Abstracts

Rationale: Determining the extent of the epileptogenic zone (EZ) is a significant difficulty in focal cortical dysplasia (FCD). While FCD type II patients often display MRI abnormalities such as gray-white matter blurring, the MRI is normal in the majority of individuals with FCD type I. As a result, FCD surgery is more successful in type II. In recent years, the notion of epileptogenic networks has gained increasing acceptance. Investigating brain connectivity using stereo-electroencephalography (SEEG) signals can help us to map the scope of epileptogenicity in FCD. Effective connectivity, which examines the causal relations among different brain regions, can be computed by cortico-cortical evoked potentials (CCEPs). We apply ictal onset single pulse direct electrical cortical stimulation (iSPES) to pairs of intracranial electrodes to record CCEPs responses on other electrodes. The amplitude and latency of CCEPs characterize the intensity of neuronal excitability, which is linked to the degree of epileptogenicity. We postulate that epileptogenicity is more widespread in FCD type I in comparison to type II.

Methods: We performed CCEPs analysis in 25 patients diagnosed with drug-resistance epilepsy (15 individuals with FCD type I and 10 patients with type II). On average there were 3.6 sites per participant of presumptive ictal onset zone that were stimulated. We computed the root mean square (RMS) of CCEPs responses at three latencies: early (10-60ms after the stimulation), middle (60-250ms), and late (250-600ms). Significant responses were identified using a sign-permutation test. We conducted a two-way statistical analysis to examine the RMS values based on two factors: FCD type and the latency of the response. To consider the effect of confounding variables, we controlled for seizure type and location of epilepsy in separate analyses.

Results: In general, our findings indicated a restricted temporal and spatial response in FCD type II. RMS values of CCEPs were larger in FCD type I in comparison to type II (p < 10^-4) among patients with focal to bilateral tonic-clonic seizures (Figure 1A). Moreover, FCD type I displayed a persistent response in middle and late latencies in contrast to the rapid drop of RMS values in type II. Similar results were observed among participants with temporal lobe epilepsy (Figure 1B). For FCD type II, we compared CCEPs between two surgical outcomes (Engel class I and class II). Results suggested that a better outcome of surgery is associated with more limited responses, both in RMS and latency.

Conclusions: In comparison to FCD type II, the larger RMS values in FCD type I are linked to a higher level of hyperexcitability in this pathological substrate. This discrepancy may underlie the disparities in postsurgical seizure outcomes. The presence of the middle and late components in type I may reflect the involvement of cortico-thalamo-cortical networks. Finally, the restricted response in patients categorized as Engel class I explain the importance of CCEPs recordings for presurgical guidance.

Funding: Please list any funding that was received in support of this abstract.: Research reported in this publication was supported in part by the National Institutes of Health under awards R01NS089212, U01EB023820, and R01EB026299.