Abstracts

Rationale: Interictal epileptiform activity (IEA) and seizures have been found in many patients with focal epilepsy to oscillate over patient-specific multiday (termed infradian or multidien) cycles. The source of these cycles is not well understood; they may be due to global influences on cerebral excitability, such as hormonal or behavioral factors; or they could be due to local factors such as localized neurotransmitter changes or emergent properties from focal seizures. Relationships between multiday periodicities from seizure foci in patients with independent seizure onsets, as in bitemporal epilepsy, may help elucidate the source of these rhythms. Cycles that are synchronous between foci might suggest a globally acting source, whereas asynchronous cycles might suggest a local origin. Data from patients with RNS treating two distant foci offer an opportunity to assess this question.

Methods: We reviewed a database of 84 patients across the neurostimulation clinic at the Yale Comprehensive Epilepsy Center to identify subjects with RNS targeting two extrathalamic seizure foci in opposite hemispheres. Of 12 patients identified, 10 had active RNS electrodes in both left and right temporal lobes and 2 had a temporal and a contralateral extratemporal lead. Hourly detection counts from each lead were Morlet wavelet transformed to identify lateralized multiday cycles. Period lengths were calculated for IEA cycles from each focus. For lateralized multiday periods with lengths that were similar within a patient, cycles were determined to be in phase or out of phase by visual analysis of wavelet components. Seizure times were derived from patient-specific seizure surrogates identified from manual review of electrocorticograms. Seizures were determined to have left or right onset depending on the channel with the initial detection. The phase of each seizure within a multiday cycle was calculated by comparison of seizure time to the wavelet components for each cycle. For patients with similar multiday periods between the two hemispheres, lateralized seizure phases were then compared by a non-parametric circular statistical test.

Results: Of 12 patients reviewed, 7 had multiday cycles with similar bilateral periods, 2 had cycles on one side only, and 1 had no cycle. Another 2 patients had two cycles; in each patient, one cycle was bilateral and one was unilateral. No patients were found who had prominent bilateral multiday cycles with clearly and exclusively different period lengths. Among the 9 patients who had at least one multiday cycle with similar periods in both hemispheres, 6 of 9 had bilateral IEA cycles in phase. Seizures could be reliably lateralized and counted in 5 of the 9 patients with similar periods between hemispheres. Of these, none had significantly different seizure phases between left and right.

Conclusions: Our findings suggest patients with bilateral independent seizure foci may have multiday periods evident in only one hemisphere or in both. If cycles do occur bilaterally, the periodicities are synchronous.

Funding: This work was supported by the Swebilius Foundation. We also thank Dr. Maxime Baud for sharing code for analysis of IEA cycles and NeuroPace, Inc. for sharing RNS data.