{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T22:00:13Z","timestamp":1785708013872,"version":"3.56.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,19]]},"DOI":"10.7759\/cureus.32709","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T22:34:51Z","timestamp":1671489291000},"source":"Crossref","is-referenced-by-count":10,"title":["Arginine for the Treatment of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes: A Systematic Review"],"prefix":"10.7759","author":[{"given":"Jennifer M","family":"Argudo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M","family":"Astudillo Moncayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Insuasti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Garofalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex S","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Encalada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Villamarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"O\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriela","family":"Tenemaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Eissa-Garc\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakina","family":"Matcheswalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Fernando","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1444.011","article-title":"Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome","volume":"1142","author":"Sproule DM","year":"2008","unstructured":"Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008, 1142:133-58. 10.1196\/annals.1444.011","journal-title":"Ann N Y Acad Sci"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.09.005","article-title":"Molecular pathology of MELAS and L-arginine effects","volume":"1820","author":"Koga Y","year":"2012","unstructured":"Koga Y, Povalko N, Nishioka J, Katayama K, Yatsuga S, Matsuishi T. Molecular pathology of MELAS and L-arginine effects. Biochim Biophys Acta. 2012, 1820:608-14. 10.1016\/j.bbagen.2011.09.005","journal-title":"Biochim Biophys Acta"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.648740","article-title":"MELAS\/LS overlap syndrome associated with mitochondrial DNA mutations: clinical, genetic, and radiological studies","volume":"12","author":"Wei Y","year":"2021","unstructured":"Wei Y, Huang Y, Yang Y, Qian M. MELAS\/LS overlap syndrome associated with mitochondrial DNA mutations: clinical, genetic, and radiological studies. Front Neurol. 2021, 12:648740. 10.3389\/fneur.2021.648740","journal-title":"Front Neurol"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1253\/circj.cj-10-0044","article-title":"Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion. C-11 acetate kinetics revealed by positron emission tomography","volume":"74","author":"Arakawa K","year":"2010","unstructured":"Arakawa K, Kudo T, Ikawa M, et al.. Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion. C-11 acetate kinetics revealed by positron emission tomography. Circ J. 2010, 74:2702-11. 10.1253\/circj.cj-10-0044","journal-title":"Circ J"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2018.10.051","article-title":"Clinical profile and outcome of cardiac involvement in MELAS syndrome","volume":"276","author":"Brambilla A","year":"2019","unstructured":"Brambilla A, Favilli S, Olivotto I, et al.. Clinical profile and outcome of cardiac involvement in MELAS syndrome. Int J Cardiol. 2019, 276:14-9. 10.1016\/j.ijcard.2018.10.051","journal-title":"Int J Cardiol"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1625","article-title":"Wolff-Parkinson-White syndrome in patients with MELAS","volume":"64","author":"Sproule DM","year":"2007","unstructured":"Sproule DM, Kaufmann P, Engelstad K, Starc TJ, Hordof AJ, De Vivo DC. Wolff-Parkinson-White syndrome in patients with MELAS. Arch Neurol. 2007, 64:1625-7. 10.1001\/archneur.64.11.1625","journal-title":"Arch Neurol"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.4.5.631","article-title":"Diagnosis and management of MELAS","volume":"4","author":"Thambisetty M","year":"2004","unstructured":"Thambisetty M, Newman NJ. Diagnosis and management of MELAS. Expert Rev Mol Diagn. 2004, 4:631-44. 10.1586\/14737159.4.5.631","journal-title":"Expert Rev Mol Diagn"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.03.015","article-title":"MELAS: a nationwide prospective cohort study of 96 patients in Japan","volume":"1820","author":"Yatsuga S","year":"2012","unstructured":"Yatsuga S, Povalko N, Nishioka J, et al.. MELAS: a nationwide prospective cohort study of 96 patients in Japan. Biochim Biophys Acta. 2012, 1820:619-24. 10.1016\/j.bbagen.2011.03.015","journal-title":"Biochim Biophys Acta"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000229921.41817.94","article-title":"Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial","volume":"67","author":"Savolainen H","year":"2006","unstructured":"Savolainen H. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006, 67:184. 10.1212\/01.wnl.0000229921.41817.94","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-317964","article-title":"Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial","volume":"90","author":"Ohsawa Y","year":"2019","unstructured":"Ohsawa Y, Hagiwara H, Nishimatsu SI, et al.. Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial. J Neurol Neurosurg Psychiatry. 2019, 90:529-36. 10.1136\/jnnp-2018-317964","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.675816","article-title":"Epilepsy associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes","volume":"12","author":"Li J","year":"2021","unstructured":"Li J, Zhang W, Cui Z, Li Z, Jiang T, Meng H. Epilepsy associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Front Neurol. 2021, 12:675816. 10.3389\/fneur.2021.675816","journal-title":"Front Neurol"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200620060-00002","article-title":"The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options","volume":"20","author":"Scaglia F","year":"2006","unstructured":"Scaglia F, Northrop JL. The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options. CNS Drugs. 2006, 20:443-64. 10.2165\/00023210-200620060-00002","journal-title":"CNS Drugs"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.644535","article-title":"Mitochondrial toxicity of antiepileptic drugs and their tolerability in mitochondrial disorders","volume":"8","author":"Finsterer J","year":"2012","unstructured":"Finsterer J, Zarrouk Mahjoub S. Mitochondrial toxicity of antiepileptic drugs and their tolerability in mitochondrial disorders. Expert Opin Drug Metab Toxicol. 2012, 8:71-9. 10.1517\/17425255.2012.644535","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher D","year":"2009","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009, 6:e1000097. 10.1371\/journal.pmed.1000097","journal-title":"PLoS Med"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins JP","year":"2011","unstructured":"Higgins JP, Altman DG, G\u00f8tzsche PC, et al.. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011, 343:d5928. 10.1136\/bmj.d5928","journal-title":"BMJ"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-9057-7","article-title":"Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research","volume":"265","author":"Koga Y","year":"2018","unstructured":"Koga Y, Povalko N, Inoue E, et al.. Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research. J Neurol. 2018, 265:2861-74. 10.1007\/s00415-018-9057-7","journal-title":"J Neurol"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000220197.36849.1e","article-title":"Endothelial dysfunction in MELAS improved by l-arginine supplementation","volume":"66","author":"Koga Y","year":"2006","unstructured":"Koga Y, Akita Y, Junko N, et al.. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006, 66:1766-9. 10.1212\/01.wnl.0000220197.36849.1e","journal-title":"Neurology"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000151976.60624.01","article-title":"L-arginine improves the symptoms of strokelike episodes in MELAS","volume":"64","author":"Koga Y","year":"2005","unstructured":"Koga Y, Akita Y, Nishioka J, et al.. L-arginine improves the symptoms of strokelike episodes in MELAS. Neurology. 2005, 64:710-2. 10.1212\/01.WNL.0000151976.60624.01","journal-title":"Neurology"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2004.11.026","article-title":"Hypocitrullinemia in patients with MELAS: an insight into the \"MELAS paradox\"","volume":"229","author":"Naini A","year":"2005","unstructured":"Naini A, Kaufmann P, Shanske S, Engelstad K, De Vivo DC, Schon EA. Hypocitrullinemia in patients with MELAS: an insight into the \"MELAS paradox\". J Neurol Sci. 2005, 229:187-93. 10.1016\/j.jns.2004.11.026","journal-title":"J Neurol Sci"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-020-00384-5","article-title":"Therapeutic potential of citrulline as an arginine supplement: a clinical pharmacology review","volume":"22","author":"Rashid J","year":"2020","unstructured":"Rashid J, Kumar SS, Job KM, Liu X, Fike CD, Sherwin CM. Therapeutic potential of citrulline as an arginine supplement: a clinical pharmacology review. Paediatr Drugs. 2020, 22:279-93. 10.1007\/s40272-020-00384-5","journal-title":"Paediatr Drugs"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00772-x","article-title":"Clinical features, pathogenesis, and management of stroke-like episodes due to MELAS","volume":"36","author":"Tetsuka S","year":"2021","unstructured":"Tetsuka S, Ogawa T, Hashimoto R, Kato H. Clinical features, pathogenesis, and management of stroke-like episodes due to MELAS. Metab Brain Dis. 2021, 36:2181-93. 10.1007\/s11011-021-00772-x","journal-title":"Metab Brain Dis"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1177\/2326409817697399","article-title":"Arginine and citrulline for the treatment of MELAS syndrome","volume":"5","author":"El-Hattab AW","year":"2017","unstructured":"El-Hattab AW, Almannai M, Scaglia F. Arginine and citrulline for the treatment of MELAS syndrome. J Inborn Errors Metab Screen. 2017, 5:10.1177\/2326409817697399","journal-title":"J Inborn Errors Metab Screen"},{"key":"ref23","unstructured":"L-arginine therapy on endothelium-dependent vasodilation &amp; mitochondrial metabolism in MELAS syndrome. (2013). Accessed. June 11, 2022: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT01603446."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200489","article-title":"Progesterone-associated arginine decline at luteal phase of menstrual cycle and associations with related amino acids and nuclear factor kB activation","volume":"13","author":"Faustmann G","year":"2018","unstructured":"Faustmann G, Meinitzer A, Magnes C, et al.. Progesterone-associated arginine decline at luteal phase of menstrual cycle and associations with related amino acids and nuclear factor kB activation. PLoS One. 2018, 13:e0200489. 10.1371\/journal.pone.0200489","journal-title":"PLoS One"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238224","article-title":"L-arginine effects on cerebrovascular reactivity, perfusion and neurovascular coupling in MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome","volume":"15","author":"Rodan LH","year":"2020","unstructured":"Rodan LH, Poublanc J, Fisher JA, Sobczyk O, Mikulis DJ, Tein I. L-arginine effects on cerebrovascular reactivity, perfusion and neurovascular coupling in MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome. PLoS One. 2020, 15:e0238224. 10.1371\/journal.pone.0238224","journal-title":"PLoS One"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/119154-arginine-for-the-treatment-of-mitochondrial-encephalopathy-lactic-acidosis-and-stroke-like-episodes-a-systematic-review","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T19:46:20Z","timestamp":1707507980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/119154-arginine-for-the-treatment-of-mitochondrial-encephalopathy-lactic-acidosis-and-stroke-like-episodes-a-systematic-review"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,19]]},"references-count":25,"URL":"https:\/\/doi.org\/10.7759\/cureus.32709","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12,19]]}}}