{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:09:28Z","timestamp":1774026568736,"version":"3.50.1"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"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>Introduction<\/jats:title><jats:p>Verbal auditory agnosia is rarely caused by mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Lactate acidosis, which is the adverse effect of metformin, has proposed links to mitochondrial dysfunction and may trigger clinical features of mitochondrial diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>A 43-year-old right-handed man presented to our emergency department with acute onset fever and headache accompanied by impaired hearing comprehension. He could communicate well through handwritten notes but could not understand what others were saying. He had been diagnosed as having diabetes mellitus 2 months prior to this event. Vildagliptin 100 mg\/day and metformin 1,700 mg\/day were prescribed for glucose control. Laboratory tests revealed elevated lactate levels in serum and cerebrospinal fluid of the patient. Brain MRI disclosed bilateral temporal lesions. Acute encephalitis with temporal involved was initially diagnosed and acyclovir was given empirically. However, follow-up MRI after acyclovir treatment revealed a progression of prior lesions. Further mitochondrial genome analysis revealed a mitochondrial DNA point mutation at position 3,243 (m.3243A &amp;gt; G) with 25% heteroplasmy, which is compatible with MELAS. His clinical symptoms and serum lactate levels were improved after discontinuing the metformin use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To our knowledge, this is the first report of a patient having late-onset MELAS syndrome that manifested as acute verbal auditory agnosia, which was identified after the patient began using metformin. Metformin is known to inhibit mitochondrial function and could trigger clinical features of MELAS syndrome. We encourage clinicians to maintain a high level of awareness that diabetes mellitus can be caused by mitochondrial disease and to exercise caution in the prescription of metformin.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.863047","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T17:58:19Z","timestamp":1648576699000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Case Report: Late-Onset Mitochondrial Disease Uncovered by Metformin Use in a Patient With Acute Verbal Auditory Agnosia"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei-Hao","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Hsiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-En","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Fen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/NRL.0000000000000229","article-title":"Late-onset mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes presenting with auditory agnosia","volume":"24","author":"Smith","year":"2019","journal-title":"The neurologist."},{"key":"B2","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1124\/mol.63.4.844","article-title":"Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin","volume":"63","author":"Wang","year":"2003","journal-title":"Mol Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/S1474-4422(21)00098-3","article-title":"Mitochondrial disease in adults: recent advances and future promise","volume":"20","author":"Ng","year":"2021","journal-title":"Lancet Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/0960-8966(92)90045-8","article-title":"Melas: an original case and clinical criteria for diagnosis","volume":"2","author":"Hirano","year":"1992","journal-title":"Neuromusc Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s10072-008-1028-9","article-title":"Acute auditory agnosia as the presenting hearing disorder in MELAS","volume":"29","author":"Miceli","year":"2008","journal-title":"Neurol Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/B978-0-444-62630-1.00032-9","article-title":"Auditory agnosia","volume":"129","author":"Slevc","year":"2015","journal-title":"Handbook Clin Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.ymgme.2015.06.004","article-title":"MELAS syndrome: clinical manifestations, pathogenesis, and treatment options","volume":"116","author":"El-Hattab","year":"2015","journal-title":"Mol Genet Metab."},{"key":"B8","doi-asserted-by":"publisher","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":"De Vries","year":"2020","journal-title":"J Inherit Metab Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"124","DOI":"10.7326\/L20-0292","article-title":"MELAS syndrome and MIDD unmasked by metformin use: a case report","volume":"174","author":"Kim","year":"2021","journal-title":"Ann Intern Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e15487","DOI":"10.7759\/cureus.15487","article-title":"Stroke-like lesion in an m","volume":"13","author":"Finsterer","year":"2021","journal-title":"Cureus."},{"key":"B11","first-page":"46","article-title":"Adult onset MELAS syndrome presenting as a mimic of herpes simplex encephalitis","volume":"28","author":"Chen","year":"2019","journal-title":"Acta Neurol Taiwan."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.863047\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T17:58:22Z","timestamp":1648576702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.863047\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":11,"alternative-id":["10.3389\/fneur.2022.863047"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.863047","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,25]]},"article-number":"863047"}}