{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:43:17Z","timestamp":1790430197488,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T00:00:00Z","timestamp":1617580800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["18H02533"],"award-info":[{"award-number":["18H02533"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Karin & Sten Mortstedt CBS Solutions. Queen Square Brain Bank for Neurological Disorders"},{"name":"Reta Lila Weston Institute of Neurological Studies"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014667","name":"British Neuropathological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014667","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Research UK Research Fellowship"},{"name":"Department of Health\u2019s NIHR Biomedical Research Centre"},{"DOI":"10.13039\/501100008721","name":"UCLH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008721","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Reta Lila Weston Trust"},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["N013255\/1"],"award-info":[{"award-number":["N013255\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Multiple System Atrophy Coalition"},{"DOI":"10.13039\/501100006282","name":"King Baudouin Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006282","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Karin & Sten Morstedt CBD Solutions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We studied a subset of patients with autopsy-confirmed multiple system atrophy who presented a clinical picture that closely resembled either Parkinson\u2019s disease or progressive supranuclear palsy. These mimics are not captured by the current diagnostic criteria for multiple system atrophy. Among 218 autopsy-proven multiple system atrophy cases reviewed, 177 (81.2%) were clinically diagnosed and pathologically confirmed as multiple system atrophy (i.e. typical cases), while the remaining 41 (18.8%) had received an alternative clinical diagnosis, including Parkinson\u2019s disease (i.e. Parkinson\u2019s disease mimics; n\u2009=\u200916) and progressive supranuclear palsy (i.e. progressive supranuclear palsy mimics; n\u2009=\u200917). We also reviewed the clinical records of another 105 patients with pathologically confirmed Parkinson\u2019s disease or progressive supranuclear palsy, who had received a correct final clinical diagnosis (i.e. Parkinson\u2019s disease, n\u2009=\u200935; progressive supranuclear palsy-Richardson syndrome, n\u2009=\u200935; and progressive supranuclear palsy-parkinsonism, n\u2009=\u200935). We investigated 12 red flag features that would support a diagnosis of multiple system atrophy according to the current diagnostic criteria. Compared with typical multiple system atrophy, Parkinson\u2019s disease mimics more frequently had a good levodopa response and visual hallucinations. Vertical gaze palsy and apraxia of eyelid opening were more commonly observed in progressive supranuclear palsy mimics. Multiple logistic regression analysis revealed an increased likelihood of having multiple system atrophy [Parkinson\u2019s disease mimic versus typical Parkinson\u2019s disease, odds ratio (OR): 8.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.3] if a patient developed any one of seven selected red flag features in the first 10 years of disease. Severe autonomic dysfunction (orthostatic hypotension and\/or urinary incontinence with the need for a urinary catheter) was more frequent in clinically atypical multiple system atrophy than other parkinsonian disorders (Parkinson\u2019s disease mimic versus typical Parkinson\u2019s disease, OR: 4.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 8.8). The atypical multiple system atrophy cases more frequently had autonomic dysfunction within 3 years of symptom onset than the pathologically confirmed patients with Parkinson\u2019s disease or progressive supranuclear palsy (Parkinson\u2019s disease mimic versus typical Parkinson\u2019s disease, OR: 4.7; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.7). Using all included clinical features and 21 early clinical features within 3 years of symptom onset, we developed decision tree algorithms with combinations of clinical pointers to differentiate clinically atypical cases of multiple system atrophy from Parkinson\u2019s disease or progressive supranuclear palsy.<\/jats:p>","DOI":"10.1093\/brain\/awab017","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T07:43:01Z","timestamp":1611733381000},"page":"1138-1151","source":"Crossref","is-referenced-by-count":56,"title":["Identification of multiple system atrophy mimicking Parkinson\u2019s disease or progressive supranuclear palsy"],"prefix":"10.1093","volume":"144","author":[{"given":"Yasuo","family":"Miki","sequence":"first","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Tsushima","sequence":"additional","affiliation":[{"name":"Department of Comprehensive Rehabilitation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine C","family":"Foti","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M","family":"Strand","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine T","family":"Asi","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam Kenji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK"},{"name":"Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concei\u00e7\u00e3o","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos C B","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), S\u00e3o Paulo, Brazil"},{"name":"Neurology Unit, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP), Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-2515","authenticated-orcid":false,"given":"Eduardo","family":"De Pablo-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-4385","authenticated-orcid":false,"given":"Andrew J","family":"Lees","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas T","family":"Warner","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niall","family":"Quinn","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice L","family":"Holton","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Ling","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"},{"name":"Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"key":"2021072420413922000_awab017-B1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000131165","article-title":"D\u00e9g\u00e9n\u00e9rescences nigro-stri\u00e9es et c\u00e9r\u00e9bello-nigro-stri\u00e9es. (Unicit\u00e9 clinique et variabilit\u00e9 pathologique des d\u00e9g\u00e9n\u00e9rescences pr\u00e9s\u00e9nile \u00e0 forme de rigidit\u00e9 extrapyramidale)","volume":"142","author":"Adams","year":"1961","journal-title":"Eur Neurol"},{"key":"2021072420413922000_awab017-B2","first-page":"330","article-title":"L\u2019atrophie olivo-ponto-c\u00e9r\u00e9belleuse","volume":"13","author":"D\u00e9jerine","year":"1900","journal-title":"Nouv Iconogr Salp\u00eatr."},{"key":"2021072420413922000_awab017-B3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/jnnp.32.1.28","article-title":"Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy","volume":"32","author":"Graham","year":"1969","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"2021072420413922000_awab017-B4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/archneur.1960.03840110025004","article-title":"A neurological syndrome associated with orthostatic hypotension: A clinical-pathological study","volume":"2","author":"Shy","year":"1960","journal-title":"Ama Arch Neurol."},{"key":"2021072420413922000_awab017-B5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0022-510X(89)90219-0","article-title":"Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome)","volume":"94","author":"Papp","year":"1989","journal-title":"J Neurol Sci."},{"key":"2021072420413922000_awab017-B6","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0022-510X(92)90286-T","article-title":"Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy","volume":"107","author":"Papp","year":"1992","journal-title":"J Neurol Sci."},{"key":"2021072420413922000_awab017-B7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0304-3940(98)00407-8","article-title":"\u03b1-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy","volume":"249","author":"Wakabayashi","year":"1998","journal-title":"Neurosci Lett."},{"key":"2021072420413922000_awab017-B8","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","article-title":"Second consensus statement on the diagnosis of multiple system atrophy","volume":"71","author":"Gilman","year":"2008","journal-title":"Neurology."},{"key":"2021072420413922000_awab017-B9","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S1474-4422(15)00058-7","article-title":"Natural history of multiple system atrophy in the USA: A prospective cohort study","volume":"14","author":"Low","year":"2015","journal-title":"Lancet Neurol."},{"key":"2021072420413922000_awab017-B10","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S1474-4422(12)70327-7","article-title":"The natural history of multiple system atrophy: A prospective European cohort 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