Abstracts

Rationale: Intraoperative electrocorticography (ioECoG) can help to delineate epileptogenic tissue during epilepsy surgery and improve seizure outcome. High frequency oscillations (HFOs) in ioECoG are promising biomarkers for epileptogenic tissue and are closely related to epileptogenesis. The exact mechanism of HFO generation is still being discussed. They are thought to be generated by hyperexcitable neurons. Neuronal excitability can be promoted by neuroinflammation, another key player in epileptogenesis. We investigate the relation between HFOs and inflammation in tumor-related epilepsy to improve the understanding behind HFO generation mechanism and epileptogenesis (figure 1). This is the first study to directly compare high frequency oscillations and inflammatory markers that contribute to epileptogenesis.

Methods: We identified HFOs (ripples 80-250Hz, fast ripples 250-500Hz) in the ioECoG of 32 patients with low-grade epilepsy-associated tumors. Localization of recorded HFOs was classified based on MRI reconstructions being: in the tumor, in the resected non-tumorous area and outside the resected area. We investigated if HFOs were related to the inflammatory markers in the tumor or the peritumoral tissues. We analyzed the following inflammatory markers which are known to contribute to epileptogenesis: activated microglia, CD3-positive T-cells, interleukin 1-beta (IL1β), toll-like receptor 4 (TLR4) and high mobility group box 1 protein (HMGB1).

Results: 1326 bipolar electrodes in ioECoG were analyzed. Ripples were present in 30 patients and fast ripples in 10 patients. Tumors that generated ripples were infiltrated by more CD3-positive T-cells than tumors without ripples. The more the concomitant IL1β/HMGB1/TLR4 pathways were active, the higher the ripple rate. We found no correlations between fast ripple rates and inflammatory markers.

Conclusions: Ripple rate in ioECoG is associated with the number of T-cells in the tumor tissue and the IL1β/HMGB1/TLR4 pathway activity in the peritumoral tissue. Our findings support that ripple generation and spread may be associated with synchronized fast firing of hyperexcitable neurons due to neuroinflammation. This study provides arguments for further investigations in HFOs and inflammation.

Funding: Please list any funding that was received in support of this abstract.: This work was supported by the European Research Council starting grant 803880 and N.v.K. was supported by the Dutch Brain Foundation (2013- 139).