High-rate leading spikes in propagating spike sequences predict seizure outcome in surgical patients with temporal lobe epilepsy.

Abstract

Inter-ictal spikes aid in the diagnosis of epilepsy and in planning surgery of medication-resistant epilepsy. However, the localizing information from spikes can be unreliable because spikes can propagate, and the burden of spikes, often assessed as a rate, does not always correlate with the seizure onset zone or seizure outcome. Recent work indicates identifying where spikes regularly emerge and spread could localize the seizure network. Thus, the current study sought to better understand where and how rates of single and coupled spikes, and especially brain regions with high-rate and leading spike of a propagating sequence, informs the extent of the seizure network. In 37 patients with medication-resistant temporal lobe seizures, who had surgery to treat their seizure disorder, an algorithm detected spikes in the pre-surgical depth inter-ictal EEG. A separate algorithm detected spike propagation sequences and identified the location of leading and downstream spikes in each sequence. We analysed the rate and power of single spikes on each electrode and coupled spikes between pairs of electrodes, and the proportion of sites with high-rate, leading spikes in relation to the seizure onset zone of patients seizure free (n = 19) and those with continuing seizures (n = 18). We found increased rates of single spikes in mesial temporal seizure onset zone (ANOVA, P < 0.001, η2 = 0.138), and increased rates of coupled spikes within, but not between, mesial-, lateral- and extra-temporal seizure onset zone of patients with continuing seizures (P < 0.001; η2 = 0.195, 0.113 and 0.102, respectively). In these same patients, there was a higher proportion of brain regions with high-rate leaders, and each sequence contained a greater number of spikes that propagated with a higher efficiency over a longer distance outside the seizure onset zone than patients seizure free (Wilcoxon, P = 0.0172). The proportion of high-rate leaders in and outside the seizure onset zone could predict seizure outcome with area under curve = 0.699, but not rates of single or coupled spikes (0.514 and 0.566). Rates of coupled spikes to a greater extent than single spikes localize the seizure onset zone and provide evidence for inter-ictal functional segregation, which could be an adaptation to avert seizures. Spike rates, however, have little value in predicting seizure outcome. High-rate spike sites leading propagation could represent sources of spikes that are important components of an efficient seizure network beyond the clinical seizure onset zone, and like the seizure onset zone these, too, need to be removed, disconnected or stimulated to increase the likelihood for seizure control.