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.

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.

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.

Mirth and laughter elicited during brain stimulation.

There are few reports of laughter and/or mirth evoked by electrical stimulation of the brain. In this study, we present a patient with intractable epilepsy in whom mirth and laughter was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.