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For longitudinal analysis, we included individuals who had a second <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> with minimum interval of 18 months: 21 patients (10 <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>, 11 <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NL<\/jats:styled-content>) and 11 controls. Three\u2010dimensional (3D) T<jats:sub>1<\/jats:sub>\u2010weighted images acquired in 3 Tesla <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> were analyzed with voxel\u2010based morphometry (<jats:styled-content style=\"fixed-case\">VBM<\/jats:styled-content>). The images of patients with right\u2010sided interictal epileptogenic zone (<jats:styled-content style=\"fixed-case\">EZ<\/jats:styled-content>) were right\u2013left flipped, as well as a comparable proportion of controls. <jats:italic>Cross\u2010sectional analysis<\/jats:italic>: The patients' images from each group were compared to controls to investigate differences in <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> volumes. <jats:italic>Longitudinal analysis<\/jats:italic>: The first and second images were compared in each group to look for decreased <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Cross\u2010sectional analysis<\/jats:italic>: Patients with <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> had diffuse <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> atrophy, including hippocampus and parahippocampal gyrus, insula, frontal, and occipital lobes ipsilateral to <jats:styled-content style=\"fixed-case\">EZ<\/jats:styled-content>, bilateral thalamus and contralateral orbitofrontal gyrus, and caudate. In contrast, <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NL<\/jats:styled-content> group did not present significant differences compared to controls. <jats:italic>Longitudinal analysis<\/jats:italic>:<jats:styled-content style=\"fixed-case\"> TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> presented progressive <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> reduction in ipsilateral insula and occipital lobe, contralateral motor area, and bilateral temporal and frontal lobes. <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NL<\/jats:styled-content> had <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> progression in ipsilateral hypothalamus and parietal lobe, contralateral cerebellum, and bilateral temporal lobe. Controls did not show changes in <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> volume between <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Diffuse extrahippocampal <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> atrophy is present in seizure\u2010free patients with <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>. In addition, there is progressive <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> atrophy in patients with and without <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>. These results demonstrate that not only ongoing seizures are involved in the progression of <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> atrophy. An underlying pathologic mechanism could be responsible for progressive brain volume loss in <jats:styled-content style=\"fixed-case\">TLE<\/jats:styled-content> patients even in seizure\u2010free periods.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13334","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T23:53:28Z","timestamp":1455234808000},"page":"621-629","source":"Crossref","is-referenced-by-count":91,"title":["Progression of gray matter atrophy in seizure\u2010free patients with temporal lobe epilepsy"],"prefix":"10.1111","volume":"57","author":[{"given":"Marina K. 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