Abstracts

Rationale: Focal Cortical Dysplasias (FCDs) are frequent cause of intractable epilepsy. Despite increasing numbers of AEDs available, large proportions of patients with FCDs continue to have seizures. It is now recognized that epileptogenicity in FCDs is a more complex network extending beyond FCD lesion, and epilepsy due to FCDs is not a static but a progressive disease. Little is known about epileptogenic substrate in epileptogenic networks. We investigated growth associated protein 43 (GAP-43), a marker for growth cones associated with axonal growth and regeneration and synaptic plasticity, as the potential substrate for progressive epileptogenesis in FCDs. Methods: Neocortical specimens resected during epilepsy surgery were used for GAP-43 immunohitochemistry (IHC). Specimens with diagnosis of type III FCDs were excluded. FCDs were diagnosed by Palmini 2004 classification. Non-temporal lobe specimens with FCD were included: 12 with FCD II (II A or II B), 9 with IA were available for analysis. 20 temporal lobe specimens with hippocampal sclerosis but free of any other pathology were used as control specimen. A semi-quantitative analysis of GAP43 IHC was performed. Two outcome categories were used: seizure free vs not seizure free. Fisher s exact test was used to compare GAP-43 scores with outcome and Logistic Fit was used to measure the relationship between GAP43 scores and epilepsy duration. Results: GAP43 IHC did not show neuronal cytosolic staining. Cell surface (rim) staining and tubular punctuate (punctuate) staining are the elements to be graded. Rim staining: 4 = >50% of neurons in the section have GAP-43 stained RIM pattern; 3= ~ 40% neurons in the section have GAP-43 stained RIM pattern; 2= ~ 5%-10% neurons in the section have GAP-43 stained RIM pattern; 1= few neuron in the section have GAP-43 stained RIM pattern. Intensity of Tubular punctuate: 4= dark; 3= moderately dark; 2= some staining; 1= no staining. The final grade was obtained by adding scores for Rim and Tubular staining. GAP-43 and Epilepsy duration: Only in FCD IIA/B group, higher GAP-43 protein scores significantly correlated with longer duration of epilepsy ( <0.0001). The patients in FCD IA group had shorter epilepsy duration: within that duration span, GAP-43 did not correlate with epilepsy duration. In MTS group, epilepsy duration span was similar to that of FCD IIA/B group; however GAP-43 did not correlate with epilepsy duration. GAP-43 and outcomes: In FCD IA group, outcomes were variable despite overall low GAP-43 scores. In FCD IIA/B group, lower GAP43 score associated better chances of seizure freedom. Conclusions: Higher expression of GAP-43 proteins associated with longer duration of epilepsy was only observed in patients with FCD II but not in patients with FCD IA or in patients with MTS. Our findings may suggest that GAP-43 may be a potential substrate of progressive epileptogenisis in FCD II. This hypothesis is also supported by the finding that in FCD II group, lower GAP-43 proteins were associated with better surgical outcome.