{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:59:54Z","timestamp":1792166394539,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Purpose<\/jats:title>\n Mitochondrial Encephalomyopathy, Lactic acidosis and Stroke\u2010like episodes (MELAS) is a rare multisystem mitochondrial disorder with clinical heterogeneity. Diagnostic criteria and management strategies for MELAS and mitochondrial stroke\u2010like episodes (SLE) remain inconsistent. This work provides international consensus recommendations on the definition, diagnosis, and management of MELAS and SLE in pediatric and adult populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n An international Delphi consensus process was conducted within the European Reference Network for Neuromuscular Diseases (ERN EURO\u2010NMD), in collaboration with the US Mitochondrial Medicine Society, the ERN for Hereditary Metabolic Disorders (MetabERN), and patient representatives. Following a systematic literature review, 54 statements addressing diagnostic definitions and management of MELAS were evaluated. Statements not reaching consensus were revised and re\u2010evaluated during a face\u2010to\u2010face meeting.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Consensus supported defining MELAS as a clinical syndrome characterized by one or more SLE in the context of mitochondrial dysfunction caused by a pathogenic mitochondrial DNA variant, particularly m.3243A>G in\n MT\u2010TL1<\/jats:italic>\n . The use of terms such as \u201cMELAS\u2010like\u201d or \u201cMELAS spectrum\u201d was discouraged. The panel agreed that the efficacy of L\u2010arginine, L\u2010taurine, L\u2010citrulline, coenzyme Q\n 10<\/jats:sub>\n , vitamins, and other supplements remains unproven and requires validation in clinical trials. Antiseizure medications should be initiated promptly when seizures are suspected during SLE, and intravenous corticosteroids may be beneficial acutely. Multidisciplinary management of neurological, neuropsychiatric, and systemic complications was endorsed.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This international consensus provides updated definitions and practical guidance for the diagnosis and management of MELAS and SLE, aiming to harmonize clinical practice and inform future evidence\u2010based research.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ene.70588","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T08:11:16Z","timestamp":1776499876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Diagnostic Criteria and Management of\n MELAS<\/scp>\n and Stroke\u2010Like Episodes: Consensus\u2010Based Statements"],"prefix":"10.1111","volume":"33","author":[{"given":"Michelangelo","family":"Mancuso","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute University of Pisa Pisa Italy"},{"name":"CTMM \u2013 Interdepartmental Research Centre for Translational Medicine in Neuromuscular and Mitochondrial Diseases University of Pisa Pisa Italy"},{"name":"Azienda Ospedaliero Universitaria Pisana Neurological Clinic Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Bellusci","sequence":"additional","affiliation":[{"name":"Reference Center for Inherited Metabolic Disorders MetabERN, Mitochondrial Disorders Research Group (imas12) '12 de Octubre' University Hospital Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Carelli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna Programma di Neurogenetica Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irenaeus","family":"de Coo","sequence":"additional","affiliation":[{"name":"Mental Health and Neuroscience Research Institute, Graduate School MHeNS, Department Translational Genomics Maastricht University Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Diodato","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Diseases Children Hospital Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-7848","authenticated-orcid":false,"given":"Felix","family":"Distelmaier","sequence":"additional","affiliation":[{"name":"University Children's Hospital D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Hikmat","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Haukeland University Hospital Bergen Norway"},{"name":"Department of Clinical Science (K2) University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Hirano","sequence":"additional","affiliation":[{"name":"H. Houston Merritt Neuromuscular Research Center, Department of Neurology Columbia University Irving Medical Center New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-170X","authenticated-orcid":false,"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Karaa","sequence":"additional","affiliation":[{"name":"Division of Genetics Massachusetts General Hospital\/Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klopstock","sequence":"additional","affiliation":[{"name":"Department of Neurology, Friedrich\u2010Baur\u2010Institute LMU University Hospital, Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kay","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Child & Adolescent Neurology University of Texas McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Kornblum","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Center for Neurology University Hospital Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"La Morgia","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"},{"name":"IRCCS Istituto Delle Scienze Neurologiche di Bologna,UOC Clinica Neurologica Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piervito","family":"Lopriore","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Neurological Institute University of Pisa Pisa Italy"},{"name":"Scuola Superiore Sant'anna, Ph.D School in Translational Medicine Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika Henrik","family":"Martikainen","sequence":"additional","affiliation":[{"name":"Research Unit of Clinical Medicine University of Oulu Oulu Finland"},{"name":"Neurocenter Oulu University Hospital Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McFarland","sequence":"additional","affiliation":[{"name":"Mitochondrial Research Group Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK"},{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olimpia","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Neurology and Neuromuscular Disorders University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D. S.","family":"Pitceathly","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases University College London Queen Square Institute of Neurology London UK"},{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders, the National Hospital for Neurology and Neurosurgery London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-7008","authenticated-orcid":false,"given":"Guido","family":"Primiano","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Organi di Senso e Torace Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy"},{"name":"Dipartimento Di Neuroscienze Universit\u00e0 Cattolica del Sacro Cuore Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-730X","authenticated-orcid":false,"given":"Shamima","family":"Rahman","sequence":"additional","affiliation":[{"name":"Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-8460","authenticated-orcid":false,"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine\/Texas Children's Hospital Houston Texas USA"},{"name":"Baylor Genetics Houston Texas USA"},{"name":"Joint BCM\u2010CUHK Center of Medical Genetics Prince of Wales Hospital Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Schaefer","sequence":"additional","affiliation":[{"name":"NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-232X","authenticated-orcid":false,"given":"Manuel","family":"Schiff","sequence":"additional","affiliation":[{"name":"Reference Center for Mitochondrial Disorders (CARAMMEL) and Reference Center for Inborn Errors of Metabolism, Department of Pediatrics, Necker\u2010Enfants\u2010Malades Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris University of Paris\u2010Cit\u00e9 Paris France"},{"name":"INSERM UMRS_1163 Imagine Institute Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Semmler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum Rechts der Isar Technical University Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Lamperti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico C. 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