Alcohol for seizure induction in the epilepsy monitoring unit.

RATIONALE: Seizure induction techniques are used in the epilepsy monitoring unit (EMU) to increase diagnostic yield and reduce length of stay. There are insufficient data on the efficacy of alcohol as an induction technique. METHODS: We performed a retrospective cohort study using six years of EMU data at our institution. We compared cases who received alcohol for seizure induction to matched controls who did not. The groups were matched on the following variables: age, reason for admission, length of stay, number of antiseizure medications (ASM) at admission, whether ASMs were tapered during admission, and presence of interictal epileptiform discharges. We used both propensity score and exact matching strategies. We compared the likelihood of epileptic seizures and nonepileptic events in cases versus controls using Kaplan-Meier time-to-event analysis, as well as odds ratios for these outcomes occurring at any time during the admission. RESULTS: We analyzed 256 cases who received alcohol (median dose 2.5 standard drinks) and 256 propensity score-matched controls. Cases who received alcohol were no more likely than controls to have an epileptic seizure (X2(1) = 0.01, p = 0.93) or nonepileptic event (X2(1) = 2.1, p = 0.14) in the first 48 h after alcohol administration. For the admission overall, cases were no more likely to have an epileptic seizure (OR 0.89, 95 % CI 0.61-1.28, p = 0.58), nonepileptic event (OR 0.97, CI 0.62-1.53, p = 1.00), nor require rescue benzodiazepine (OR 0.63, CI 0.35-1.12, p = 0.15). Stratified analyses revealed no increased risk of epileptic seizure in any subgroups. Sensitivity analysis using exact matching showed that results were robust to matching strategy. CONCLUSIONS: Alcohol was not an effective induction technique in the EMU. This finding has implications for counseling patients with epilepsy about the risks of drinking alcohol in moderation in their daily lives.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Quantifying trial-by-trial variability during cortico-cortical evoked potential mapping of epileptogenic tissue.

OBJECTIVE: Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations. METHODS: We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1 Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates. RESULTS: We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ. SIGNIFICANCE: These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1 Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.

Quantitative artifact reduction and pharmacologic paralysis improve detection of EEG epileptiform activity in critically ill patients.

OBJECTIVE: Epileptiform activity is common in critically ill patients, but movement-related artifacts-including electromyography (EMG) and myoclonus-can obscure EEG, limiting detection of epileptiform activity. We sought to determine the ability of pharmacologic paralysis and quantitative artifact reduction (AR) to improve epileptiform discharge detection. METHODS: Retrospective analysis of patients who underwent continuous EEG monitoring with pharmacologic paralysis. Four reviewers read each patient's EEG pre- and post- both paralysis and AR, and indicated the presence of epileptiform discharges. We compared the interrater reliability (IRR) of identifying discharges at baseline, post-AR, and post-paralysis, and compared the performance of AR and paralysis according to artifact type. RESULTS: IRR of identifying epileptiform discharges at baseline was slight (N = 30; κ = 0.10) with a trend toward increase post-AR (κ = 0.26, p = 0.053) and a significant increase post-paralysis (κ = 0.51, p = 0.001). AR was as effective as paralysis at improving IRR of identifying discharges in those with high EMG artifact (N = 15; post-AR κ = 0.63, p = 0.009; post-paralysis κ = 0.62, p = 0.006) but not with primarily myoclonus artifact (N = 15). CONCLUSIONS: Paralysis improves detection of epileptiform activity in critically ill patients when movement-related artifact obscures EEG features. AR improves detection as much as paralysis when EMG artifact is high, but is ineffective when the primary source of artifact is myoclonus. SIGNIFICANCE: In the appropriate setting, both AR and paralysis facilitate identification of epileptiform activity in critically ill patients.

Using Generalized Polyspike Train to Predict Drug-Resistant Idiopathic Generalized Epilepsy.

INTRODUCTION: The authors tested the hypothesis that the EEG feature generalized polyspike train (GPT) is associated with drug-resistant idiopathic generalized epilepsy (IGE). METHODS: The authors conducted a single-center case-control study of patients with IGE who had outpatient EEGs performed between 2016 and 2020. The authors classified patients as drug-resistant or drug-responsive based on clinical review and in a masked manner reviewed EEG data for the presence and timing of GPT (a burst of generalized rhythmic spikes lasting less than 1 second) and other EEG features. A relationship between GPT and drug resistance was tested before and after controlling for EEG duration. The EEG duration needed to observe GPT was also calculated. RESULTS: One hundred three patients were included (70% drug-responsive and 30% drug-resistant patients). Generalized polyspike train was more prevalent in drug-resistant IGE (odds ratio, 3.8; 95% confidence interval, 1.3-11.4; P = 0.02). This finding persisted when controlling for EEG duration both with stratification and with survival analysis. A median of 6.5 hours (interquartile range, 0.5-12.7 hours) of EEG recording was required to capture the first occurrence of GPT. CONCLUSIONS: The findings support the hypothesis that GPT is associated with drug-resistant IGE. Prolonged EEG recording is required to identify this feature. Thus, >24-hour EEG recording early in the evaluation of patients with IGE may facilitate prognostication.

Neuroanatomical evidence for a putative autocrine/paracrine signaling system involving nicotinic acetylcholine receptors, purinergic receptors, and nitric oxide synthase in the airways.

Nicotine in tobacco smoke is thought to stimulate sensory nerve fibers by receptors that are located on airway epithelial cells and on terminal branches of C-fiber afferents, but the exact neurochemical substrate that mediates the sensory effects of nicotine associated with cigarette smoking is not clear. ATP and nitric oxide (NO) have both been implicated in lung responsiveness to airborne chemicals such as nicotine. However, the neuroanatomical and functional relationships between nicotinic acetylcholine receptors (nAChRs), purinergic signaling, and NO are not known, and the main source of NO in the airways is not clear. In the present study, we performed RT-PCR to confirm the presence of mRNA for all three isoforms of nitric oxide synthase (NOS), neuronal (n-NOS), endothelial (e-NOS), and inducible (i-NOS), in the lung. Sequential double labeling was performed to assess the site of expression of the different NOS isoforms with respect to nAChRs and purinergic receptors (P2X3R) of the intrapulmonary airways. RT-PCR confirmed the presence of n-NOS, e-NOS, and i-NOS in the lung, and immunohistochemical studies verified their expression by epithelial cells at all levels of the intrapulmonary airways, including the terminal and respiratory bronchioles. Sequential double labeling demonstrated coexpression of n-NOS and/or i-NOS with nAChR- and P2X3R-expressing cells. These neuroanatomical findings suggest that bronchial epithelial cells may be a primary source of NO in the intrapulmonary airways and that the production and release of NO may be regulated by an autocrine/paracrine signaling system involving nAChRs and P2X3Rs.