{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:42:42Z","timestamp":1792478562678,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Multiple System Atrophy Trust and National Institute for Health Research University College London Hospitals Biomedical Research Centre"},{"name":"CBD solutions"},{"name":"Kuwait Ministry of Higher Education"},{"name":"Reta Lila Weston Institute for Neurological studies"},{"name":"Michael J Fox Foundation and Parkinson's UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Glial cytoplasmic inclusions containing \u03b1\u2010synuclein are the pathological hallmark of multiple system atrophy (MSA). Minimal change (MC\u2010MSA) is an unusual MSA subtype with neuronal loss largely restricted to the substantia nigra and locus coeruleus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry on selected brain regions and semiquantitative assessment were performed on six MC\u2010MSA and eight MSA control cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>More neuronal cytoplasmic inclusions were seen in the caudate and substantia nigra in MC\u2010MSA than in MSA controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.002), without any statistical difference in glial cytoplasmic inclusion load in any region. Severe glial cytoplasmic inclusion load was found in the ventrolateral medulla (<jats:italic>P<\/jats:italic>\u2009=\u20091.0) and nucleus raphe obscurus (<jats:italic>P<\/jats:italic>\u2009=\u20090.4) in both groups. When compared with MSA controls, the three MC\u2010MSA cases who had died of sudden unexpected death had an earlier age of onset (mean: 38 vs. 57.6 y, <jats:italic>P<\/jats:italic>\u2009=\u20090.02), a numerically shorter disease duration (mean: 5.3 vs. 8 y, <jats:italic>P<\/jats:italic>\u2009=\u20090.2) 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\u2010MSA 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 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) 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\u2010MSA cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings could suggest that \u03b1\u2010synuclein\u2013associated oligodendroglial pathology may lead to neuronal dysfunction sufficient to cause clinical symptoms before overt neuronal loss in MSA. \u00a9 2015 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26220","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T12:46:12Z","timestamp":1428497172000},"page":"960-967","source":"Crossref","is-referenced-by-count":53,"title":["Minimal change multiple system atrophy: An aggressive variant?"],"prefix":"10.1002","volume":"30","author":[{"given":"Helen","family":"Ling","sequence":"first","affiliation":[{"name":"Queen Square Brain Bank, Department of Molecular Neuroscience UCL Institute of Neurology  UK"},{"name":"Reta Lila Weston Institute of Neurological Studies UCL Institute of Neurology London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine T.","family":"Asi","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank, Department of Molecular Neuroscience UCL Institute of Neurology  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor N.","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Reta Lila Weston Institute of Neurological Studies UCL Institute of Neurology London UK"},{"name":"Institute of Neurology School of Medicine  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeshan","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank, Department of Molecular Neuroscience UCL Institute of Neurology  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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