Increased subcortical oligodendroglia-like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). SIGNIFICANCE: 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.

Increased population of oligodendroglia-like cells in pediatric intractable epilepsy.

Pediatric focal epilepsies often involve more extratemporal regions than adult epilepsies. This study aims to investigate the population of oligodendroglia-like cells (OLCs) in the pediatric focal epilepsy patients requiring surgery. We hypothesize that OLCs are one of the factors that extend the pediatric epileptic network in intractable epilepsy. Thirty (18 female) patients (1.8-16.9 years old with a mean of 9.7 years), who underwent resective surgery for the intractable epilepsy from 2010 to 2012 were retrospectively studied. Seizure types consisted of epileptic spasms in nine patients, partial seizures in 17 patients and partial seizure with secondary generalization in four patients. Eight autopsy cases without neurological disease served as controls. The neuropathology examination utilized the H&E/LFB stain and immunohistochemical staining for NeuN, GFAP and Olig2 as a marker of OLCs. OLCs were counted in three sites: (a) gray matter, (b) junction of gray/white matter, and (c) white matter. We also examined the correlation between the density of OLC among the three sites and the clinical features. Fifteen (50%) patients underwent multiple lobe resections, consisting of both temporal and extratemporal lobe resections in 12 patients and extratemporal lobe resections in 3 patients. The other 15 (50%) patients underwent single lobe resection including 3 (10%) patients with temporal lobectomy sparing hippocampus. Pathological diagnosis of epilepsy patients was as follows: 14 (47%) patients=focal cortical dysplasia (type I, 4; II, 9; III, 1); 6 (20%)=oligodendrogliosis; 6 (20%)=astrocytic gliosis; 2 (7%)=hyaline protoplasmic astrocytopathy and 2 (7%)=tuberous sclerosis complex. The numbers of OLCs at all three sites in epilepsy group were significantly higher than those of control group (p<0.001). In the epilepsy group, there was a significant difference among the number of OLCs at gray matter, junction of gray and white matter, and white matter (p<0.001). The number of OLCs significantly increased from gray matter and junction of gray/white matter to white matter. In the control group, there was no difference among the number of OLCs at three sites. There was no significant difference in the numbers of OLCs between focal cortical dysplasia types I and II. The significantly increased OLCs, especially in the white matter may contribute to the extensive epileptic network in children with intractable focal epilepsy.