title: The relationship between the localization of the generalized spike and wave discharge generators and the response to valproate.
abstract: OBJECTIVE
  Up to 30% of patients with idiopathic generalized epilepsy (IGE) have seizures that are refractory to medication despite appropriate therapy that commonly includes valproate (VPA). The aim of this study was to compare patients with VPA-refractory and VPA-responsive IGE in order to determine whether there are group differences in generalized spike and wave discharge (GSWD) generators that may be associated with VPA resistance.
  
  
  METHODS
  Of 89 IGE patients who underwent electroencephalography (EEG) combined with functional magnetic resonance imaging (fMRI; EEG/fMRI), 25 with GSWDs identified in EEG/fMRI data were included. Simultaneous acquisition of 64 channels of EEG data at 10 kHz was performed using an MRI-compatible EEG cap and amplifier at 4T. VPA resistance was defined as lack of seizure control despite therapeutic dose of VPA.
  
  
  RESULTS
  The fMRI blood oxygen-level dependent (BOLD) correlates of GSWD in the entire group involved midline thalamus, frontal regions comprising Brodmann areas 6, 24, and 32, and temporal lobes diffusely. When VPA-responsive and VPA-resistant patients were compared, BOLD signal increases were noted in the VPA-resistant patients in medial frontal cortex, along the paracingulate gyrus (Montreal Neurological Institute; MNI x = 2, y = 13.6, z = 45.9), and anterior insula bilaterally (right MNI x = 37.6, y = 7.8, z = 0.6, left MNI x = -35.3, y = 13.6, z = -5.3).
  
  
  CONCLUSIONS
  Our findings support the hypothesis that VPA-resistant and VPA-responsive patients may have different GSWD generators. Furthermore, we hypothesize that these differences in GSWD generators may be the reason for different responses to VPA.
authors.affiliation: Department of Neurology and Cincinnati Epilepsy Center, University of Cincinnati, Cincinnati, Ohio, USA. szaflaj@uab.edu
authors.forename: Jerzy P
authors.initials: JP
authors.lastname: Szaflarski
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kay
authors.forename: Jean
authors.initials: J
authors.lastname: Gotman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Privitera
authors.forename: Scott K
authors.initials: SK
authors.lastname: Holland
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D004569:Electroencephalography / Q000379:methods; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D014635:Valproic Acid; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid