Quantitative Electrocorticographic Biomarkers of Clinical Outcomes in Mesial Temporal Lobe Epileptic Patients Treated With the RNS System Desai N, Tchen T, Morrell MJ. Clinical Neurophysiology. 2019;130:1364-1374. doi:10.1016/j.clinph.2019.05.017. OBJECTIVES: Find interictal electrocorticographic (ECoG) biomarkers of clinical outcomes in mesiotemporal lobe (MTL) epilepsy patients. METHODS: In the NeuroPace RNS System clinical trials with 256 patients, 20 MTL patients with the most reduction in clinical seizures at year 7 compared to baseline (upper response quartile: 96.5% median change) and 20 with the least reduction in clinical seizures (lower response quartile: 17.4% median change) were evaluated. Clinical and interictal ECoG features from the 2 response quartiles were compared. RESULTS: Demographic and clinical features were similar in the upper and lower response quartiles. Interictal spike rate (ISR) was substantially lower (P <.0001) in the upper quartile patients, while normalized θ (4-8 Hz) and normalized γ (>25 Hz) were also different (P <.05) between the 2 response quartiles. Interictal spike rate was positively correlated (P <.05) with clinical seizure rates in 71% of the channels analyzed. Electrocorticographic records captured during months with no clinical seizures had the lowest ISR. CONCLUSIONS: Interictal spike rate is a strong differentiator of clinical response in MTL patients. Normalized θ and γ also differentiates clinical response. SIGNIFICANCE: In MTL patients, the ISR along with spectral power computed from chronic ambulatory baseline ECoGs may serve as biomarkers of clinical outcomes and maybe used as treatment end points.

Sleep Disruption in Epilepsy: Ictal and Interictal Epileptic Activity Matter Peter-Derex L, Klimes P, Latreille V, et al. Ann Neurol. 2020;88(5):907-920. doi:10.1002/ana.25884. PMID: 32833279. Objective: Disturbed sleep is common in epilepsy. The direct influence of nocturnal epileptic activity on sleep fragmentation remains poorly understood. Stereo-electroencephalography paired with polysomnography is the ideal tool to study this relationship. We investigated whether sleep-related epileptic activity is associated with sleep disruption. Methods: We visually marked sleep stages, arousals, seizures, and epileptic bursts in 36 patients with focal drug resistant epilepsy who underwent combined stereo-electroencephalography/polysomnography during presurgical evaluation. Epileptic spikes were detected automatically. Spike and burst indices (n/sec/channel) were computed across four 3-second time windows (baseline sleep, prearousal, arousal, and postarousal). Sleep stage and anatomic localization were tested as modulating factors. We assessed the intra-arousal dynamics of spikes and their relationship with the slow-wave component of nonrapid eye movement sleep (NR) arousals. Results: The vast majority of sleep-related seizures (82.4%; 76.5% asymptomatic) were followed by awakenings or arousals. The epileptic burst index increased significantly before arousals as compared to baseline and postarousal, irrespective of sleep stage or brain area. A similar prearousal increase was observed for the spike index in NR stage 2 and rapid eye movement sleep. In addition, the spike index increased during the arousal itself in neocortical channels and was strongly correlated with the slow-wave component of NR arousals (r = 0.99, P <.0001). Interpretation: Sleep fragmentation in focal drug-resistant epilepsy is associated with ictal and interictal epileptic activity. The increase in interictal epileptic activity before arousals suggests its participation in sleep disruption. An additional increase in the spike rate during arousals may result from a sleep–wake boundary instability, suggesting a bidirectional relationship.

Intraoperative Electrocorticography During Laser-Interstitial Thermal Therapy Predicts Seizure Outcome in Mesial Temporal Lobe Epilepsy Chen, B, Grewal SS, Middlebrooks EH, Tatum WO, Ritaccio AL, Sirven JI, Freqund BE, Feyissa AM. Clin Neurophysiol. 2023;146:118-123. doi:10.1016/j.clinph.2022.12.003 Background and Objectives: Magnetic resonance-guided laser interstitial thermal therapy (MRLiTT) for treating temporal lobe epilepsy has recently gained popularity. We aimed to investigate the predictive value of pre-and post-MRLiTT epileptiform discharges (EDs) on intraoperative electrocorticography (iECoG) in seizure outcomes for patients with mesial temporal lobe epilepsy (mTLE). Methods: We conducted a pilot, prospective single-center cohort study on seven consecutive patients with mTLE that underwent MRLiTT. Pre- and post-MRLiTT iECoG was performed using a 1×8 contact depth electrode along the same trajectory used for the laser catheter. Findings: The responders had a robust reduction in ED frequency compared to pre-MRLiTT iECoG (86% vs 13%, p < 0.01). Clinical characteristics, including risk factors for epilepsy, duration of epilepsy, presence of mesial temporal lobe sclerosis, prior intracranial monitoring, the absolute frequency of pre- or post-MRLiTT EDs, and ablation volume were not significantly associated with responder status. Discussion: This is the first demonstration that intraoperative reduction in EDs during mesial temporal lobe MRLiTT may potentially predict seizure outcomes and may serve as an intraoperative biomarker for satisfactory ablation. However, larger prospective studies are needed to confirm our findings and evaluate the utility of iECoG during MRLiTT.

Localization Value of Subclinical Seizures on Scalp Video-EEG in Epilepsy Presurgical Evaluation Wang Shan, Wang ZI, Tangy Y, et al. Epilepsia. 2019;60(1):2477-2485. doi:10.1111/epi.16383. Objective: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. Methods: We included 123 consecutive patients who had SCSs and CSs during scalp VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into 5 categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. Results: Sixty-nine (56.1%) patients had seizure-free outcome at 1-year follow-up. In 68 (55.3%) patients, the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1 year (P =.020) and 2-year follow-up (P =.040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. Significance: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.

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Effect of Levetiracetam Use Duration on Overall Survival of Isocitrate Dehydrogenase Wild-Type Glioblastoma in Adults: An Observational Study Pallud J, Huberfeld G, Dezamis E, et al. Neurology. 2022;98(2):e125-e140. doi:10.1212/WNL.0000000000013005. Background and Objectives: The association between levetiracetam and survival with isocitrate dehydrogenase (IDH) wild type glioblastomas is controversial. We investigated whether the duration of levetiracetam use during the standard chemoradiation protocol affects overall survival (OS) of patients with IDH wild-type glioblastoma. Methods: In this observational single-institution cohort study (2010-2018), inclusion criteria were (1) age=18 years; (2) newly diagnosed supratentorial tumor; (3) histomolecular diagnosis of IDH wild-type glioblastoma; and (4) standard chemoradiation protocol. To assess the survival benefit of levetiracetam use during the standard chemoradiation protocol (whole duration, part time, and never subgroups), a Cox proportional hazard model was constructed. We performed a case-matched analysis (1:1) between patients with levetiracetam use during the whole du ration of the standard chemoradiation protocol and patients with levetiracetam use part time or never according to the following criteria: sex, age, epileptic seizures at diagnosis, Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) class, tumor location, preoperative volume, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Patients with unavailable O6-methylguanine-DNA methyltransferase promoter methylation status (48.5%) were excluded. Results: A total of 460 patients were included. The median OS was longer in the 116 patients with levetiracetam use during the whole duration of the standard chemoradiation protocol (21.0 months; 95% confidence interval [CI] 17.2-24.0) than in the 126 patients with part-time levetiracetam use (16.8 months; 95% CI 12.4-19.0) and in the 218 patients who never received levetiracetam (16.0 months; 95% CI 15.5-19.4; P =.027). Levetiracetam use during the whole duration of the standard chemoradiation protocol (adjusted hazard ratio [aHR].69; 95% CI.52-.93; P =.014), MGMT promoter methylation (aHR.53; 95% CI.39-.71; P <.001), and gross total tumor resection (aHR.57; 95% CI.44-.74; P <.001) were independent predictors of longer OS. After case matching (n = 54 per group), a longer OS was found for levetiracetam use during the whole duration of the standard chemoradiation protocol (hazard ratio.63; 95% CI.42-.94; P =.023). Discussion: Levetiracetam use during the whole standard chemoradiation protocol possibly improves OS of patients with IDH wild-type glioblastoma. It should be considered in the antitumor strategy of future multicentric trials. Classification of evidence: This study provides Class III evidence that in individuals with IDH wild-type glioblastoma, levetiracetam use throughout the duration of standard chemotherapy is associated with longer median OS.

Serious Cardiac Arrhythmias Detected by Subcutaneous Long-Term Cardiac Monitors in Patients With Drug-Resistant Epilepsy Sivathamboo S, Liu Z, Sutherland F, Minato E, Casillas-Espinosa P, Jones NC, Todaro M, Seneviratne U, Cahill V, Yerra R, French C, Nicolo J-P, Perucca P, Kwan P, Sparks P, O’Brien TJ. Neurology. 2022;98(19):e1923-e1932. doi:10.1212/WNL.0000000000200173 Background and Objectives: Epilepsy is associated with an increased risk of cardiovascular disease and premature mortality, including sudden unexpected death in epilepsy (SUDEP). Serious cardiac arrythmias might go undetected in routine epilepsy and cardiac investigations. Methods: This prospective cohort study aimed to detect cardiac arrhythmias in patients with chronic drug-resistant epilepsy (≥5 years duration) using subcutaneous cardiac monitors for a minimum follow-up duration of 12 months. Participants with known cardiovascular disease or those with abnormal 12-lead ECGs were excluded. The device was programmed to automatically record episodes of tachycardia ≥140 beats per minute (bpm), bradycardia 40 bpm for ≥3 seconds, or asystole ≥3 seconds. Findings: Thirty-one patients underwent subcutaneous cardiac monitoring for a median recording duration of 2.2 years (range 0.5-4.2). During this time, 28 patients (90.3%) had episodes of sustained (≥30 seconds) sinus tachycardia, 8/31 (25.8%) had sinus bradycardia, and 3 (9.7%) had asystole. Three patients (9.7%) had serious cardiac arrhythmias requiring additional cardiac interventions. Among them, 2 patients had prolonged sinus arrest and ventricular asystole (>6 seconds), leading to pacemaker insertion in one, and another patient with epileptic encephalopathy had multiple episodes of recurrent nonsustained polymorphic ventricular tachycardia and bundle branch conduction abnormalities. The time to first detection of a clinically significant cardiac arrhythmia ranged between 1.2 and 26.9 months following cardiac monitor insertion. Discussion: Implantable cardiac monitors detected a high incidence of clinically significant cardiac arrhythmias in patients with chronic drug-resistant epilepsy, which may contribute to the incidence of premature mortality, including SUDEP.

UNLABELLED: Removing High-Frequency Oscillations: A Prospective Multicenter Study on Seizure Outcome Jacobs J, Wu JY, Perucca P, et al. Neurology. 2018;91(11):e1040-e1052. OBJECTIVE: To evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial. METHODS: We hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue, while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient. RESULTS: There was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 (67%) patients. Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication. CONCLUSIONS: On an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.