Association of Early Seizure Prophylaxis With Posttraumatic Seizures and Mortality: A Meta-analysis With Evidence Quality Assessment.

Purpose of the Review: To evaluate the quality of evidence about the association of primary seizure prophylaxis with antiseizure medication (ASM) within 7 days postinjury and the 18- or 24-month epilepsy/late seizure risk or all-cause mortality in adults with new-onset traumatic brain injury (TBI), in addition to early seizure risk. Results: Twenty-three studies met the inclusion criteria (7 randomized and 16 nonrandomized studies). We analyzed 9,202 patients, including 4,390 in the exposed group and 4,812 in the unexposed group (894 in placebo and 3,918 in no ASM groups). There was a moderate to serious bias risk based on our assessment. Within the limitations of existing studies, our data revealed a lower risk for early seizures in the ASM prophylaxis group compared with placebo or no ASM prophylaxis (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.33-0.57, p < 0.00001, I 2 = 3%). We identified high-quality evidence in favor of acute, short-term primary ASM use to prevent early seizures. Early ASM prophylaxis was not associated with a substantial difference in the 18- or 24-month risk of epilepsy/late seizures (RR 1.01, 95% CI 0.61-1.68, p = 0.96, I 2 = 63%) or mortality (RR 1.16, 95% CI 0.89-1.51, p = 0.26, I 2 = 0%). There was no evidence of strong publication bias for each main outcome. The overall quality of evidence was low and moderate for post-TBI epilepsy risk and all-cause mortality, respectively. Summary: Our data suggest that the evidence showing no association between early ASM use and 18- or 24-month epilepsy risk in adults with new-onset TBI was of low quality. The analysis indicated a moderate quality for the evidence showing no effect on all-cause mortality. Therefore, higher-quality evidence is needed as a supplement for stronger recommendations.

Automated Annotation of Epileptiform Burden and Its Association with Outcomes.

OBJECTIVE: This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients. METHODS: A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent >16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6). RESULTS: Peak epileptiform burden was independently associated with poor outcomes (p < 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) <5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290); >10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%. INTERPRETATION: Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Anticonvulsant Primary and Secondary Prophylaxis for Acute Ischemic Stroke Patients: A Decision Analysis.

Background and Purpose: We examined the impact of 3 anticonvulsant prophylaxis strategies on quality-adjusted life-years (QALYs) among patients with an incident acute ischemic stroke. Methods: We created a decision tree to evaluate 3 strategies: (1) long-term primary prophylaxis; (2) short-term secondary prophylaxis after an early seizure with lifetime prophylaxis if persistent or late seizures (LSs) developed; and (3) long-term secondary prophylaxis if either early, late, or persistent seizures developed. The outcome was quality-adjusted life expectancy (QALY). We created 4 base cases to simulate common clinical scenarios: (1) female patient aged 40 years with a 2% or 11% lifetime risk of an LS and a 33% lifetime risk of an adverse drug reaction (ADR); (2) male patient aged 65 years with a 6% or 29% LS risk and 60% ADR risk; (3) male patient aged 50 years with an 18% or 65% LS risk and 33% ADR risk; and (4) female patient aged 80 years with a 29% or 83% LS risk and 80% ADR risk. In sensitivity analyses, we altered the parameters and assumptions. Results: Across all 4 base cases, primary prophylaxis yielded the fewest QALYs when compared with secondary prophylaxis. For example, under scenario 1, strategies 2 and 3 resulted in 7.17 QALYs each, but strategy 1 yielded only 6.91 QALYs. Under scenario 4, strategies 2 and 3 yielded 2.85 QALYs compared with 1.40 QALYs for strategy 1. Under scenarios in which patients had higher ADR risks, strategy 2 led to the most QALYs. Conclusions: Short-term therapy with continued anticonvulsant prophylaxis only after postischemic stroke seizures arise dominates lifetime primary prophylaxis in all scenarios examined. Our findings reinforce the necessity of close follow-up and discontinuation of anticonvulsant seizure prophylaxis started during acute ischemic stroke hospitalization.

Assessment of the Validity of the 2HELPS2B Score for Inpatient Seizure Risk Prediction.

Importance: Seizure risk stratification is needed to boost inpatient seizure detection and to improve continuous electroencephalogram (cEEG) cost-effectiveness. 2HELPS2B can address this need but requires validation. Objective: To use an independent cohort to validate the 2HELPS2B score and develop a practical guide for its use. Design, Setting, and Participants: This multicenter retrospective medical record review analyzed clinical and EEG data from patients 18 years or older with a clinical indication for cEEG and an EEG duration of 12 hours or longer who were receiving consecutive cEEG at 6 centers from January 2012 to January 2019. 2HELPS2B was evaluated with the validation cohort using the mean calibration error (CAL), a measure of the difference between prediction and actual results. A Kaplan-Meier survival analysis was used to determine the duration of EEG monitoring to achieve a seizure risk of less than 5% based on the 2HELPS2B score calculated on first- hour (screening) EEG. Participants undergoing elective epilepsy monitoring and those who had experienced cardiac arrest were excluded. No participants who met the inclusion criteria were excluded. Main Outcomes and Measures: The main outcome was a CAL error of less than 5% in the validation cohort. Results: The study included 2111 participants (median age, 51 years; 1113 men [52.7%]; median EEG duration, 48 hours) and the primary outcome was met with a validation cohort CAL error of 4.0% compared with a CAL of 2.7% in the foundational cohort (P = .13). For the 2HELPS2B score calculated on only the first hour of EEG in those without seizures during that hour, the CAL error remained at less than 5.0% at 4.2% and allowed for stratifying patients into low- (2HELPS2B = 0; <5% risk of seizures), medium- (2HELPS2B = 1; 12% risk of seizures), and high-risk (2HELPS2B, ≥2; risk of seizures, >25%) groups. Each of the categories had an associated minimum recommended duration of EEG monitoring to achieve at least a less than 5% risk of seizures, a 2HELPS2B score of 0 at 1-hour screening EEG, a 2HELPS2B score of 1 at 12 hours, and a 2HELPS2B score of 2 or greater at 24 hours. Conclusions and Relevance: In this study, 2HELPS2B was validated as a clinical tool to aid in seizure detection, clinical communication, and cEEG use in hospitalized patients. In patients without prior clinical seizures, a screening 1-hour EEG that showed no epileptiform findings was an adequate screen. In patients with any highly epileptiform EEG patterns during the first hour of EEG (ie, a 2HELPS2B score of ≥2), at least 24 hours of recording is recommended.