{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:29:54Z","timestamp":1787243394943,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug\u2010resistant epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter, double\u2010blind, placebo\u2010controlled, randomized clinical trial, including patients aged \u226515\u2009years with drug\u2010resistant focal or generalized epilepsy. Patients with 25\u2010hydroxyvitamin D (25[OH]D)\u2009&lt;\u200930\u2009ng\/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100\u2009000\u2009IU, five doses in 3\u2009months) or a control group (CG) receiving matched placebo. During the open\u2010label study, EG patients received 100\u2009000\u2009IU\/month for 6\u2009months, whereas CG patients received five doses in 3\u2009months then 1\/month for 3\u2009months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety\u2013depression, and quality of life (Modified Fatigue Impact Scale [M\u2010FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE\u201031]) at 3, 6, and 12\u2009months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3\u2009months. Secondary outcomes were SF and bilateral tonic\u2013clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty\u2010eight patients were enrolled in the study (56 females, aged 17\u201374\u2009years), with median baseline SF per 3 months\u2009=\u200916.5 and \u22652 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was &lt;30\u2009ng\/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3\u2010month blinded period, SF reduction did not significantly differ between groups. However, during the open\u2010label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12\u2009months). BTCSs were reduced by 52%. M\u2010FIS and QOLIE\u201031 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D\u2009&gt;\u200930\u2009ng\/mL for &gt;6\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Despite no proven effect after the 3\u2010month blinded period, the open\u2010label study suggests that long\u2010term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long\u2010term studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT03475225 (03\u201022\u20102018).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18050","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T14:30:07Z","timestamp":1720535407000},"page":"2612-2625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug\u2010resistant epilepsy: A randomized clinical trial"],"prefix":"10.1111","volume":"65","author":[{"given":"Francine","family":"Chassoux","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-8114","authenticated-orcid":false,"given":"Vincent","family":"Navarro","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital and Paris Brain Institute Assistance Publique Hopitaux de Paris, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Quirins","sequence":"additional","affiliation":[{"name":"Department of Neurology Bic\u00eatre Hospital  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Laurent","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Gavaret","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"},{"name":"Institute of Psychiatry and Neuroscience of Paris Universit\u00e9 Paris Cit\u00e9, INSERM UMR 1266  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-5575","authenticated-orcid":false,"given":"Louis","family":"Cousyn","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital and Paris Brain Institute Assistance Publique Hopitaux de Paris, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Cr\u00e9pon","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Landr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Marchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Soufflet","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology Groupe Hospitalier 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