Minimal change multiple system atrophy: an aggressive variant?

Mov Disord. 2015 Jun;30(7):960-7. doi: 10.1002/mds.26220. Epub 2015 Apr 8.


Background: Glial cytoplasmic inclusions containing α-synuclein are the pathological hallmark of multiple system atrophy (MSA). Minimal change (MC-MSA) is an unusual MSA subtype with neuronal loss largely restricted to the substantia nigra and locus coeruleus.

Methods: Immunohistochemistry on selected brain regions and semiquantitative assessment were performed on six MC-MSA and eight MSA control cases.

Results: More neuronal cytoplasmic inclusions were seen in the caudate and substantia nigra in MC-MSA than in MSA controls (P = 0.002), without any statistical difference in glial cytoplasmic inclusion load in any region. Severe glial cytoplasmic inclusion load was found in the ventrolateral medulla (P = 1.0) and nucleus raphe obscurus (P = 0.4) in both groups. When compared with MSA controls, the three MC-MSA cases who had died of sudden unexpected death had an earlier age of onset (mean: 38 vs. 57.6 y, P = 0.02), a numerically shorter disease duration (mean: 5.3 vs. 8 y, P = 0.2) and a more rapid clinical progression with most of the clinical milestones reached within 3 y of presentation, suggesting an aggressive variant of MSA. Another three MC-MSA cases, who had died of unrelated concurrent diseases, had an age of onset (mean: 57.7 y) and temporal course similar to controls, had less severe neuronal loss and gliosis in the medial and dorsolateral substantia nigra subregions (P < 0.05) than in MSA controls, and could be considered as a unique group with interrupted pathological progression. Significant respiratory dysfunction and early orthostatic hypotension were observed in all MC-MSA cases.

Conclusions: Our findings could suggest that α-synuclein-associated oligodendroglial pathology may lead to neuronal dysfunction sufficient to cause clinical symptoms before overt neuronal loss in MSA. © 2015 International Parkinson and Movement Disorder Society.

Keywords: Minimal change; alpha-synuclein; multiple system atrophy; sudden unexpected death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Brain / metabolism
  • Brain / pathology*
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology*
  • Male
  • Middle Aged
  • Multiple System Atrophy / classification*
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / pathology*
  • Tissue Banks*
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein