title: Minimal change multiple system atrophy: an aggressive variant?
abstract: 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.
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.|Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors: Helen
authors: H
authors: Ling
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.
authors: Yasmine T
authors: YT
authors: Asi
authors: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.|Institute of Neurology, School of Medicine, Belgrade, Serbia.
authors: Igor N
authors: IN
authors: Petrovic
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.
authors: Zeshan
authors: Z
authors: Ahmed
authors: University of Toronto, Toronto, Canada.|Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada.
authors: L K
authors: LK
authors: Prashanth
authors: University of Toronto, Toronto, Canada.|Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada.
authors: Lili-Naz
authors: LN
authors: Hazrati
authors: Department of Neurology, Niigata University, Japan.
authors: Masatoyo
authors: M
authors: Nishizawa
authors: Department of Neurology, Niigata University, Japan.
authors: Tetsutaro
authors: T
authors: Ozawa
authors: University of Toronto, Toronto, Canada.|Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada.
authors: Anthony
authors: A
authors: Lang
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.|Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors: Andrew J
authors: AJ
authors: Lees
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.
authors: Tamas
authors: T
authors: Revesz
authors: Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UK.
authors: Janice L
authors: JL
authors: Holton
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000145:classification* / Q000378:metabolism / Q000473:pathology*; D014015:Tissue Banks; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Minimal change; alpha-synuclein; multiple system atrophy; sudden unexpected death