Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies.

OBJECTIVE: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. METHODS: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. RESULTS: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10-3, 95%CI = -16.08 to -8.58 × 10-3 (µg/mL)/(mg/day), p < 0.001, MD = -7.16 (µg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (µg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10-3 (µg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10-3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. CONCLUSIONS: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series.

BACKGROUND: Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation. OBJECTIVE: In this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation. METHODS: We present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24 h of ketamine administration. RESULTS: A total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26-72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%) cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to a long term acute care hospital, and one patient to hospice. CONCLUSION: The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chart review.

Predicting seizure clustering in the epilepsy monitoring unit: A multivariable analysis.

INTRODUCTION: Seizure clustering, is the most frequently reported adverse event in epilepsy monitoring unit (EMU) safety studies which, can also potentiate other adverse events, such as falls, status epilepticus, and increased length of stay. The purpose of this study is to determine variables associated with increased risk of seizure clustering among patients admitted to the EMU. METHODS: A retrospective review of patients admitted to the EMU over a two-year period was completed. Data collected included patient demographics, types of epilepsy, seizure frequency, anti-seizure medications (ASMs) and hospital and EMU course including incidence of seizure clustering. RESULTS: Two hundred seven patients were included in our study; of these, ninety patients experienced two or more seizures in a 24-hour period (24SC), and 68 patients experienced two or more seizures in a 4-hour period (4SC). Logistic regression analysis associated the absence of long-acting ASM with increased clustering within the 4SC group (p = 0.038). For every additional ASM taken by a patient at home, the odds of seizure clustering increased by 81% in the 4SC group (p = 0.009) and by 61% in the 24SC group (p = 0.022). In addition, patients with a diagnosis of temporal lobe epilepsy had some association with clustering in the 24SC group (p = 0.061). CONCLUSION: Our data showed that long-acting ASMs can be protective against seizure clustering. Furthermore, patients with temporal lobe epilepsy, and those on increased numbers of ASMs, were more likely to experience seizure clustering when undergoing medication withdrawal during an EMU evaluation.

Dobbs Versus Jackson: Epilepsy, Reproductive Health, and Abortion.

On June 24, 2022, Dobbs vs Jackson Women's Health Organization was decided by the Supreme Court effectively overturning the former precedent of Roe v. Wade. This ruling has direct consequences for the care of persons with epilepsy of childbearing potential. Now more than ever we need to provide informed and comprehensive care to our patients with epilepsy who are particularly vulnerable to the impact of this legislation on their reproductive decision-making. Important areas to understand include (1) the current state of affairs on abortion in the United States; (2) contraception options, their effectiveness, and interactions with anti-seizure medications (ASM); (3) teratogenic effects and adverse neurocognitive outcomes of ASMs; (4) folic acid supplementation; (5) the effect on perinatal and pediatric care; and (6) unique issues related to people of color.

Understanding the Influence of Hospital Volume on Inpatient Outcomes Following Hospitalization for Status Epilepticus.

BACKGROUND: Prior studies show hospital admission volume to be associated with poor outcomes following elective procedures and inpatient medical hospitalizations. However, it is unknown whether hospital volume impacts Inpatient outcomes for status epilepticus (SE) hospitalizations. In this study, we aimed to assess the impact of hospital volume on the outcome of patients with SE and related inpatient medical complications. METHODS: The 2005 to 2013 National Inpatient Sample database was queried using International Classification of Diseases 9th Edition diagnosis code 345.3 to identify patients undergoing acute hospitalization for SE. The National Inpatient Sample hospital identifier was used as a unique facility identifier to calculate the average volume of patients with SE seen in a year. The study cohort was divided into three groups: low volume (0-7 patients with SE per year), medium volume (8-22 patients with SE per year), and high volume (> 22 patients with SE per year). Multivariate logistic regression analyses were used to assess whether medium or high hospital volume had lower rates of inpatient medical complications compared with low-volume hospitals. RESULTS: A total of 137,410 patients with SE were included in the analysis. Most patients (n = 50,939; 37%) were treated in a low-volume hospital, 31% (n = 42,724) were treated in a medium-volume facility, and 18% (n = 25,207) were treated in a high-volume hospital. Patients undergoing treatment at medium-volume hospitals (vs. low-volume hospitals) had higher odds of pulmonary complications (odds ratio [OR] 1.18 [95% confidence interval {CI} 1.12-1.25]; p < 0.001), sepsis (OR 1.24 [95% CI 1.08-1.43] p = 0.002), and length of stay (OR 1.13 [95% CI 1.0 -1.19] p < 0.001). High-volume hospitals had significantly higher odds of urinary tract infections (OR 1.21 [95% CI 1.11-1.33] p < 0.001), pulmonary complications (OR 1.19 [95% CI 1.10-1.28], p < 0.001), thrombosis (OR 2.13 [95% CI 1.44-3.14], p < 0.001), and renal complications (OR 1.21 [95% CI 1.07-1.37], p = 0.002). In addition, high-volume hospitals had lower odds of metabolic (OR 0.81 [95% CI 0.72-0.91], p < 0.001), neurological complications (OR 0.80 [95% CI 0.69-0.93], p = 0.004), and disposition to a facility (OR 0.89 [95% CI 0.82-0.96], p < 0.001) compared with lower-volume hospitals. CONCLUSIONS: Our study demonstrates certain associations between hospital volume and outcomes for SE hospitalizations. Further studies using more granular data about the type, severity, and duration of SE and types of treatment are warranted to better understand how hospital volume may impact care and prognosis of patients.

Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model.

BACKGROUND: In this study, we identify factors associated with ketamine success in the treatment of refractory status epilepticus (SE). We also evaluate for adverse events including systemic and cerebral hemodynamic stability and fluid volume overload. METHODS: In this retrospective, large, single-center, observational study over a 10-year period, 879 consecutive patients receiving intravenous (IV) ketamine were reviewed, and 81 patients were identified as receiving IV ketamine for the treatment of SE. Descriptive analysis was done to determine treatment response and adverse events in patients receiving IV ketamine for SE. Multivariable logistic regression analyses were fitted to determine prediction models for seizure cessation. RESULTS: Permanent cessation of SE was achieved in 49 of 81 (60.5%) of patients for whom ketamine was part of the treatment plan. Of those, 36 (44.4%) were attributed to ketamine as the last drug used (ketamine-associated cessation [AC]). Prior history of epilepsy had an odds ratio of 3.19 (confidence interval 0.83-12.67, p = 0.09) associated with efficacious medication response. Increased latency to ketamine was associated with cessation of SE specifically in patients in the AC group (p = 0.077). Longer SE duration (p = 0.04), administration of ketamine loading dose (bolus; p = 0.03), and anoxia (p = 0.007) were negatively associated with AC. Administration of ketamine loading dose (p = 0.02) and anoxia (p = 0.009) were negatively associated with overall SE cessation. There was no significant impact of ketamine on cerebral hemodynamics, but evidence of fluid volume overload was seen (28.4% of patients). CONCLUSIONS: Our cohort is a large observational study showing a high success rate of permanent cessation of SE after the addition of ketamine. Using multivariable analysis, we demonstrate a significant association with seizure cessation in patients with prior history of epilepsy and those with prolonged latency to ketamine initiation. Furthermore, we describe the impact of fluid volume overload as an anticipated complication with ketamine use.

NeuroMeasures-Implementation of a Web-Based, Real-Time Quality Metric Tool to Improve Provider Practices in an Epilepsy Clinic.

Background and Objectives: The retrospective nature of most available epilepsy quality improvement (QI) tools focuses on changing health care provider (HCP) clinical habits and documentation practices rather than a focus on real-time patient interventions. Furthermore, patient-reported outcome data are often not available to determine the efficacy of these tools. Our primary objective was to demonstrate the improvement of HCPs' documentation and review of epilepsy quality measures (EQMs) during the patient visit with the implementation of a novel web application, NeuroMeasures. Our secondary objective was to improve the percentage of point-of-care counseling and interventions based on quality measures during the patient encounter based on the results of the NeuroMeasures tool. Methods: Our QI study focused on comparing a preintervention and postintervention cohort of patients with epilepsy (PWE) before the implementation of NeuroMeasures, a web-based application that takes a self-guided patient survey through self-scoring algorithms focused on the American Academy of Neurology (AAN)'s 2017 EQMs. This e-tool then provides the HCP a tool to directly review the EQMs highlighted and perform any necessary counseling or interventions at the point-of-care visit. After intervention, EQMs were gained from the review of the NeuroMeasures HCP quality measures tool and a chart review for physician documentation. Patients with language barriers and severe cognitive disabilities were excluded from the study. Results: The preintervention cohort consisted of 150 unique PWE, and the postintervention cohort included 379 unique adult PWE and 515 total encounters. Overall percentages of review/adherence of EQMs were significantly improved between the preintervention and postintervention group for counseling for women of childbearing potential (91.7%), intractable epilepsy referral to a comprehensive epilepsy center (74%), quality of life assessment (80%), improvement of quality of life measurements (41.7%), and depression and anxiety screening (85.6%), demonstrating a significant increase when compared with the preintervention group (p < 0.00001). Discussion: A web-based point-of-care EQM application demonstrated significant improvement of the HCP's ability to perform and review EQMs at the point-of-care patient visit. Furthermore, the application was successful in creating opportunities for direct intervention based on the EQMs and chances for better patient education and provider-patient communication. Further considerations would include automated survey requests and expansion into other AAN QMs.

Rasch analysis of fatigue severity scale in patients with epilepsy.

OBJECTIVE: To utilize the Rasch model to validate and assess the psychometric properties of the Fatigue Severity Scale (FSS) in patients with epilepsy. METHODS: A total of 307 patients (age > 18 years) with a confirmed diagnosis of epilepsy were consented to participate. Exclusion criteria included patients with psychogenic nonepileptic events, cognitive disabilities, and patients who did not speak/understand English. The nine-step FSS was programmed into software administered to patients on electronic tablets, and patient responses were auto-scored. The Rasch rating scale model (RSM) was used to evaluate the unidimensionality, reliability, and targeting of the FSS. To assess unidimensionality, we examined infit and outfit mean squares. We also assessed unidimensionality of the FSS using a principal component analysis of Rasch residuals, where residuals are understood as the difference between observed and expected data values. We evaluated the internal consistency of person and item performance by examining separation reliability estimates and separation ratio. Differential Item Functioning (DIF) was calculated for gender. RESULTS: There was mixed evidence regarding the extent to which the FSS fit the Rasch model. Outfit values ranged from 0.52 to 2.72 and infit values were 0.60 to 2.18, strongly suggesting the presence of misfitting items: Item 1 ("My motivation is lower when I am fatigued") and Item 2 ("Exercise brings on my fatigue"). SIGNIFICANCE: The nine-item FSS showed fair psychometric properties in this sample of patients with epilepsy. Our study provides unique, supportive information for the use of a modified version of the FSS, omitting the first two items, in patients with epilepsy. Given the prevalence of fatigue and other neuropsychiatric comorbidities of epilepsy, having a validated fatigue scale can aid healthcare providers to identify moderate-to-severe fatigue levels in patients with epilepsy and address the plausible risk factors.

Did the COVID-19 pandemic impact help-seeking behavior for seizure management? A Google Trends™ study.

Google Trends™ is a popular tool for analyzing healthcare-seeking patterns based on observed changes in the relative search volume (RSV) of the queries made on the Google™ search engine. Google Trends™ was increasingly utilized during the pandemic to assess the impact on mental health, risk communication, the impact of media coverage, and preparedness prediction. The objective of this study was to evaluate the impact of the Coronavirus disease 2019 (COVID-19) pandemic on help-seeking behaviors for seizures and/or epilepsy by assessing the changes in seizure-related online queries in periods before and since the advent of the COVID-19 pandemic on Google Trends™. We compared the RSV volumes in the year prior to and during the COVID-19 pandemic against weekly COVID-19 positive cases for each state and US census regions Search terms were categorized according to seizure symptoms or seizure treatment. Our study showed no significant increase in the RSV for seizure and epilepsy-related searches during the COVID-19 pandemic via Google Trends™. Public health entities and medical systems may use Google Trends ™ as a way to predict national, regional, and local patient needs and drive resources to meet patient demands.

Lacosamide serum concentrations during pregnancy.

Still considered a new ASD, teratogenicity from lacosamide (LCM) exposure during pregnancy is unknown. LCM metabolism through several cytochrome P450 enzymes and minor glucuronidation metabolism in the liver may increase during pregnancy and theoretically lead to lower LCM levels during pregnancy and the risk of increased seizures. Our objective was to determine the impact of pregnancy on serum LCM levels in a series of women with epilepsy (WWE). We identified seven pregnancies with exposure to LCM with at least one level drawn during pregnancy. Patient ages ranged from 18 to 38 years (mean 26.4 years) and total daily doses of LCM ranged from 200 to 600 mg/day. Two patients had increased dose adjustments in response to breakthrough seizures. Dose normalized concentrations (DNC) showed an overall decrease over time through each trimester (p = 0.002) and significantly lower during trimester 2 and 3 (p = 0.001 and p = 0.004, respectively) compared to pre-pregnancy levels. There were no significant changes in seizure frequency and none of the neonates had teratogenic findings at time of birth. We are the first to report a case series on the changes in LCM levels during pregnancy with significant decreased LCM DNC levels during the second and third trimesters in comparison to pre-pregnancy values.

Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a myriad of neurological manifestations and its effects on the nervous system are increasingly recognized. Seizures and status epilepticus (SE) are reported in the novel coronavirus disease (COVID-19), both new onset and worsening of existing epilepsy; however, the exact prevalence is still unknown. The primary aim of this study was to correlate the presence of seizures, status epilepticus, and specific critical care EEG patterns with patient functional outcomes in those with COVID-19. METHODS: This is a retrospective, multicenter cohort of COVID-19-positive patients in Southeast Michigan who underwent electroencephalography (EEG) from March 12th through May 15th, 2020. All patients had confirmed nasopharyngeal PCR for COVID-19. EEG patterns were characterized per 2012 ACNS critical care EEG terminology. Clinical and demographic variables were collected by medical chart review. Outcomes were divided into recovered, recovered with disability, or deceased. RESULTS: Out of the total of 4100 patients hospitalized with COVID-19, 110 patients (2.68%) had EEG during their hospitalization; 64% were male, 67% were African American with mean age of 63 years (range 20-87). The majority (70%) had severe COVID-19, were intubated, or had multi-organ failure. The median length of hospitalization was 26.5 days (IQR = 15 to 44 days). During hospitalization, of the patients who had EEG, 21.8% had new-onset seizure including 7% with status epilepticus, majority (87.5%) with no prior epilepsy. Forty-nine (45%) patients died in the hospital, 46 (42%) recovered but maintained a disability and 15 (14%) recovered without a disability. The EEG findings associated with outcomes were background slowing/attenuation (recovered 60% vs recovered/disabled 96% vs died 96%, p < 0.001) and normal (recovered 27% vs recovered/disabled 0% vs died 1%, p < 0.001). However, these findings were no longer significant after adjusting for severity of COVID-19. CONCLUSION: In this large multicenter study from Southeast Michigan, one of the early COVID-19 epicenters in the US, none of the EEG findings were significantly correlated with outcomes in critically ill COVID-19 patients. Although seizures and status epilepticus could be encountered in COVID-19, the occurrence did not correlate with the patients' functional outcome.

Pregnant patient with extranodal CNS Rosai-Dorfman disease with new-onset seizures: the conundrum of differentiating disease progression from eclampsia.

A 31-year-old woman at 30 weeks gestation presented to the emergency department following multiple seizures. Her history was significant for extranodal Rosai-Dorfman Disease (RDD) with central nervous system (CNS) lesions. RDD, a rare form of non-Langerhans cell histiocytosis, commonly presents with non-tender cervical lymphadenopathy. CNS involvement accounts for a small number of cases in those with extranodal disease. Patients with CNS RDD can have a variety of neurological symptoms, including seizures. Eclampsia, a relatively rare obstetric hypertensive disorder, is always within the differential diagnosis for patients presenting with late gestation seizures. We present the challenging evaluation and treatment of a patient whose clinical picture did not clearly differentiate eclampsia from new onset seizures related to progression of her RDD. This conundrum perhaps resulted in unnecessary preterm operative delivery of a critically ill patient. Only follow-up of the patient helped clarify the likely antepartum diagnosis.

Racial variations in lacosamide serum concentrations in adult patients with epilepsy.

Lacosamide (LCM) is a third-generation anti-epileptic drug (AED) for partial-onset epilepsy with minimal hepatic metabolism and drug-drug interactions. The impact of individual patient variables such as race on drug metabolism have been under-reported in AEDs and LCM has not been specifically investigated. Our aim was to assess the role race plays on serum LCM levels in the management of epilepsy. Thus, we retrospectively reviewed patients with focal seizures who received LCM and had LCM levels as part of their routine clinical care in our Level IV Epilepsy Center. Variables including age, race, gender, LCM serum levels, LCM daily dose, and concomitant AEDs were collected and analyzed. A total of 93 patients with 1-3 clinic visits yielded 122 LCM serum levels. African Americans (AA) comprised 62.3% of our serum samples. Daily LCM doses averaged 350 mg/day (range 50-1000 mg/day). Eighty-nine percent of patients took 1-2 other AEDs. Overall, AA patients had lower LCM levels (mean 6.8 µg/mL) compared to White patients (mean of 7.1 µg/mL) (p = .017) even when considering for the daily dose effect (p = .007). Analysis of co-variables did not have significant effect on LCM levels. Overall, AA patients had a weaker relationship between LCM daily dose (adjusted for weight) and serum levels as compared to White patients and require a higher LCM dose per weight to achieve similar levels. Differences in pharmacogenetics may play an important role in these findings and focus on how these variations impact seizure burden.

Electroencephalogram Characteristics in Critical Ill Patients Before Cardiac Arrest: A Case Series.

Background/Objectives. To illustrate characteristic electroencephalogram (EEG) features in patients prior to their first cardiac arrest. Methods. We identified 15 patients who suffered cardiac arrest during continuous EEG at our institution from June 2016 to June 2019. Eight patients were excluded due to co-administration of intravenous anesthetics (which may confound EEG) or if they had a previous prolonged cardiac arrest (>5 minutes) during the same hospitalization. We collected background information, analyzed the time span and vital signs between the initial background change and cardiac arrest. Results. The time span range (minutes) from initial background change to cardiac arrest was 4 to 483 (average 128.9), initial background change to suppression was 0 to 372 (average 75.6), suppression to cardiac arrest was 1 to 140 (average 53.3), suppression to complete suppression was 0 to 66 (average 20.4), and complete suppression to cardiac arrest was 1 to 111 (average 32.9). Three patients showed background changes more than 160 minutes before cardiac arrest. All patients showed progressive heart rate (HR) decline at or before the beginning of suppression on EEG. HR (beats/min) (mean ± SE) at background change, background suppression, complete suppression, and cardiac arrest was 86.3 ± 7.5, 63.9± 7.5, 36.0 ± 6.8, and 0, respectively. We found statistically significant HR changes (P < .05) between background change and complete suppression time points. Conclusions. Our data indicate that EEG pattern change can occur minutes to hours before the initial cardiac arrest. These patterns may be due to progressive cerebral ischemia. Further studies with broad-scale monitoring of vital signs and evoked potentials may help develop models for predicting cardiac insufficiency.

Effects of Marijuana on Ictal and Interictal EEG Activities in Idiopathic Generalized Epilepsy.

Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series, and clinical trials. However, literature on their EEG effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy treated with cannabis. We blindly reviewed 3 long-term EEGs-a 24-hour study while only on antiepileptic drugs, a 72-hour EEG with Cannabis indica smoked on days 1 and 3 in addition to antiepileptic drugs, and a 48-hour EEG with combination C indica/sativa smoked on day 1 plus antiepileptic drugs. Generalized spike-wave discharges and diffuse paroxysmal fast activity were categorized as interictal and ictal, based on duration of less than 10 seconds or greater, respectively. Data from three studies concatenated into contiguous time series, with usage of marijuana modeled as time-dependent discrete variable while interictal and ictal events constituted dependent variables. Analysis of variance as initial test for significance followed by time series analysis using Generalized Autoregressive Conditional Heteroscedasticity model was performed. Statistical significance for lower interictal events (analysis of variance P = 0.001) was seen during C indica use, but not for C indica/sativa mixture (P = 0.629) or ictal events (P = 0.087). However, time series analysis revealed a significant inverse correlation between marijuana use, with interictal (P < 0.0004) and ictal (P = 0.002) event rates. Using a novel approach to EEG data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use. Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing, are needed to validate our findings.