Abstracts

Rationale: We aimed to investigate the functional connectivity of the seizure onset zone by low frequency stimulation and cortical-evoked potentials. Methods: Patients who received 1-Hz frequency bipolar stimulation between 2003 and 2014 at prospectively selected contacts were included. The stimulated contacts were classified as: seizure onset (SOZ), within epileptic network (frequent or periodic spiking, and early ictal propagation), or control. Stimulation intensity ranged 10-12 mA (or lower if not tolerated or if auras triggered) and pulse width 0.2-0.3 ms. Evoked responses were reproduced at least once and averaged from 30-110 stimulations. Response contacts were classified as seizure onset zone (SOZ), active interictal, quiet or other. Results: Thirty-nine stimulation sessions in 19 patients were analyzed. Stimulation of epileptic contacts evoked reproducible responses at significantly higher number of contacts than control sites (medians of normalized number of contacts 0.74 vs. 0.32 p 0.0007). These differences were even stronger when normalized to average distance of recorded responses from the stimulation site (medians of normalized values 0.71 vs. 0.15 p 0.0003). The evoked responses after stimulation of the epileptic contacts were seen at further distance from the site of stimulation (medians of normalized distances 0.93 vs. 0.58, p= 0.0004, median absolute values: 58 mm vs. 44 mm). It was 1.6 times more likely to record an evoked response from the seizure onset zone than other contacts after stimulation of a remote control site. Habitual partial seizures or auras were triggered in 26 % of the patients and 33 % of the seizure onset contacts (median stimulation intensity 3.5 mA), but in none of the control or within network contacts. Stimulation of control sites in multifocal or poor surgical outcome cases tended to exhibit higher number of evoked responses at distant sites compared to localizable onsets or good surgical outcome cases (median number of contacts normalized to total number of contacts and average distance 0.5 vs. 0.12, p 0.06). Stimulation of epileptic contact generated responses with longer latencies (medians 48 vs. 38 ms, p< 0.0001), and longer duration (73 vs. 62 ms, p< 0.0001). There was a correlation between the current intensity and normalized number of evoked responses (r = + 0.50, p 0.01) but not with distance (r = + 0.1, p 0.64) Conclusions: The seizure onset zone exhibits enhanced connectivity at distant sites compared to non-epileptic quiet contacts. The evoked responses after stimulation of the seizure onset zone are characterized by longer average latencies and durations. Auras and seizures provoked by low frequency stimulation may be specific to the seizure onset zone. There is a possible correlation between the number of evoked responses from non-epileptic sites and the overall degree of underlying epileptogenicity reflecting perhaps an overall facilitation of synaptic transmission. Stimulation at lower currents may possibly help in identifying distant nodes within the epileptic network.