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.

Dual Treatment of Refractory Focal Epilepsy and Obsessive-Compulsive Disorder With Intracranial Responsive Neurostimulation.

Purpose of the Review: Intracranial neurostimulation is a well-established treatment of neurologic conditions such as drug-resistant epilepsy (DRE) and movement disorders, and there is emerging evidence for using deep brain stimulation to treat obsessive-compulsive disorder (OCD) and depression. Nearly all published reports of intracranial neurostimulation have focused on implanting a single device to treat a single condition. The purpose of this review was to educate neurology clinicians on the background literature informing dual treatment of 2 comorbid neuropsychiatric conditions epilepsy and OCD, discuss ethical and logistical challenges to dual neuropsychiatric treatment with a single device, and demonstrate the promise and pitfalls of this approach through discussion of the first-in-human closed-looped responsive neurostimulator (RNS) implanted to treat both DRE (on-label) and OCD (off-label). Recent Findings: We report the first implantation of an intracranial closed-loop neurostimulation device (the RNS system) with the primary goal of treating DRE and a secondary exploratory goal of managing treatment-refractory OCD. The RNS system detects electrophysiologic activity and delivers electrical stimulation through 1 or 2 electrodes implanted into a patient's seizure-onset zones (SOZs). In this case report, we describe a patient with treatment-refractory epilepsy and OCD where the first lead was implanted in the right superior temporal gyrus to target the most active SOZ based on stereotactic EEG (sEEG) recordings and semiology. The second lead was implanted to target the right anterior peri-insular region (a secondary SOZ on sEEG) with the distal-most contacts in the right nucleus accumbens, a putative target for OCD neurostimulation treatment. The RNS system was programmed to detect and record the unique electrophysiologic signature of both the patient's seizures and compulsions and then deliver tailored electrical pulses to disrupt the pathologic circuitry. Summary: Dual treatment of refractory focal epilepsy and OCD with an intracranial closed-loop neurostimulation device is feasible, safe, and potentially effective. However, there are logistical challenges and ethical considerations to this novel approach to treatment, which require complex care coordination by a large multidisciplinary team.

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.

Novel Use of Responsive Neurostimulation (RNS System) in the Treatment of Super Refractory Status Epilepticus.

There are very few randomized controlled trials studying treatment of super refractory status epilepticus (SE), despite estimated occurrence in about 15% of SE cases and its association with high morbidity and mortality rates. Small case series and case reports have described use of neurostimulation, including vagal nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation, to treat super refractory SE when medical interventions have failed. To our knowledge, this is the first reported case of responsive neurostimulation being used to successfully treat a case of super refractory SE. A 37-year-old man with refractory focal epilepsy and a known focal cortical dysplasia involving motor cortex was implanted with an RNS System device after being in super refractory SE for 20 days. Responsive neurostimulation strip and depth electrodes were placed targeting the cortical dysplasia. Detection and stimulation parameters were adjusted over a 14-day period, as medications were gradually weaned. Seizures abated 15 days after implant, 24 hours after stimulation parameters were configured to mimic seizure offset pattern. Seizure remission was sustained, allowing the patient to be weaned off sedating medications and discharged to a rehabilitation facility. At 6 weeks of follow-up, the patient was near his neurologic baseline with no focal deficits.