Ling, Helen (24781067400)Helen (24781067400)LingAsi, Yasmine T. (54885244600)Yasmine T. (54885244600)AsiPetrovic, Igor N. (7004083314)Igor N. (7004083314)PetrovicAhmed, Zeshan (14009978300)Zeshan (14009978300)AhmedPrashanth, L.K. (55330727200)L.K. (55330727200)PrashanthHazrati, Lili-Naz (57204409408)Lili-Naz (57204409408)HazratiNishizawa, Masatoyo (7202978752)Masatoyo (7202978752)NishizawaOzawa, Tetsutaro (7402329701)Tetsutaro (7402329701)OzawaLang, Anthony (36042140400)Anthony (36042140400)LangLees, Andrew J. (57208252964)Andrew J. (57208252964)LeesRevesz, Tamas (7102381695)Tamas (7102381695)ReveszHolton, Janice L. (7101772051)Janice L. (7101772051)Holton2025-07-022025-07-022015https://doi.org/10.1002/mds.26220https://www.scopus.com/inward/record.uri?eid=2-s2.0-84931958006&doi=10.1002%2fmds.26220&partnerID=40&md5=e283dffbd2ce2a5af411c66941ce148bhttps://remedy.med.bg.ac.rs/handle/123456789/13506Background: 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.Alpha-synucleinMinimal changeMultiple system atrophySudden unexpected death