title: Quantitative MRI detects abnormalities in relatives of patients with epilepsy and malformations of cortical development.
abstract: Malformations of cortical development (MCD) are a common etiology for epilepsy. Laminar heterotopia, bilateral subependymal heterotopia, and lissencephaly have a genetic basis. No gene mutations have yet been identified in patients with focal cortical dysplasias. The aim of this study was to use quantitative morphometric tools to determine if there were gray matter abnormalities in relatives of patients with MCD. We studied 19 relatives of 13 probands with MCD and 58 healthy controls with high-resolution MRI. The relatives and controls had no neocortical abnormalities on visual inspection. MRI data were analyzed with voxel-based morphometry and autoblock analysis. Voxel-based morphometry showed significant increases of gray matter in 9 of 10 probands, 5 of 19 relatives, and 5 of 58 controls. The autoblock analysis showed significant abnormalities in 7 of 8 probands, 8 of 19 relatives, and 2 of 57 controls. This finding suggests structural abnormality in the brains of a greater number of relatives of MCD patients than would be expected, and in the context, a reasonable inference is that this reflects subtle genetically determined cerebral abnormalities, although acquired pathologies are possible and are not excluded.
authors.affiliation: Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Merschhemke
authors.forename: T N
authors.initials: TN
authors.lastname: Mitchell
authors.forename: S L
authors.initials: SL
authors.lastname: Free
authors.forename: A
authors.initials: A
authors.lastname: Hammers
authors.forename: L
authors.initials: L
authors.lastname: Kinton
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
authors.forename: J
authors.initials: J
authors.lastname: Stevens
authors.forename: B
authors.initials: B
authors.lastname: Kendall
authors.forename: H J
authors.initials: HJ
authors.lastname: Meencke
authors.forename: J S
authors.initials: JS
authors.lastname: Duncan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology; D004292:Dominance, Cerebral / Q000502:physiology; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008432:Mathematical Computing; D008875:Middle Aged; D009421:Nervous System Malformations / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity