title: Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration.
abstract: OBJECTIVE
  To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure.
  
  
  METHODS
  Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses.
  
  
  RESULTS
  LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy.
  
  
  CONCLUSIONS
  Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.
authors.affiliation: The Magnetic Resonance and Image Analysis Research Centre (MARIARC), Pembroke Place, University of Liverpool, Liverpool, UK. kellers@liv.ac.uk
authors.forename: S S
authors.initials: SS
authors.lastname: Keller
authors.forename: U C
authors.initials: UC
authors.lastname: Wieshmann
authors.forename: C E
authors.initials: CE
authors.lastname: Mackay
authors.forename: C E
authors.initials: CE
authors.lastname: Denby
authors.forename: J
authors.initials: J
authors.lastname: Webb
authors.forename: N
authors.initials: N
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000473:pathology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004292:Dominance, Cerebral / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D003294:Seizures, Febrile / Q000175:diagnosis* / Q000209:etiology; D013702:Temporal Lobe / Q000473:pathology