{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:09:16Z","timestamp":1790788156923,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>\n              Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). b-vitamin supplementation with folate and vitamins b\n              <jats:sub>12<\/jats:sub>\n              and b\n              <jats:sub>6<\/jats:sub>\n              reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of b vitamins would reduce the progression of CSVD-related brain lesions.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of b-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of b-vitamin supplementation on the incidence of other ischemic abnormalities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13cm\n              <jats:sup>3<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.419) and incidence of lacunes (8.0% vs 5.9%,\n              <jats:italic>P<\/jats:italic>\n              =0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7cm\n              <jats:sup>3<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.039).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Daily b-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/vitatops.highway1.com.au\/\">http:\/\/vitatops.highway1.com.au\/<\/jats:ext-link>\n              . Unique identifier: NCT00097669 and ISRCTN74743444.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.112.665703","type":"journal-article","created":{"date-parts":[[2012,10,24]],"date-time":"2012-10-24T04:27:57Z","timestamp":1351052877000},"page":"3266-3270","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":78,"title":["B Vitamins and Magnetic Resonance Imaging\u2013Detected Ischemic Brain Lesions in Patients With Recent Transient Ischemic Attack or Stroke"],"prefix":"10.1161","volume":"43","author":[{"given":"Margherita","family":"Cavalieri","sequence":"first","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold","family":"Schmidt","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Mok","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel R.","family":"de Freitas","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swithin","family":"Song","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Yi","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ropele","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Grazer","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Homayoon","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Loh","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Sing Lawrence","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Xiong","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Meng","family":"Chang","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng Cheong","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Fazekas","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme J.","family":"Hankey","sequence":"additional","affiliation":[{"name":"From the Department of Neurology, Medical University of Graz, Austria (M.C., R.S., S.R., A.G., N.H., C.E., F.F.); the Department of Pharmacology, National University of Singapore, Singapore (C.C., M.C.W.); the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (V.M., K.S.L.W., A.W., Y.X.); Universidade Federal do Rio de Janeiro\/ D\u2019Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)00309-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.5.1069"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh023"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00258-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/82.4.806"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000047761"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2007.00111.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.10.1285"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000049766.26453.e9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13616-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/197140099200500413"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10111"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10440"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70187-3"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.5.787"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1258\/0007142991902547"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5923"},{"key":"e_1_3_3_19_2","first-page":"1709","article-title":"The N-methyl-D-aspartate antagonist CNS 1102 protects cerebral gray and white matter from ischemic injury following temporary focal ischemia in rats","volume":"31","author":"Wolf R","year":"2003","unstructured":"Wolf R, Schabitz FL, Fisher M, Pak HC. 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