MSA-C
    • disproportionate atrophy of the cerebellum and brainstem (especially olivary nuclei and middle cerebellar peduncle)
  • ADC values: higher in the pons, cerebellum, and putamen than in Parkinson disease or controls
  • fractional anisotropy (FA): lower in the pons, cerebellum, and putamen than in Parkinson disease or controls

On SPECT/CT with I-123 ioflupane, there is loss of the normal comma- or crescent-shaped tracer uptake in the striatum. Instead, a period- or oval-shaped uptake is seen within the caudate nucleus head without tracer uptake in the putamen. Quantitative assessment reveals reduced uptake in the putamen compared to norms.

Unfortunately, no effective treatment is currently available. The disease progresses relentlessly culminating in death usually within 10 years of diagnosis 2

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

Article information

rID: 7271
Section: Syndromes
Synonyms or Alternate Spellings:
  • Multisystem atrophy
  • Multisystem atrophy
  • Multiple system atrophy (MSA)
  • MSA
  • Multiple systemic atrophy
  • Multiple systemic atrophy (MSA)

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Cases and figures

  • Case 1
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  • Case 2: with hot cross bun sign
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  • Case 3: MSA-P bright putaminal rim sign
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  • Case 4: MSA-C
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  • Case 5
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  • Case 6
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  • Case 7
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  • Case 8
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  • Case 9
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  • Case 10
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