{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:12:31Z","timestamp":1772169151822,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15758.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>Stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome but occur in other mitochondrial disorders (MIDs) as well. The morphological equivalent of the SLE is the stroke-like lesion (SLL) on magnetic resonance imaging (MRI). The pathophysiology of SLLs is under debate, but several hypotheses have been raised to explain the phenomenon. Of these, the metabolic, epileptogenic, and vascular hypotheses are the most frequently discussed. There are several arguments for and against these hypotheses, but a consensus has not been reached which of them provides the correct explanation. A recent consensus statement generated by a panel of experts applying the Delphi method, favoured the epileptogenic hypothesis and recommended treatment of SLEs with antiepileptic drugs, irrespective if the patient presented with a seizure or epileptiform discharges on electroencephalography (EEG) or not. We disagree with this general procedure and provide the following arguments against the epileptogenic hypothesis: 1. not each SLE is associated with seizures. 2. epileptiform discharges may be absent on EEG during a SLE. 3. SLLs are not restricted to the cortex. 4. antiseizure-drugs (ASDs) may not prevent the progression or recurrence of a SLL. 5. ASDs may terminate seizures but no other phenotypic feature of a SLE. 6. patients already under ASDs are not immune from developing a SLL. 7. SLLs usually last longer than seizures. 8. no animal model supports the epileptogenic hypothesis. The strongest arguments for the metabolic hypothesis are that SLLs are not confined to a vascular territory, that the oxygen-extraction fraction within a SLL is reduced, and that there is hypometabolism within a SLL on FDG-PET. SLLs may respond to antioxidants, NO-precursors, steroids, or the ketogenic diet. ASDs should be applied only if there is clinical or electrophysiological evidence of seizure-activity.<\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15758.2","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T12:10:41Z","timestamp":1593000641000},"page":"51","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2839-7305","authenticated-orcid":false,"given":"Josef","family":"Finsterer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.12688\/wellcomeopenres.15599.1","article-title":"Consensus-based 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17283.r38255, Claude Steriade, Epilepsy Center, New York University Langone Health, New York City, NY, USA, 14 Apr 2020, version 1, 1 approved, 1 not approved","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-51\/v1#referee-response-38255","order":0,"name":"referee-response-38255","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>josef finsterer<\/b>; \n<i>Posted: 18 Apr 2020<\/i>; Thank you for these valuable comments","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-51\/v2#referee-comment-4120","order":1,"name":"referee-comment-4120","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17664.r39228, Mirian C.H. Janssen, Amalia Children\u2019s Hospital, Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, The Netherlands, 29 Jun 2020, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-51\/v2#referee-response-39228","order":2,"name":"referee-response-39228","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The authors declared that no grants were involved in supporting this work.\n\nAs a Correspondence to an article published on Wellcome Open Research, The Wellcome Trust covered the APC for this article; however, the Wellcome Trust was not involved in funding this work.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}