{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:45:31Z","timestamp":1774673131076,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The \u201chot cross bun sign\u201d (HCBs) on magnetic resonance imaging (MRI) has been initially considered specific for multiple system atrophy with cerebellar features. However, a number of other conditions have since been described, which may be associated with this imaging sign. We herein describe a patient with anti-Ri and paraneoplastic cerebellar ataxia, and review the association of the HCBs on imaging with various neurological autoimmune conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a 40-year-old woman with anti-Ri-associated paraneoplastic neurological syndrome and breast carcinoma, in whom brain MRI revealed the HCBs late in the disease course. We also reviewed similar cases reported in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with cerebellar ataxia, polyneuropathy, and pyramidal signs. Although brain MRI was initially unremarkable, the HCBs and T2-weighted hyperintensity of the bilateral middle cerebellar peduncles were observed at later follow-up. Anti-Ri was detected in the serum and cerebrospinal fluid. Breast adenocarcinoma was confirmed <jats:italic>via<\/jats:italic> an axillary lymph node biopsy. Her symptoms partially resolved after the first corticosteroid pulse. However, subsequent immunotherapy and tumor treatments were ineffective. Four autoimmune cerebellar ataxia cases with the HCBs (two paraneoplastic and two non-paraneoplastic) were identified in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The HCBs can be associated with paraneoplastic and non-paraneoplastic cerebellar ataxia, which may reflect neurodegeneration secondary to autoimmune injury. Thus, the HCBs should not be considered a contraindication for autoimmune cerebellar syndrome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.979203","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T07:06:05Z","timestamp":1660892765000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The \u201chot cross bun sign\u201d in patients with autoimmune cerebellar ataxia: A case report and literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Mange","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"592212","DOI":"10.3389\/fnagi.2020.592212","article-title":"Various Diseases and Clinical Heterogeneity Are Associated With \u201cHot Cross Bun\u201d","volume":"12","author":"Zhu","year":"2020","journal-title":"Front Aging Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s00415-020-09702-w","article-title":"Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria","volume":"267","author":"Carr\u00e9","year":"2020","journal-title":"J Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/ana.10518","article-title":"Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments","volume":"53","author":"Pittock","year":"2003","journal-title":"Ann Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.clineuro.2008.06.016","article-title":"Anti-Ri-associated paraneoplastic cerebellar degeneration and breast cancer: an autopsy case study","volume":"110","author":"Brieva-Ru\u00edz","year":"2008","journal-title":"Clin Neurol Neurosurg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3988\/jcn.2009.5.3.151","article-title":"Anti-ri-antibody-associated paraneoplastic syndrome in a man with breast cancer showing a reversible pontine lesion on MRI","volume":"5","author":"Kim","year":"2009","journal-title":"J Clin Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"577345","DOI":"10.1016\/j.jneuroim.2020.577345","article-title":"Anti- RI antibody associated progressive supranuclear palsy like presentation in a patient with breast carcinoma","volume":"347","author":"Takkar","year":"2020","journal-title":"J Neuroimmunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e699","DOI":"10.1212\/NXI.0000000000000699","article-title":"Clinical spectrum and diagnostic pitfalls of neurologic syndromes with Ri antibodies","volume":"7","author":"Simard","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B8","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s12311-015-0728-y","article-title":"The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type","volume":"15","author":"Lin","year":"2016","journal-title":"Cerebellum."},{"key":"B9","doi-asserted-by":"publisher","first-page":"E37","DOI":"10.3174\/ajnr.A1335","article-title":"\u201cHot cross bun\u201d sign in variant Creutzfeldt-Jakob disease","volume":"30","author":"Soares-Fernandes","year":"2009","journal-title":"AJNR Am J Neuroradiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"672","DOI":"10.4103\/0972-2327.120479","article-title":"Hot cross bun sign in HIV-related progressive multifocal leukoencephalopathy","volume":"16","author":"Padmanabhan","year":"2013","journal-title":"Ann Indian Acad Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4103\/0028-3886.137032","article-title":"'Hot-cross bun' and 'inverse trident sign' in progressive multifocal leukoencephalopathy with HIV seropositivity","volume":"62","author":"Jain","year":"2014","journal-title":"Neurol India."},{"key":"B12","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s10072-020-04569-1","article-title":"Hot cross bun sign and prominent cerebellar peduncle involvement in a patient with oculodentodigital dysplasia","volume":"42","author":"Constantinides","year":"2021","journal-title":"Neurol Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"bcr2012006641","DOI":"10.1136\/bcr-2012-006641","article-title":"'Hot cross bun' sign in a case of cerebrotendinous xanthomatosis: a rare neuroimaging observation","volume":"2013","author":"Jain","year":"2013","journal-title":"BMJ Case Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1590\/0004-282X20130132","article-title":"\u201cHot cross bun\u201d sign resembling multiple system atrophy in a patient with Machado-Joseph disease","volume":"71","author":"Pedroso","year":"2013","journal-title":"Arq Neuropsiquiatr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1007\/s10072-016-2635-5","article-title":"Hot cross bun sign in a late-onset SCA1 patient","volume":"37","author":"Wang","year":"2016","journal-title":"Neurol Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1093\/brain\/awh535","article-title":"The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group","volume":"128","author":"Kamm","year":"2005","journal-title":"Brain: J Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/jnnp.71.4.565","article-title":"\u201cHot cross bun\u201d sign in a patient with parkinsonism secondary to presumed vasculitis","volume":"71","author":"Muqit","year":"2001","journal-title":"J Neurol Neurosurg Psychiatr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"37","DOI":"10.14802\/jmd.13009","article-title":"Hot cross bun sign following bilateral pontine infarction: a case report","volume":"6","author":"Roh","year":"2013","journal-title":"J Mov Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12957-015-0483-z","article-title":"'Hot cross bun' sign with leptomeningeal metastases of breast cancer: a case report and review of the literature","volume":"13","author":"Pan","year":"2015","journal-title":"World J Surg Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1017\/S0317167100014736","article-title":"The \u201chot cross bun\u201d sign in leptomeningeal carcinomatosis","volume":"40","author":"Zhang","year":"2013","journal-title":"Canad J Neurol Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1007\/s00415-019-09439-1","article-title":"Hot cross bun sign","volume":"266","author":"Portet","year":"2019","journal-title":"J Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1136\/jnnp.65.1.65","article-title":"Clinical usefulness of magnetic resonance imaging in multiple system atrophy","volume":"65","author":"Schrag","year":"1998","journal-title":"J Neurol Neurosurg Psychiatr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.2169\/internalmedicine.46.0514","article-title":"'Hot-cross Bun Sign' of Multiple System Atrophy","volume":"46","author":"Takao","year":"2007","journal-title":"Intern Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1077","DOI":"10.1212\/NXI.0000000000001077","article-title":"Neurological autoimmunity associated with homer-3 antibody: a case series from China","volume":"8","author":"Liu","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4261","DOI":"10.1111\/ene.15120","article-title":"Long-term MRI changes in a patient with Kelch-like protein 11-associated paraneoplastic neurological syndrome","volume":"28","author":"Ishikawa","year":"2021","journal-title":"Eur J Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jocn.2020.04.052","article-title":"Multiple system atrophy mimicry in MRI: Watch out for paraneoplastic rhombencephalitis","volume":"76","author":"Schlapakow","year":"2020","journal-title":"J Clin Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/ane.12469","article-title":"Paraneoplastic neurological syndrome due to burned-out testicular tumor showing hot cross-bun sign","volume":"133","author":"Ishikawa","year":"2016","journal-title":"Acta Neurol Scand."},{"key":"B28","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1002\/mdc3.13404","article-title":"Homer-3 antibody disease: a potentially treatable MSA-C mimic","volume":"9","author":"Mulroy","year":"2022","journal-title":"Mov Disord Clin Pract."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.979203\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T07:06:07Z","timestamp":1660892767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.979203\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,19]]},"references-count":28,"alternative-id":["10.3389\/fneur.2022.979203"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.979203","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,19]]},"article-number":"979203"}}