{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:53:16Z","timestamp":1770353596150,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1040","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes is a progressive, multisystem mitochondrial disease affecting children and young adults. Patients acquire disability through stroke-like episodes and have an increased mortality. Eighty per cent of cases have the mitochondrial mutation m.3243A&amp;gt;G which is linked to respiratory transport chain dysfunction and oxidative stress in energy demanding organs, particularly muscle and brain. It typically presents with seizures, headaches and acute neurological deficits mimicking stroke. It is an important differential in patients presenting with stroke, seizures, or suspected central nervous system infection or vasculitis. Investigations should exclude other aetiologies and include neuroimaging and cerebrospinal fluid analysis. Mutation analysis can be performed on urine samples. There is no high quality evidence to support the use of any of the agents reported in small studies. This article summarises the core clinical, biochemical, radiological and genetic features and discusses the evidence for a number of potential therapies.<\/jats:p>","DOI":"10.1136\/postgradmedj-2011-130326","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T03:43:37Z","timestamp":1328931817000},"page":"326-334","source":"Crossref","is-referenced-by-count":49,"title":["Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people"],"prefix":"10.1093","volume":"88","author":[{"given":"John Aaron","family":"Goodfellow","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Dani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willie","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celestine","family":"Santosh","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Clinical Physics and Biotechnology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Mulhern","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology, Ayrshire Central Hospital , Irvine, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif","family":"Razvi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neurological Sciences, Southern General Hospital , Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,2,10]]},"reference":[{"key":"2023041906571075700_bib1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/ana.410160409","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes: a distinctive clinical syndrome","volume":"16","author":"Pavlakis","year":"1984","journal-title":"Ann Neurol"},{"key":"2023041906571075700_bib2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/088307389400900102","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS): current concepts","volume":"9","author":"Hirano","year":"1994","journal-title":"J Child Neurol"},{"key":"2023041906571075700_bib3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1212\/WNL.42.3.545","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation","volume":"42","author":"Goto","year":"1992","journal-title":"Neurology"},{"key":"2023041906571075700_bib4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/ana.410310408","article-title":"MELAS: clinical features, biochemistry, and molecular genetics","volume":"31","author":"Ciafaloni","year":"1992","journal-title":"Ann Neurol"},{"key":"2023041906571075700_bib5","article-title":"MELAS: a nationwide prospective cohort study of 96 patients in Japan","author":"Yatsuga","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2023041906571075700_bib6","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1212\/WNL.0b013e31823a0c7f","article-title":"Natural history of MELAS associated with mitochondrial DNA m.3243A&gt;G genotype","volume":"77","author":"Kaufmann","year":"2011","journal-title":"Neurology"},{"key":"2023041906571075700_bib7","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2214\/ajr.166.3.8623642","article-title":"Mitochondrial myopathy-encephalopathy-lactic acidosis- and strokelike episodes (MELAS) syndrome: CT and MR findings in seven children","volume":"166","author":"Kim","year":"1996","journal-title":"AJR Am J Roentgenol"},{"key":"2023041906571075700_bib8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1136\/jnnp.65.2.233","article-title":"Neuroradiological features of six kindreds with MELAS tRNA(Leu) A2342G point mutation: implications for pathogenesis","volume":"65","author":"Sue","year":"1998","journal-title":"J Neurol Neurosurg Psych"},{"key":"2023041906571075700_bib9","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.crad.2007.12.018","article-title":"Differential diagnosis of restricted diffusion confined to the cerebral cortex","volume":"63","author":"Sheerin","year":"2008","journal-title":"Clin Radiol"},{"key":"2023041906571075700_bib10","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1212\/WNL.53.9.2182","article-title":"Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging","volume":"53","author":"Yoneda","year":"1999","journal-title":"Neurology"},{"key":"2023041906571075700_bib11","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s00234-003-1029-6","article-title":"Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema","volume":"45","author":"Wang","year":"2003","journal-title":"Neuroradiology"},{"key":"2023041906571075700_bib12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00593950","article-title":"Fluctuating MR images with mitochondrial encephalopathy, lactic acidosis, stroke-like syndrome (MELAS)","volume":"32","author":"Abe","year":"1990","journal-title":"Neuroradiology"},{"key":"2023041906571075700_bib13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3348\/kjr.2011.12.1.15","article-title":"Diffusion and perfusion characteristics of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode) in thirteen patients","volume":"12","author":"Kim","year":"2011","journal-title":"Korean J Radiol"},{"issue":"2","key":"2023041906571075700_bib14","first-page":"233","article-title":"MELAS syndrome: imaging and proton MR spectroscopic findings","volume":"16","author":"Castillo","year":"1995","journal-title":"AJNR Am J Neuroradiol"},{"key":"2023041906571075700_bib15","first-page":"1958","article-title":"Proton MR spectroscopy of mitochondrial diseases: analysis of brain metabolic abnormalities and their possible diagnostic significance","author":"Bianchi","year":"2003","journal-title":"Am J Neuroradiol"},{"issue":"5\u20136","key":"2023041906571075700_bib16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.mito.2008.05.003","article-title":"Neuroimaging of mitochondrial disease","volume":"8","author":"Saneto","year":"2008","journal-title":"Mitochondrion"},{"key":"2023041906571075700_bib17","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.mito.2009.01.011","article-title":"PET imaging of redox and energy states in stroke-like episodes of MELAS","volume":"9","author":"Ikawa","year":"2009","journal-title":"Mitochondrion"},{"key":"2023041906571075700_bib18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1017\/S0317167100003929","article-title":"Pathology of mitochondrial encephalomyopathies","volume":"32","author":"Sarnat","year":"2005","journal-title":"Can J Neurol Sci"},{"key":"2023041906571075700_bib19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.mito.2009.01.004","article-title":"The study of mitochondrial A3243G mutation in different samples","volume":"9","author":"Ma","year":"2009","journal-title":"mitochondrion"},{"key":"2023041906571075700_bib20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ymgme.2010.02.024","article-title":"Current molecular diagnostic algorithm for mitochondrial disorders","volume":"100","author":"Wong","year":"2010","journal-title":"Mol Genet Metab"},{"key":"2023041906571075700_bib21","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/348651a0","article-title":"A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encenphalomyopathies","volume":"348","author":"Goto","year":"1990","journal-title":"Nature"},{"key":"2023041906571075700_bib22","first-page":"655","article-title":"Genetic analysis of three pedigrees of mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS)","volume":"50","author":"Sato","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2023041906571075700_bib23","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1086\/301959","article-title":"Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population","volume":"63","author":"Majamaa","year":"1998","journal-title":"Am J Hum Genet"},{"key":"2023041906571075700_bib24","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ajhg.2008.07.004","article-title":"Pathogenic mitochondrial DNA mutations are common in the general population","volume":"83","author":"Elliott","year":"2008","journal-title":"Am J Hum Genet"},{"key":"2023041906571075700_bib25","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1086\/316930","article-title":"Decrease of 3243 A\u2014&gt;G mtDNA mutation from blood in MELAS syndrome: a longitudinal study","volume":"68","author":"Rahman","year":"2001","journal-title":"Am J Hum Genet"},{"key":"2023041906571075700_bib26","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1006\/bbrc.1994.2119","article-title":"A new point mutation at nucleotide pair 3291 of the mitochondrial tRNA (Leu(UUR)) gene in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)","volume":"202","author":"Goto","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"2023041906571075700_bib27","first-page":"1055","article-title":"A mitochondrial tRNA(leu)(UUR) mutation at 3256 associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)","volume":"33","author":"Sato","year":"1994","journal-title":"Biochem Mol Biol Int"},{"key":"2023041906571075700_bib28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1212\/WNL.56.3.405","article-title":"Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation","volume":"56","author":"Bataillard","year":"2001","journal-title":"Neurology"},{"key":"2023041906571075700_bib29","first-page":"480","article-title":"Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes","volume":"12","author":"King","year":"1992","journal-title":"Mol Cell Biol"},{"key":"2023041906571075700_bib30","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1136\/jnnp.50.11.1475","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes with recurrent abdominal symptoms and coenzyme Q10 administration","volume":"50","author":"Yamamoto","year":"1987","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2023041906571075700_bib31","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1212\/WNL.42.11.2147","article-title":"MELAS syndrome with mitochondrial tRNALeu (UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin","volume":"42","author":"Penn","year":"1992","journal-title":"Neurology"},{"key":"2023041906571075700_bib32","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1212\/01.WNL.0000151976.60624.01","article-title":"L-Arginine improves the symptoms of strokelike episodes in MELAS","volume":"64","author":"Koga","year":"2005","journal-title":"Neurology"},{"issue":"1","key":"2023041906571075700_bib33","first-page":"CD004426","article-title":"Treatment for mitochondrial disorders","author":"Chinnery","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"key":"2023041906571075700_bib34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0022-510X(90)90015-F","article-title":"Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial","volume":"100","author":"Bresolin","year":"1990","journal-title":"J Neurol Sci"},{"key":"2023041906571075700_bib35","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1212\/WNL.47.2.583","article-title":"Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS","volume":"47","author":"Ikejiri","year":"1996","journal-title":"Neurology"},{"key":"2023041906571075700_bib36","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.mito.2006.11.006","article-title":"MELAS and L-arginine therapy","volume":"7","author":"Koga","year":"2007","journal-title":"Mitochondrion"},{"key":"2023041906571075700_bib37","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1212\/WNL.58.5.827","article-title":"Effects of L-arginine on the acute phase of strokes in three patients with MELAS","volume":"58","author":"Koga","year":"2002","journal-title":"Neurology"},{"key":"2023041906571075700_bib38","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1212\/WNL.42.11.2147","article-title":"MELAS syndrome with mitochondrial tRNALeu (UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin","volume":"42","author":"Penn","year":"1992","journal-title":"Neurology"},{"key":"2023041906571075700_bib39","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1212\/01.wnl.0000196641.05913.27","article-title":"Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial","volume":"66","author":"Kaufmann","year":"2006","journal-title":"Neurology"},{"key":"2023041906571075700_bib40","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1093\/hmg\/8.6.1047","article-title":"Gene shifting: a novel therapy for mitochondrial myopathy","volume":"8","author":"Taivassalo","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2023041906571075700_bib41","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/ana.20240","article-title":"Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells","volume":"56","author":"Santra","year":"2004","journal-title":"Ann Neurol"},{"key":"2023041906571075700_bib42","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/hmg\/ddq076","article-title":"Ketogenic diet slows down mitochondrial myopathy progression in mice","volume":"19","author":"Ahola-Erkkila","year":"2010","journal-title":"Hum Mol Genet"},{"key":"2023041906571075700_bib43","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/ng.258","article-title":"The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes","volume":"40","author":"Wai","year":"2008","journal-title":"Nat Genet"},{"key":"2023041906571075700_bib44","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/nature08958","article-title":"Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease","volume":"465","author":"Craven","year":"2010","journal-title":"Nature"}],"container-title":["Postgraduate Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/88\/1040\/326\/50018386\/postgradmedj-88-326.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/88\/1040\/326\/50018386\/postgradmedj-88-326.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T07:00:46Z","timestamp":1681887646000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pmj\/article\/88\/1040\/326\/6986753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,10]]},"references-count":44,"journal-issue":{"issue":"1040","published-online":{"date-parts":[[2012,2,10]]},"published-print":{"date-parts":[[2012,6,1]]}},"URL":"https:\/\/doi.org\/10.1136\/postgradmedj-2011-130326","relation":{},"ISSN":["0032-5473","1469-0756"],"issn-type":[{"value":"0032-5473","type":"print"},{"value":"1469-0756","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,6]]},"published":{"date-parts":[[2012,2,10]]}}}