title: Callosal alterations in pyridoxine-dependent epilepsy.
abstract: OBJECTIVE
  While there have been isolated reports of callosal morphology differences in pyridoxine-dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1 gene mutations, no study has systematically evaluated callosal features in a large sample of patients. This study sought to overcome this knowledge gap.
  
  
  METHODS
  Spanning a wide age range from birth to 48 years, corpus callosum morphology and cross-sectional cerebral area were measured in 30 individuals with PDE (12 males, 18 females, median age 3.92y; 25th centile 0.27, 75th centile 15.25) compared to 30 age-matched comparison individuals (11 males, 19 females, median age 3.85y; 25th centile 0.26, 75th centile 16.00). Individuals with PDE were also divided into age groups to evaluate findings across development. As delay to treatment may modulate clinical severity, groups were stratified by treatment delay (less than or greater than 2wks from birth).
  
  
  RESULTS
  Markedly reduced callosal area expressed as a ratio of mid-sagittal cerebral area was observed for the entire group with PDE (p<0.001). Stratifying by age (<1y, 1-10y, >10y) demonstrated posterior abnormalities to be a consistent feature, with anterior regions increasingly involved across the developmental trajectory. Splitting the PDE group by treatment lag did not reveal overall or sub-region callosal differences.
  
  
  CONCLUSIONS
  Callosal abnormalities are a common feature of PDE not explained by treatment lag. Future work utilizing tract-based approaches to understand inter- and intra-hemispheric connectivity patterns will help in the better understanding the structural aspects of this disease.
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Friedman
authors.forename: Gisele E
authors.initials: GE
authors.lastname: Ishak
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Poliachik
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Poliakov
authors.forename: Randolph K
authors.initials: RK
authors.lastname: Otto
authors.forename: Dennis W W
authors.initials: DW
authors.lastname: Shaw
authors.forename: Michèl A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Bok
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Gospe
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics; D016022:Case-Control Studies; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology*; D004827:Epilepsy / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation
chemical_list: C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase