Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

OBJECTIVE: In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. METHODS: Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. RESULTS: In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. CONCLUSIONS: Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

AIM: To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. MATERIAL AND METHODS: This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. RESULTS: In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. CONCLUSION: The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.