Editing Multiple system atrophy (section)

=== Pathologic ===
Pathological diagnosis can only be made at autopsy by finding abundant [[glia]]l [[cytoplasm]]ic [[inclusion (cell)|inclusion]]s (GCIs) on histological specimens of the central nervous system.<ref name="pmid2559165">{{cite journal | vauthors = Papp MI, Kahn JE, Lantos PL | title = Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome) | journal = Journal of the Neurological Sciences | volume = 94 | issue = 1–3 | pages = 79–100 | date = December 1989 | pmid = 2559165 | doi = 10.1016/0022-510X(89)90219-0 | s2cid = 1199951 }}</ref>

''Olivopontocerebellar atrophy'' can be used as a pathological term to describe degeneration of neurons in specific areas of the brain – the [[cerebellum]], [[pons]], and [[inferior olivary nucleus]].<ref name=nidsopca>{{cite web |title=NINDS Olivopontocerebellar Atrophy Information Page |access-date=7 Feb 2012 |url=http://www.ninds.nih.gov/disorders/opca/opca.htm |url-status=dead |archive-url=https://web.archive.org/web/20120127104017/http://www.ninds.nih.gov/disorders/opca/opca.htm |archive-date=2012-01-27 }}</ref> OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia (such as the hereditary spinocerebellar ataxia known as [[Machado–Joseph disease]]) and MSA, with which it is primarily associated.<ref name=nidsopca/>

Contrary to most other [[synucleinopathy|synucleinopathies]], which develop α-synuclein inclusions primarily in neuronal cell populations,<ref>{{cite journal | vauthors = Waxman EA, Giasson BI | title = Molecular mechanisms of alpha-synuclein neurodegeneration | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1792 | issue = 7 | pages = 616–624 | date = July 2009 | pmid = 18955133 | pmc = 2756732 | doi = 10.1016/j.bbadis.2008.09.013 }}</ref> MSA presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons.<ref>{{cite journal | vauthors = Burn DJ, Jaros E | title = Multiple system atrophy: cellular and molecular pathology | journal = Molecular Pathology | volume = 54 | issue = 6 | pages = 419–426 | date = December 2001 | pmid = 11724918 | pmc = 1187133 }}</ref> MSA also differs from other synucleinopathies in its regional pathological presentation, with α-synuclein positive inclusions detected predominantly in the striatum, midbrain, pons, medulla and cerebellum,<ref>{{cite journal | vauthors = Ozawa T, Paviour D, Quinn NP, Josephs KA, Sangha H, Kilford L, Healy DG, Wood NW, Lees AJ, Holton JL, Revesz T | display-authors = 6 | title = The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations | journal = Brain | volume = 127 | issue = Pt 12 | pages = 2657–2671 | date = December 2004 | pmid = 15509623 | doi = 10.1093/brain/awh303 | doi-access = free }}</ref><ref name="Converging Patterns of α-Synuclein">{{cite journal | vauthors = Brettschneider J, Suh E, Robinson JL, Fang L, Lee EB, Irwin DJ, Grossman M, Van Deerlin VM, Lee VM, Trojanowski JQ | display-authors = 6 | title = Converging Patterns of α-Synuclein Pathology in Multiple System Atrophy | journal = Journal of Neuropathology and Experimental Neurology | volume = 77 | issue = 11 | pages = 1005–1016 | date = November 2018 | pmid = 30203094 | pmc = 6181179 | doi = 10.1093/jnen/nly080 | doi-access = free }}</ref> rather than the brainstem, limbic and cortical regions typically effected in Lewy inclusion diseases.<ref name="Converging Patterns of α-Synuclein"/> However, recent studies using novel, monoclonal antibodies specific for C-terminally truncated α-synuclein (αSynΔC) have now shown that neuronal α-synuclein pathology is more abundant than previously thought.<ref name="Robust α-synuclein pathology in sel">{{cite journal | vauthors = Hass EW, Sorrentino ZA, Lloyd GM, McFarland NR, Prokop S, Giasson BI | title = Robust α-synuclein pathology in select brainstem neuronal populations is a potential instigator of multiple system atrophy | journal = Acta Neuropathologica Communications | volume = 9 | issue = 1 | pages = 80 | date = May 2021 | pmid = 33941284 | pmc = 8091528 | doi = 10.1186/s40478-021-01173-y | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hass EW, Sorrentino ZA, Xia Y, Lloyd GM, Trojanowski JQ, Prokop S, Giasson BI | title = Disease-, region- and cell type specific diversity of α-synuclein carboxy terminal truncations in synucleinopathies | journal = Acta Neuropathologica Communications | volume = 9 | issue = 1 | pages = 146 | date = August 2021 | pmid = 34454615 | pmc = 8403399 | doi = 10.1186/s40478-021-01242-2 | doi-access = free }}</ref> One group revealed robust α-synuclein pathology in the pontine nuclei and medullary inferior olivary nucleus upon histological analysis of neurological tissue from MSA patients.<ref name="Robust α-synuclein pathology in sel"/>
Histopathological investigation on six cases of pathologically confirmed MSA, using antibodies directed at a variety of α-synuclein epitopes, revealed substantial variation in α-synuclein protein deposition across both cases and brain regions within cases, providing evidence for 'strains' of aggregated conformers that may differentially promote pathological prion-like spread.<ref>{{cite journal | vauthors = Dhillon JS, Trejo-Lopez JA, Riffe C, McFarland NR, Hiser WM, Giasson BI, Yachnis AT | title = Dissecting α-synuclein inclusion pathology diversity in multiple system atrophy: implications for the prion-like transmission hypothesis | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 99 | issue = 7 | pages = 982–992 | date = July 2019 | pmid = 30737468 | pmc = 7209695 | doi = 10.1038/s41374-019-0198-9 | doi-access = free }}</ref>

In 2020, researchers at [[The University of Texas Health Science Center at Houston]] concluded that [[protein misfolding cyclic amplification]] could be used to distinguish between two progressive neurodegenerative diseases, [[Parkinson's disease]] and multiple system atrophy, being the first process to give an objective diagnosis of Multiple System Atrophy instead of just a differential diagnosis.<ref>{{cite news |title=Method Can Distinguish Parkinson's Disease From multiple system atrophy |url=https://www.technologynetworks.com/diagnostics/news/method-can-distinguish-parkinsons-disease-from-multiple-system-atrophy-330385 |access-date=23 February 2020 |work=Diagnostics from Technology Networks |language=en}}</ref><ref name="pmca">{{cite journal | vauthors = Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, Hu B, Schmeichel A, Singer W, Wu G, Tsai AL, Shirani H, Nilsson KP, Low PA, Soto C | display-authors = 6 | title = Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy | journal = Nature | volume = 578 | issue = 7794 | pages = 273–277 | date = February 2020 | pmid = 32025029 | pmc = 7066875 | doi = 10.1038/s41586-020-1984-7 | bibcode = 2020Natur.578..273S }}</ref>