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

難治てんかん焦点の新しいバイオマーカー「発作時DC電位」 --国内5施設の共同研究での世界初の成果--. 京都大学プレスリリース. 2022-09-05.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 (icDCs; below 1 Hz) and ictal high-frequency oscillations (icHFOs; 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 icDCs which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG datasets recorded with a longer time constant of 10 sec using an alternate current amplifier. 61 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 icDCs and icHFOs 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 icDCs and icHFOs. Additionally, we examined whether the resection ratio of the core electrodes of icDCs and icHFOs independently correlated with favorable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. icDCs were detected in the seizure-onset zone more frequently than icHFOs among both patients (92% vs. 71%) and seizures (86% vs. 62%). Additionally, icDCs significantly preceded icHFOs in patients exhibiting both biomarkers, and icDCs occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for icDCs and icHFOs (39%) at the electrode level, complete resection of the core area of icDCs significantly correlated with favorable outcomes, similar to icHFO outcomes. Our results provide a proof of concept that the independent significance of icDCs from icHFOs should be considered as reliable biomarkers to achieve favorable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of icDCs and icHFOs 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

Epileptic network of hypothalamic hamartoma: An EEG-fMRI study.

To investigate the brain networks involved in epileptogenesis/encephalopathy associated with hypothalamic hamartoma (HH) by EEG with functional MRI (EEG-fMRI), and evaluate its efficacy in locating the HH interface in comparison with subtraction ictal SPECT coregistered to MRI (SISCOM). Eight HH patients underwent EEG-fMRI. All had gelastic seizures (GS) and 7 developed other seizure types. Using a general linear model, spike-related activation/deactivation was analyzed individually by applying a hemodynamic response function before, at, and after spike onset (time-shift model = −8–+4 s). Group analysis was also performed. The sensitivity of EEG-fMRI in identifying the HH interface was compared with SISCOM in HH patients having unilateral hypothalamic attachment. EEG-fMRI revealed activation and/or deactivation in subcortical structures and neocortices in all patients. 6/8 patients showed activation in or around the hypothalamus with the HH interface with time-shift model before spike onset. Group analysis showed common activation in the ipsilateral hypothalamus, brainstem tegmentum, and contralateral cerebellum. Deactivation occurred in the default mode network (DMN) and bilateral hippocampi. Among 5 patients with unilateral hypothalamic attachment, activation in or around the ipsilateral hypothalamus was seen in 3 using EEG-fMRI, whereas hyperperfusion was seen in 1 by SISCOM. Group analysis of this preliminary study may suggest that the commonly activated subcortical network is related to generation of GS and that frequent spikes lead to deactivation of the DMN and hippocampi, and eventually to a form of epileptic encephalopathy. Inter-individual variance in neocortex activation explains various seizure types among patients. EEG-fMRI enhances sensitivity in detecting the HH interface compared with SISCOM