Hocker, Sara

AbstractIn 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.

Abstract 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.

ABSTRACTSeizures and other electrophysiological disturbances are an under‐recognized cause of coma, focal deficits, and prolonged encephalopathy following subdural hematoma evacuation. In these patients, it is possible that seizures remain unrecognized on scalp EEG. It has been shown that a high burden of seizures and other electrophysiological disturbances exist following surgical evacuation and underlie the encephalopathy commonly seen in this patient population, predisposing them to medical complications and confounding estimates of prognosis. As part of a research protocol, we are performing intraoperative placement of cortical surface (non‐parenchyma penetrating) intracranial EEG on patients who present after trauma and require emergent decompressive hemicraniectomy.In this case report of a patient with high‐velocity traumatic epidural, subdural, and subarachnoid hemorrhages, we identified frequent non‐convulsive seizures or seizure‐like SIRPIDs with intracranial cortical surface monitoring that were not identified on simultaneous scalp EEG. Stimulation consistently triggered these electrographic seizures in addition to rhythmic lateralized periodic discharges. His mental status improved rapidly after resolution of these electrographic seizures shortly after increasing antiseizure medications, suggesting that they may have been contributing to his encephalopathy. More research is needed to determine the frequency of this phenomenon and determine whether treatment of such seizures improves patient outcomes.

Objectives: To determine the causes of death in patients with status epilepticus. To analyze the relative contributions of seizure etiology, seizure refractoriness, use of mechanical ventilation, anesthetic drugs for seizure control, and medical complications to in-hospital and 90-day mortality, hospital length of stay, and discharge disposition. Design: Retrospective cohort. Setting: Single-center neuroscience ICU. Participants: Patients with status epilepticus were identified by retrospective search of electronic database from January 1, 2011, to December 31, 2016. Interventions: Review of electronic medical records. Measurements and Main Results: Demographics, clinical characteristics, treatments, and outcomes were collected. Univariable and multivariable logistic regression analysis were used to determine whether the use of anesthetic drugs, mechanical ventilation, Status Epilepticus Severity Score, refractoriness of seizures, etiology of seizures, or medical complications were associated with in-hospital, 90-day mortality or discharge disposition. Among 244 patients with status epilepticus (mean age was 64 yr [interquartile range, 42–76], 55% male, median Status Epilepticus Severity Score 3 [interquartile range, 2–4]), 24 received anesthetic drug infusions for seizure control. In-hospital and 90-day mortality rates were 9.2% and 19.2%, respectively. Death was preceded by withdrawal of life-sustaining treatment in 19 patients (86.3%) and cardiac arrest in three (13.7%). Only Status Epilepticus Severity Score was associated with in-hospital and 90-day mortality, whereas the use of anesthetic drugs for seizure control, mechanical ventilation, medical complications, etiology, and refractoriness of seizures were not. Hospital length of stay was longer in patients with medical complications ( p = 0.0091), refractory seizures ( p = 0.0077), and in those who required anesthetic drugs for seizure control ( p = 0.0035). Patients who had refractory seizures were less likely to be discharged home (odds ratio, 0.295; CI, 0.143–0.608; p = 0.0009). Conclusions: In this cohort, death primarily resulted from the underlying neurologic disease and withdrawal of life-sustaining treatment and not from our treatment choices. Use of anesthetic drugs, medical complications, and mechanical ventilation were not associated with in-hospital and 90-day mortality.

SummaryObjectiveIn patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE).MethodsRetrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected.ResultsOne hundred seventy‐seven patients with mean age 63 ± 18 years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow‐up was 3.8 ± 3.2 years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow‐up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P = 0.009) and those with RSE (P = 0.048, odds ratio = 2.12, 95% confidence interval = 1.00‐4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence.SignificanceWe found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

SummaryWorsening pharmacoresistance to antiseizure drugs is common with ongoing excitotoxic neuronal and systemic injury. Early initiation of anesthetic drugs in refractory status epilepticus (RSE) may halt these processes while allowing time for treatment targeting the cause of the seizures. Current guidelines support the use of anesthetic drugs as the third line pharmacologic therapy in generalized convulsive status epilepticus but do not clearly define the indications for these drugs in other types of status epilepticus. There is wide practice variation in choice of third line therapy for RSE, but there is overall consensus that anesthetics should be initiated earlier in generalized convulsive status epilepticus than in nonconvulsive forms. More recently, doubt has been cast on the appropriateness of anesthetic treatment of RSE following a series of studies associating their use with higher mortality and morbidity. This suggests that efforts should focus on determination of who benefits most, optimal use, and prevention of refractoriness. The risk‐benefit ratio of anesthetic use is discussed, with specific indications proposed. In addition, anesthetic dosing, supportive neurocritical care, electroencephalogram suppression target, and weaning of anesthesia are reviewed.