title: Increased subcortical oligodendroglia-like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones.
abstract: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy.
  
  
  
  We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome.
  
  
  
  Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028).
  
  
  
  Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone.
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakuma
authors.affiliation: Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: William C
authors.initials: WC
authors.lastname: Halliday
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ruka
authors.initials: R
authors.lastname: Nomura
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Shiro
authors.initials: S
authors.lastname: Baba
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okanari
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Midori
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Division of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Elysa
authors.initials: E
authors.lastname: Widjaja
authors.affiliation: Division of Neurology, BC Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Boelman
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ochi
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: O Carter
authors.initials: OC
authors.lastname: Snead
authors.affiliation: Department of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.affiliation: Department of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Drake
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Miller
authors.affiliation: Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otsubo
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D000069279:Drug Resistant Epilepsy / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D004569:Electroencephalography; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009836:Oligodendroglia / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010751:Phosphopyruvate Hydratase
keywords: Epileptic spasm; Gray-white matter junction; Multiple-lobe resection; Pediatric epilepsy surgery; White matter