title: Focal decreases of cortical GABAA receptor binding remote from the primary seizure focus: what do they indicate?
abstract: OBJECTIVE
  To determine the electroclinical significance and histopathological correlates of cortical gamma-aminobutyric acid(A)(GABA(A)) receptor abnormalities detected in and remote from human neocortical epileptic foci.
  
  
  METHODS
  Cortical areas with decreased(11)C-flumazenil (FMZ) binding were objectively identified on positron emission tomography (PET) images and correlated to intracranial electroencephalography (EEG) findings, clinical seizure variables, histology findings, and surgical outcome in 20 patients (mean age, 9.9 years) with intractable partial epilepsy of neocortical origin and nonlocalizing magnetic resonance imaging (MRI).
  
  
  RESULTS
  Focal decrease of cortical FMZ binding was detected in the lobe of seizure onset in 17 (85%) patients. Eleven patients (55%) had 17 remote cortical areas with decreased FMZ binding outside the lobe of seizure onset. Thirteen of those 16 (81%) of the 17 remote cortical regions that were covered by subdural EEG were around cortex showing rapid seizure spread on intracranial EEG. Remote FMZ PET abnormalities were associated with high seizure frequency and, when resected, showed gliosis in all six cases where material was available. Higher number of unresected cortical regions with decreased FMZ binding was associated with poorer surgical outcome.
  
  
  CONCLUSIONS
  Focal decreases of cortical GABA(A) receptor binding on PET may include cortical regions remote from the primary focus, particularly in patients with high seizure frequency, and these regions are commonly involved in rapid seizure propagation. Although these regions may not always need to be resected to achieve seizure freedom, a careful evaluation of cortex with decreased GABA(A) receptor binding prior to resection using intracranial EEG may facilitate optimal surgical outcome in patients with intractable neocortical epilepsy.
authors.affiliation: Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan and Harper University Hospital, Detroit Medical Center, Wayne State University School of Medcine, Detroit, Michigan, USA. juhasz@pet.wayne.edu
authors.forename: Csaba
authors.initials: C
authors.lastname: Juhász
authors.forename: Eishi
authors.initials: E
authors.lastname: Asano
authors.forename: Aashit
authors.initials: A
authors.lastname: Shah
authors.forename: Diane C
authors.initials: DC
authors.lastname: Chugani
authors.forename: Carlos E A
authors.initials: CE
authors.lastname: Batista
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sood
authors.forename: Harry T
authors.initials: HT
authors.lastname: Chugani
mesh_terms: D000293:Adolescent; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D004292:Dominance, Cerebral / Q000502:physiology; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D017034:Epilepsy, Frontal Lobe / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics; D005911:Gliosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D019579:Neocortex / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000378:metabolism*; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil