Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery

Mitsuyoshi Nakatani; Morito Inouchi; Masako Daifu-Kobayashi; Tomohiko Murai; Jumpei Togawa; Shunsuke Kajikawa; Katsuya Kobayashi; Takefumi Hitomi; Takeharu Kunieda; Satoka Hashimoto; Motoki Inaji; Hiroshi Shirozu; Kyoko Kanazawa; Masaki Iwasaki; Naotaka Usui; Yushi Inoue; Taketoshi Maehara; Akio Ikeda

doi:10.1093/braincomms/fcac222

Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery

Brain Commun. 2022 Sep 3;4(5):fcac222. doi: 10.1093/braincomms/fcac222. eCollection 2022.

Authors

Mitsuyoshi Nakatani¹, Morito Inouchi^{2

3}, Masako Daifu-Kobayashi¹, Tomohiko Murai¹, Jumpei Togawa¹, Shunsuke Kajikawa¹, Katsuya Kobayashi¹, Takefumi Hitomi⁴, Takeharu Kunieda^{5

6}, Satoka Hashimoto⁷, Motoki Inaji⁷, Hiroshi Shirozu⁸, Kyoko Kanazawa⁹, Masaki Iwasaki¹⁰, Naotaka Usui¹¹, Yushi Inoue¹², Taketoshi Maehara⁷, Akio Ikeda²

Affiliations

¹ Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
² Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
³ Department of Neurology, Kyoto City Hospital, 1-2 Mibuhigashitakadacho, Nakagyo-ku, Kyoto 604-8845, Japan.
⁴ Department of Laboratory Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
⁵ Department of Neurosurgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.
⁶ Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
⁷ Department of Functional Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁸ Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, 1-14-1 Masago, Nishi-ku, Niigata 950-2085, Japan.
⁹ Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi-cho, Kodaira-shi, Tokyo 187-8551, Japan.
¹⁰ Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi-cho, Kodaira-shi, Tokyo 187-8551, Japan.
¹¹ Department of Neurosurgery, Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 886, Aoi-ku, Shizuoka 420-8688, Japan.
¹² Department of Psychiatry, Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 886, Aoi-ku, Shizuoka 420-8688, Japan.

Abstract

Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (below 1 Hz) and ictal high-frequency oscillations (above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly ictal direct-current shifts which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG data sets recorded with a longer time constant of 10 s using an alternate current amplifier. Sixty-one patients (15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy) who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both ictal direct-current shifts and ictal high-frequency oscillations were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both ictal direct-current shifts and ictal high-frequency oscillations. Additionally, we examined whether the resection ratio of the core electrodes of ictal direct-current shifts and ictal high-frequency oscillations independently correlated with favourable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. Ictal direct-current shifts were detected in the seizure-onset zone more frequently than ictal high-frequency oscillations among both patients (92% versus 71%) and seizures (86% versus 62%). Additionally, ictal direct-current shifts significantly preceded ictal high-frequency oscillations in patients exhibiting both biomarkers, and ictal direct-current shifts occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for ictal direct-current shifts and ictal high-frequency oscillations (39%) at the electrode level, complete resection of the core area of ictal direct-current shifts significantly correlated with favourable outcomes, similar to ictal high-frequency oscillation outcomes. Our results provide a proof of concept that the independent significance of ictal direct-current shifts from ictal high-frequency oscillations should be considered as reliable biomarkers to achieve favourable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of ictal direct-current shifts and ictal high-frequency oscillations may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels.

Keywords: ictal direct-current (DC) shifts; ictal high-frequency oscillations (HFOs); intractable focal epilepsy; presurgical evaluation; surgical outcome.