{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:51:12Z","timestamp":1767703872880,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited genetic mitochondrial disease with a typical onset in the first two decades of life and a major involvement of central nervous system (CNS). We present the case of a man affected with an oligosymptomatic, genetically determined MELAS syndrome, whose clinical picture dramatically and irreversibly worsened following a mild head injury. We hypothesize that the CNS metabolic stress induced by the brain injury activated an irreversible cascade of events leading to progressive neurodegeneration because damaged mitochondria were unable to restore the balance between energy requirements and availability.<\/jats:p>","DOI":"10.3390\/metabo13010046","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:42:48Z","timestamp":1672206168000},"page":"46","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Traumatic Brain Injury Triggers Neurodegeneration in a Mildly Symptomatic MELAS Patient: Implications on the Detrimental Role of Damaged Mitochondria in Determining Head Trauma Sequalae in the General Population"],"prefix":"10.3390","volume":"13","author":[{"given":"Simona","family":"Zanotti","sequence":"first","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1837-2788","authenticated-orcid":false,"given":"Daniele","family":"Velardo","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Sciacco","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41439-018-0026-6","article-title":"Mitochondrial DNA 3243A>T mutation in a patient with MELAS syndrome","volume":"5","author":"Ikeda","year":"2018","journal-title":"Hum. Genome Var."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/chd.12634","article-title":"Mitochondrial DNA mutation \u201cm.3243A>G\u201d-Heterogeneous clinical picture for cardiologists (\u201cm.3243A>G\u201d: A phenotypic chameleon)","volume":"13","author":"Niedermayr","year":"2018","journal-title":"Congenit. Heart Dis."},{"key":"ref_3","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":"ref_4","unstructured":"Adam, M.P., Everman, D.B., Mirzaa, G.M., Pagon, R.A., and Wallace, S.E. (2001). MELAS. GeneReviews\u00ae, University of Washington."},{"key":"ref_5","first-page":"234","article-title":"CT and MR of MELAS syndrome","volume":"9","author":"Ailard","year":"1988","journal-title":"Am. J. Neuroradiol."},{"key":"ref_6","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":"ref_7","doi-asserted-by":"crossref","first-page":"132931","DOI":"10.1016\/j.neulet.2017.06.050","article-title":"Inflammation and mitochondrial dysfunction: A vicious circle in neurodegenerative disorders?","volume":"710","author":"Witte","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134347","DOI":"10.1016\/j.neulet.2019.134347","article-title":"Mitochondrial dysfunctioning and neuroinflammation: Recent highlights on the possible mechanisms involved in Traumatic Brain Injury","volume":"710","author":"Kaira","year":"2019","journal-title":"Neurosci. 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Trauma Acute Care Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1002\/jimd.12196","article-title":"Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus","volume":"43","author":"Brown","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/toxsci\/kfy008","article-title":"Mitochondrial Toxicity","volume":"162","author":"Meyer","year":"2018","journal-title":"Toxicol. Sci."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/1\/46\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:53:21Z","timestamp":1760147601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/1\/46"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":16,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["metabo13010046"],"URL":"https:\/\/doi.org\/10.3390\/metabo13010046","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}