Abstracts

Rationale: Focal cortical dysplasia (FCD) is associated with refractory epilepsy in children. Widely accepted classification of FCD separates Type I from II based on the presence of cortical dyslamination and dysmorphic/cytomegalic neurons. Recently, several studies reported overexpression of mammalian target of rapamycin (mTOR) observed predominantly in pathologic specimen with Type II FCD despite the absence of difference in seizure severity and epilepsy duration between the two FCD Types. To understand the role of mTOR activation, we studied the presence of mTOR immunohistochemistry in relation with FCD Types, severity of gliosis, and surgical outcome. Methods: We identified 36 patients who had the pathologically confirmed diagnosis of FCD between Jan 2007 and Nov 2010 from the epilepsy surgery database. All 36 patients underwent surgical resection for refractory focal epilepsy following comprehensive clinical and imaging evaluation including scalp V-EEG, FDG-PET, MRI, SISCOM and intracranial EEG. In addition to standard H&E stain, glial fibrilary acidic protein (GFAP) and mTOR immunohistochemistry (IHC) was performed. GFAP IHC was classified as either superficial (sGFAP: subpial and lst layer of cortex) or diffuse (dGFAP: all 6 layers) based on the extent of involvement. mTOR IHC was considered positive if the specimen showed more than 2 dysmorphic neurons showing positive cytoplasmic staining. This study was approved by the IRB at CCHMC.Results: Total of 36 patients were included (ages 1-20; 19 females). Overall, 17 patient became seizure-free at the last f/u (mean f/u duration 17 mo: 6-53 mo). There were 56 resection specimens due to multi-lobar surgeries or repeat surgeries in the same patients. Resection locations were frontal (33), temporal (16), parietal (6) and occipital (1). Twenty-seven patients showed only 1 FCD type: IA 2, IB 13, IIA 11, and IIB 2. Nine patients had combination of FCD types. Overall FCD classification by highest FCD Type was IA (6), IB (23), IIA (24), and IIB (3). mTOR IHC was positive in 24% (7/29) of Type I and 74% (20/27) of Type II FCD. dGFAP was noted in 17% (5/29) of Type I and 89% (24/27) of Type II. All brain specimens classified as Type IA FCD showed sGFAP and negative mTOR IHC. In contrast, 100% of specimens classified as Type IIB showed dGFAP and positive mTOR IHC. There was no difference in surgical outcome based on FCD types, presence of mTOR IHC, or GFAP IHC. Conclusions: Our study showed that mTOR activation and diffuse cortical gliosis are present in FCD Type IB and Type II, but not in FCD Type 1A. The lack of correlation between the mTOR IHC and surgical outcome suggests that mTOR activation is not necessarily related to epileptogenesis, but rather to abnormal neuronal growth. Further prospective studies of mTOR activation in other epileptic brain specimens may provide better understanding of epileptogenesis in developing brain.