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A comprehensive review of the literature helped to circumstantiate our findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our research in the FPDB identified six patients who, within 3\u00a0days from their first cycle of 5\u2010FU or capecitabine, developed acute neurological symptoms, including gait ataxia (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), dysarthria (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), dysmetria (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), headache (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), and confusion (<jats:italic>n<\/jats:italic>\u00a0=\u00a02). Brain magnetic resonance imaging (MRI) showed T2\/FLAIR (fluid\u2010attenuated inversion recovery) hyperintensities in the corpus callosum, with diffusion restriction and no contrast enhancement, generally accompanied by additional alterations in the bilateral supratentorial white matter (<jats:italic>n<\/jats:italic>\u00a0=\u00a05). All patients discontinued the agent supposedly responsible for the toxicity and experienced full recovery after a median of 8.5\u00a0days from symptom onset. Control MRI showed a progressive normalization of acute MRI abnormalities. Literature review identified 26 cases with similar clinical and paraclinical characteristics. A single patient from the literature resumed 5\u2010FU at a lower dose, with no recurrent toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>5\u2010FU and capecitabine might be responsible for acute leukoencephalopathies with transient splenial lesions that are generally reversible upon drug discontinuation. Resuming the agent responsible for toxicity might be feasible in selected cases, after having excluded dihydropyrimidine dehydrogenase deficiency, if expected benefits outweigh the risks.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14857","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T07:51:31Z","timestamp":1617609091000},"page":"2396-2402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Leukoencephalopathy with transient splenial lesions related to 5\u2010fluorouracil or capecitabine"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-375X","authenticated-orcid":false,"given":"Valentine","family":"Perrain","sequence":"first","affiliation":[{"name":"AP\u2010HP H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re \u2010 Charles Foix Service de Neurologie 2\u2010Mazarin Sorbonne Universit\u00e9 Inserm CNRS UMR S 1127 Institut du 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