{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:54:17Z","timestamp":1778712857347,"version":"3.51.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Stroke-like episodes (SLEs) in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with m.3243A\u2009&gt;\u2009G mutation usually develop in the cerebral cortex. Few reports have documented SLEs in the cerebellum. The clinical neuroimaging features of cerebellar SLEs have not been fully investigated. We report distinctive features of cerebellar stroke-like lesions (SLLs) in a case of MELAS with m.3243A\u2009&gt;\u2009G mutation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>A 47-year-old Japanese man with type-2 diabetes presented to our hospital with acute onset of aphasia. A brain MRI obtained on admission (day 1) showed increased diffusion-weighted imaging (DWI)\/fluid-attenuated inversion recovery (FLAIR) signal in the left anterolateral temporal lobe, which subsequently spread along the cortex posteriorly accompanied by a new lesion in the right anterior temporal lobe. The patient was initially treated with acyclovir and subsequently with immunotherapy. However, on day 45, cerebellar ataxia developed. The brain MRI showed extensive increased DWI\/FLAIR signals in the cerebellum along the folia without involvement of deep cerebellar nucleus or cerebellar peduncle; SLLs were incongruent with a vascular territory, similarly to classic cerebral SLLs. Apparent diffusion coefficient (ADC) map did not show reduction in ADC values in the affected folia. Genomic analysis revealed m.3243A\u2009&gt;\u2009G mutation (heteroplasmy in leukocytes, 17%), confirming the diagnosis of MELAS. After the treatment with taurine (12,000\u2009mg\/day), L-arginine (12,000\u2009mg\/day), vitamin B1 (100\u2009mg\/day), and carnitine (3000\u2009mg\/day), the patient became able to follow simple commands, and he was transferred to a rehabilitation center on day 146. The follow-up MRI showed diffuse brain atrophy, including the cerebellum.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>SLLs develop in the cerebellum in MELAS with m.3243A\u2009&gt;\u2009G mutation. The neuroimaging similarities to cerebral SLLs suggest the presence of the common pathophysiological mechanisms underlying both SLEs, which include microangiopathy and increased susceptibility of the cortex to metabolic derangements.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12883-020-01748-7","type":"journal-article","created":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T13:02:36Z","timestamp":1588338156000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neuroimaging pattern and pathophysiology of cerebellar stroke-like lesions in MELAS with m.3243A&gt;G mutation: a case report"],"prefix":"10.1186","volume":"20","author":[{"given":"Munenori","family":"Oyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Iizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Nakahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-4660","authenticated-orcid":false,"given":"Yoshikane","family":"Izawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,1]]},"reference":[{"issue":"4","key":"1748_CR1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/ana.410160409","volume":"16","author":"SG Pavlakis","year":"1984","unstructured":"Pavlakis SG, Phillips PC, Dimauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16(4):481\u20138.","journal-title":"Ann Neurol"},{"key":"1748_CR2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.12688\/wellcomeopenres.15599.1","volume":"4","author":"YS Ng","year":"2019","unstructured":"Ng YS, Bindoff LA, Gorman GS, Horvath R, et al. Consensus-based statements for the management of mitochondrial stroke-like episodes. Wellcome Open Res. 2019;4:201.","journal-title":"Wellcome Open Res"},{"issue":"1","key":"1748_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2174\/1567202052773544","volume":"2","author":"T Iizuka","year":"2005","unstructured":"Iizuka T, Sakai F. Pathogenesis of stroke-like episodes in MELAS: analysis of neurovascular cellular mechanisms. Curr Neurovasc Res. 2005;2(1):29\u201345.","journal-title":"Curr Neurovasc Res"},{"key":"1748_CR4","doi-asserted-by":"publisher","first-page":"116726","DOI":"10.1016\/j.jns.2020.116726","volume":"412","author":"J Finsterer","year":"2020","unstructured":"Finsterer J. Aliyev Rahim. Metabolic stroke or stroke-like lesion: peculiarities of a phenomenon. J Neurol. Science (2020). J Neurol Sci. 2020;412:116726.","journal-title":"J Neurol Sci"},{"issue":"6","key":"1748_CR5","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1212\/WNL.59.6.816","volume":"59","author":"T Iizuka","year":"2002","unstructured":"Iizuka T, Sakai F, Suzuki N, et al. Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome. Neurology. 2002;59(6):816\u201324.","journal-title":"Neurology."},{"issue":"9","key":"1748_CR6","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1212\/01.WNL.0000091888.26232.FE","volume":"61","author":"T Iizuka","year":"2003","unstructured":"Iizuka T, Sakai F, Kan S, Suzuki N. Slowly progressive spread of the stroke-like lesions in MELAS. Neurology. 2003;61(9):1238\u201344.","journal-title":"Neurology."},{"issue":"6","key":"1748_CR7","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/s00415-019-09283-3","volume":"266","author":"Y Hongo","year":"2019","unstructured":"Hongo Y, Kaneko J, Suga H, Ishima D, Kitamura E, Akutsu T, et al. A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features. J Neurol. 2019;266(6):1459\u201372.","journal-title":"J Neurol"},{"issue":"2","key":"1748_CR8","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1097\/NEN.0b013e318244477d","volume":"71","author":"NZ Lax","year":"2012","unstructured":"Lax NZ, Hepplewhite PD, Reeve AK, Nesbitt V, McFarland R, Jaros E, et al. Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study. J Neuropathol Exp Neurol. 2012;71(2):148\u201361.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"Pt 6","key":"1748_CR9","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1093\/brain\/aws110","volume":"135","author":"NZ Lax","year":"2012","unstructured":"Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, et al. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain. 2012;135(Pt 6):1736\u201350.","journal-title":"Brain."},{"issue":"12","key":"1748_CR10","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.2169\/internalmedicine.2190-18","volume":"58","author":"D Muramatsu","year":"2019","unstructured":"Muramatsu D, Yamaguchi H, Iwasa K, Yamada M. Cerebellar hyperintensity lesions on diffusion-weighted MRI in MELAS. Intern Med. 2019;58(12):1797\u20138.","journal-title":"Intern Med"},{"issue":"11","key":"1748_CR11","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1212\/WNL.0000000000003713","volume":"88","author":"M Spatola","year":"2017","unstructured":"Spatola M, Petit-Pedrol M, Simabukuro MM, et al. Investigations in GABAA receptor antibody-associated encephalitis. Neurology. 2017;88(11):1012\u201320.","journal-title":"Neurology."},{"key":"1748_CR12","first-page":"30461","volume":"19","author":"H Ueno","year":"2019","unstructured":"Ueno H, Iizuka T, Tagane Y, et al. Focal hyperperfusion and elevated lactate in the cerebral lesions with anti-GABAaR encephalitis: a serial MRI study. J Neuroradiol. 2019;19:30461\u20134.","journal-title":"J Neuroradiol"},{"issue":"4","key":"1748_CR13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","volume":"15","author":"F Graus","year":"2016","unstructured":"Graus F, Titulaer JM, Balu R, et al. Clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391\u2013404.","journal-title":"Lancet Neurol"},{"issue":"6","key":"1748_CR14","first-page":"615","volume":"40","author":"P Samuel","year":"1962","unstructured":"Samuel P. Hicks, Marie coy Cavanaugh, and Elaine D. O'Brien. Effects of anoxia on the developing cerebral cortex in the rat. Am J Pathol. 1962;40(6):615\u201335.","journal-title":"Am J Pathol"},{"issue":"3","key":"1748_CR15","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1007\/BF00688185","volume":"74","author":"E Ohama","year":"1987","unstructured":"Ohama E, Ohara S, Ikuta F, Tanaka K, Nishizawa M, Miyatake T. Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuropathol. 1987;74(3):226\u201333.","journal-title":"Acta Neuropathol"},{"issue":"3","key":"1748_CR16","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1007\/s00415-013-7225-3","volume":"261","author":"M Mancuso","year":"2014","unstructured":"Mancuso M, Orsucci D, Angelini C, et al. The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender? J Neurol. 2014;261(3):504\u201310.","journal-title":"J Neurol"},{"issue":"3","key":"1748_CR17","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/acn3.532","volume":"5","author":"SJ Pickett","year":"2018","unstructured":"Pickett SJ, Grady JP, Ng YS, et al. Phenotypic heterogeneity in m.3243A>G mitochondrial disease: the role of nuclear factors. Ann Clin Transl Neurol. 2018;5(3):333\u201345.","journal-title":"Ann Clin Transl Neurol"},{"issue":"9","key":"1748_CR18","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1212\/WNL.53.9.2182","volume":"53","author":"M Yoneda","year":"1999","unstructured":"Yoneda M, Maeda M, Kimura H, Fujii A, Katayama K, Kuriyama M. Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology. 1999;53(9):2182\u20134.","journal-title":"Neurology."}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-01748-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-020-01748-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-01748-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T12:24:45Z","timestamp":1620044685000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-020-01748-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1748"],"URL":"https:\/\/doi.org\/10.1186\/s12883-020-01748-7","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,1]]},"assertion":[{"value":"9 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"n\/a.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The written informed consent has been obtained from the patient for publication of this case report and any accompanying images.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JN is an Editorial Board Member of BMC Neurology. MO reports no disclosure. TI receives a grant from The Japan Epilepsy Research Foundation and research support from Astellas Pharma Inc. JN receives research grants from Daiichi-Sankyo, Eisai, B\u00f6ehringer-Ingelheim, and Pfizer. YI receives grants from Keio University Program for the Advancement of Next Generation Research Projects. The authors declare that this case report was not conducted in the commercial or financial relationships that could be constructed as a potential conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"167"}}