Minimal change multiple system atrophy: An aggressive variant?

Not PD, but great work nonetheless from my colleague Helen who has done so much towards unravelling clinico-pathological aspects of atypical Parkinson's disorders such as MSA, CBS and PSP. Understanding more about PD and atypical Parkinson's ultimately requires more patients to commit to brain donation...it is not a pleasant topic I know, but it does move understanding further forwards and the Queen Square Brain Bank has been instrumental in these advances...

Mov Disord. 2015 Apr 8. doi: 10.1002/mds.26220. [Epub ahead of print]

Ling H, Asi YT, Petrovic IN, Ahmed Z, Prashanth LK, Hazrati LN, Nishizawa M, Ozawa T, Lang A, Lees AJ, Revesz T, Holton JL.

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

The 'hot cross bun' sign above left is a typical imaging feature in MSA

(Image from physio-pedia.com)