title: Progression of gray matter atrophy in seizure-free patients with temporal lobe epilepsy.
abstract: OBJECTIVE
  To investigate the presence and progression of gray matter (GM) reduction in seizure-free patients with temporal lobe epilepsy (TLE).
  
  
  METHODS
  We enrolled 39 consecutive TLE patients, seizure-free for at least 2 years--20 with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 19 with normal MRI (TLE-NL), and 74 healthy controls. For longitudinal analysis, we included individuals who had a second MRI with minimum interval of 18 months: 21 patients (10 TLE-HS, 11 TLE-NL) and 11 controls. Three-dimensional (3D) T1 -weighted images acquired in 3 Tesla MRI were analyzed with voxel-based morphometry (VBM). The images of patients with right-sided interictal epileptogenic zone (EZ) were right-left flipped, as well as a comparable proportion of controls. Cross-sectional analysis: The patients' images from each group were compared to controls to investigate differences in GM volumes. Longitudinal analysis: The first and second images were compared in each group to look for decreased GM volume.
  
  
  RESULTS
  Cross-sectional analysis: Patients with TLE-HS had diffuse GM atrophy, including hippocampus and parahippocampal gyrus, insula, frontal, and occipital lobes ipsilateral to EZ, bilateral thalamus and contralateral orbitofrontal gyrus, and caudate. In contrast, TLE-NL group did not present significant differences compared to controls. Longitudinal analysis: TLE-HS presented progressive GM reduction in ipsilateral insula and occipital lobe, contralateral motor area, and bilateral temporal and frontal lobes. TLE-NL had GM progression in ipsilateral hypothalamus and parietal lobe, contralateral cerebellum, and bilateral temporal lobe. Controls did not show changes in GM volume between MRIs.
  
  
  CONCLUSIONS
  Diffuse extrahippocampal GM atrophy is present in seizure-free patients with TLE-HS. In addition, there is progressive GM atrophy in patients with and without HS. These results demonstrate that not only ongoing seizures are involved in the progression of GM atrophy. An underlying pathologic mechanism could be responsible for progressive brain volume loss in TLE patients even in seizure-free periods.
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Marina K M
authors: MK
authors: Alvim
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Ana C
authors: AC
authors: Coan
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Brunno M
authors: http://orcid.org/0000-0003-1261-8257
authors: BM
authors: Campos
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Clarissa L
authors: CL
authors: Yasuda
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Mariana C
authors: MC
authors: Oliveira
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Marcia E
authors: ME
authors: Morita
authors: Department of Neurology, Neuroimaging Laboratory, State University of Campinas, Campinas, São Paulo, Brazil.
authors: Fernando
authors: F
authors: Cendes
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000175:diagnosis / Q000503:physiopathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D066128:Gray Matter / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures
keywords: Gray matter atrophy; Magnetic resonance imaging; Voxel-based morphometry