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.

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.

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.

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.

Frontal lobe hypometabolism associated with Sudden Unexpected Death in Epilepsy (SUDEP) risk: An objective PET study.

OBJECTIVE: Abnormalities of brain structures and neuronal networks have been identified in MRI studies of patients with Sudden Unexpected Death in Epilepsy (SUDEP) as well as in those at elevated risk. The goal of this study was to identify common patterns of objectively detected brain glucose metabolic abnormalities associated with SUDEP patients and those at high SUDEP risk. METHODS: Patients with refractory epilepsy (n = 78, age: 16-61 years, 44 females), who underwent comprehensive presurgical evaluation, were assessed for their risk of SUDEP using the revised SUDEP-7 inventory. From the 57 patients with low SUDEP risk, 35 were selected to match their demographic and clinical characteristics to those with high SUDEP risk (n = 21). [18F]fluoro-deoxy-glucose positron emission tomography (FDG-PET) abnormalities were evaluated in the high- and low-SUDEP risk subgroups compared to FDG-PET scans of a healthy adult control group using statistical parametric mapping (SPM). Individual FDG-PET scans of 4 additional patients, who died from SUDEP, were also analyzed by SPM. RESULTS: Mean SUDEP-7 score was 6.1 in the high and 2.7 in the low SUDEP risk group. MRI showed no lesion in 36 patients (64%). Statistical parametric mapping analysis of the high SUDEP risk subgroup showed bilateral medial frontal and inferior frontal hypometabolism as a common pattern. The low-risk group showed no specific common metabolic abnormalities on SPM group analysis. Individual PET scans of all 4 patients who died from SUDEP also showed bilateral frontal lobe hypometabolism. CONCLUSIONS: These data show that bilateral frontal lobe involvement on FDG-PET, especially the medial and inferior frontal cortex, may be a common metabolic pattern associated with high SUDEP risk and SUDEP itself, in patients with refractory focal epilepsy.

Racial and ethnic trends in antiseizure medications trial enrolment: A systematic review using ClinicalTrials.gov.

OBJECTIVE: To describe the racial and gender distribution in antiseizure medications (ASM) clinical trials using a systemic review of clinical trial registry database. METHODS: We searched ClinicalTrials.gov database for ASM trials registered from September 1988 to January 2019. All randomized and non-randomized trials investigating ASM for epilepsy were included. Trials with intervention other than ASM or condition other than epilepsy were excluded. Data on age, race, ethnicity, and gender were extracted directly from database and from published data where available. Study location, trial identifier, year of completion, and funding sources were also collected. Meta-analysis of proportions was conducted using R software. RESULT: Two hundred and thirty studies conducted globally with 39,576 participants were included. Overall, there are 53 % male on all registered ASM studies globally. For trials conducted in the United States (61 studies/5126 participants), 52 % of the participants were male with the following weighted racial distribution (80 % White 13 % Black 3% Asian 7% Hispanic). Subgroup analysis revealed that non-pharma-sponsored studies (50 studies, 4296 participants) have a higher representation of minorities as compared to pharma-sponsored studies (180 studies, 35,280 participants), including Hispanic (9% vs 3% respectively) and Black (18 % vs 11 % respectively). Temporal trends in racial distribution were noted when the duration of 2007-2019 was split into two groups: 2007-2013 (0% Asian, 5% Hispanic, 20 % Black); 2014-2019 (4% Asian, 7% Hispanic, 8% Black). CONCLUSION: In this systematic review, participation of racial and ethnic minorities of Asian and Hispanic background was under-represented. Disparities of all minorities including Black participants was more notable over time and in studies sponsored by industry. Generalizability of ASM clinical trials to certain subgroups should be further examined.

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.

Seizure-related injury and postictal aggression in refractory epilepsy patients.

OBJECTIVE: In the general population, injury related to seizures often involves falls, head trauma, soft tissue injuries, burns and fractures. Additionally, postictal deleterious behavior changes can by experienced by patients. We seek to identify the risk for seizure-related injury (SRI) and postictal aggression (PIA) in patients with refractory epilepsy. METHODS: Self-reported SRI and PIA were gathered through a seizure questionnaire as part of the epilepsy center's seizure safety protocol. Retrospective review of questionnaire, clinical course, and demographic data was completed. Statistical analysis of variables of interest was done using nonparametric methods. RESULTS: 126 patient questionnaires were completed over a one-year duration. Most patients reported seizure related injury (56.3 %) and postictal aggression (52.4 %). Increased disease duration was associated with seizure related injury and its severity (Kwallis p = 0.025), with number of antiepileptic drugs (AEDs) as significant factors (p = 0.012). Postictal aggression was also associated with a longer duration of epilepsy (Ranksum p = 0.037, t-test p = 0.04) and higher seizure frequency (p = 0.017). Patients who reported seizure related injury and postictal aggression were on more AEDs (p = 0.0003, p = 0.01, respectively), with first-generation AEDs being most contributory. CONCLUSION: The majority of patients with seizures report seizure-related injuries and postictal aggression. Duration and AED regimen are significant risk factors and screening practices can potentially guide safety measures and recommendations.

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.

Updates in Refractory Status Epilepticus.

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status.

Acute Resective Surgery for the Treatment of Refractory Status Epilepticus.

BACKGROUND: To identify the role of acute surgical intervention in the treatment of refractory status epilepticus (RSE). METHODS: Retrospective review of consecutive patients who underwent epilepsy surgery from 2006 to 2015 was done to identify cases where acute surgical intervention was employed for the treatment of RSE. In addition, the adult and pediatric RSE literature was reviewed for reports of surgical treatment of RSE. RESULTS: Nine patients, aged 20-68 years, with various etiologies were identified to have undergone acute surgical resection for the treatment of RSE, aided by electrocorticography. Patients required aggressive medical therapy with antiepileptic drugs and intravenous anesthetic drugs for 10-54 days and underwent extensive neurodiagnostic testing prior to resective surgery. Eight out of nine patients survived and five patients were seizure-free at the last follow-up. The literature revealed 13 adult and 48 pediatric cases where adequate historical detail was available for review and comparison. CONCLUSIONS: We present the largest cohort of consecutive adult patients who underwent resective surgery in the setting of RSE. We also reveal that surgery can be efficacious in aborting status and in some can lead to long-term seizure freedom. Acute surgical intervention is a viable option in prolonged RSE and proper evaluation for such intervention should be conducted, although the timing and type of surgical intervention remain poorly defined.

Characteristics of EEG Interpreters Associated With Higher Interrater Agreement.

PURPOSE: The goal of the project is to determine characteristics of academic neurophysiologist EEG interpreters (EEGers), which predict good interrater agreement (IRA) and to determine the number of EEGers needed to develop an ideal standardized testing and training data set for epileptiform transient (ET) detection algorithms. METHODS: A three-phase scoring method was used. In phase 1, 19 EEGers marked the location of ETs in two hundred 30-second segments of EEG from 200 different patients. In phase 2, EEG events marked by at least 2 EEGers were annotated by 18 EEGers on a 5-point scale to indicate whether they were ETs. In phase 3, a third opinion was obtained from EEGers on any inconsistencies between phase 1 and phase 2 scoring. RESULTS: The IRA for the 18 EEGers was only fair. A select group of the EEGers had good IRA and the other EEGers had low IRA. Board certification by the American Board of Clinical Neurophysiology was associated with better IRA performance but other board certifications, years of fellowship training, and years of practice were not. As the number of EEGers used for scoring is increased, the amount of change in the consensus opinion decreases steadily and is quite low as the group size approaches 10. CONCLUSIONS: The IRA among EEGers varies considerably. The EEGers must be tested before use as scorers for ET annotation research projects. The American Board of Clinical Neurophysiology certification is associated with improved performance. The optimal size for a group of experts scoring ETs in EEG is probably in the 6 to 10 range.

A retrospective cross-sectional study of the prevalence of generalized convulsive status epilepticus in traumatic brain injury: United States 2002-2010.

PURPOSE: To determine the incidence, predictors, and outcomes of generalized convulsive status epilepticus (GCSE) in traumatic brain injury (TBI) patients. METHODS: We conducted a retrospective cross-sectional study of adult patients with acute TBI using the 2002-2010 Nationwide Inpatient Sample (NIS) database of USA. We used multivariable logistic regression analyses to identify independent predictors of GCSE in patients with TBI and to determine the impact of GCSE on outcomes (in-hospital mortality, length of stay, total hospital charges, and discharge disposition). RESULTS: Among 1,457,869 patients hospitalized with TBI, 2315 (0.16%) had GCSE. In-hospital mortality was significantly higher in patients with GCSE (32.5% vs. 9.6%; unadjusted OR 4.54, 95% CI 4.16-4.96; p<0.001; adjusted OR 3.41; 95% CI 3.09-3.76 p<0.001). Patients with GCSE had longer length of stay (17.3 ± 21.9 vs. 6.8 ± 11.1 days; p<0.001), higher total hospital charges ($147,415 ± 162,319 vs. $54,041 ± 90,524; p<0.001), and were less likely to be discharged home (19.8% vs. 52.7%; p<0.001). Using multivariable logistic regression analysis, age >35 years (OR 2.15; 95% CI 1.87-2.47), CNS infections (OR 4.86; 95% CI 3.70-6.38), anoxic brain injury (OR 9.54; 95% CI 8.10-11.22), and acute ischemic stroke (OR 4.09; 95% CI 3.41-4.87) were independent predictors of GCSE in TBI patients. Epilepsy was an independent negative predictor of GCSE (OR 0.74; 95% CI 0.55-0.99). CONCLUSION: Despite its low incidence, GCSE in TBI patients was associated with worse outcomes with threefold higher in-hospital mortality, prolonged hospitalization, higher hospital charges, and worse discharge disposition. Surprisingly, epilepsy is a negative predictor of GCSE in this population.

Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid.

OBJECTIVE: The site of action for antiepileptic drugs (AEDs) is within the brain; however, cerebrospinal fluid (CSF) concentration is highly variable. Lacosamide (LCM) is approved by the U.S. Food and Drug Administration (FDA) for treatment of partial-onset seizures in adults, and has linear pharmacokinetics in serum. Penetration across the blood-brain barrier (BBB) is unknown. This study aims to provide additional insights into the pharmacokinetics of LCM. METHODS: Thirty adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor were recruited and were either taking LCM long term (group 1, n = 15), or were LCM naive, receiving LCM as prophylaxis for surgery (group 2, n = 15). All patients received one intravenous (IV) dose (15 min infusion) immediately prior to craniotomy. CSF and arterial blood were collected simultaneously following craniotomy. LCM concentrations were measured in serum and CSF. RESULTS: LCM concentration differences between groups 1 and 2 for both CSF and serum were statistically significant (p ≤ 0.0005), but there was no statistically significant difference in CSF/serum ratios (group 1 = 0.726 ± 0.231; group 2 = 0.556 ±0.241; p = 0.0585). LCM concentration in serum correlated positively with CSF concentration in group 1 (Pearson r = 0.8527, p < 0.0001). The time interval between the end of dose delivery and sample collection correlated positively with the CSF/serum ratio for the drug-naive group (Pearson r = 0.6525; p = 0.0084). Treatment with other AEDs did not affect LCM distribution between serum and CSF. SIGNIFICANCE: Although chronic dosing resulted in higher LCM concentrations in serum and CSF compared to drug-naive patients, the CSF/serum ratio was not affected by LCM pretreatment. These data suggest that LCM serum concentration may reliably predict CSF concentration.

Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus.

Refractory status epilepticus (RSE) can lack overt clinical manifestation and is usually treated with continuous infusion of intravenous anesthetic drugs (IVADs), where the use of continuous electroencephalography (cEEG) is imperative. Ketamine has recently been shown to be effective in the treatment of RSE. We retrospectively review a cohort of 11 patients receiving ketamine as part of their treatment regimen for RSE. We report on the presence of a characteristic EEG rhythm consisting of a generalized archiform theta to beta rhythms (7-20 Hz) appearing after ketamine administration. This pattern was seen in five patients, four of whom achieved successful resolution of RSE. Ketamine-induced EEG pattern may serve as a biomarker predictive of successful treatment outcome in RSE.