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.

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.

COVID-19 Continuous-EEG Case Series: A Descriptive Study.

PURPOSE: Corona virus disease 2019 (COVID-19) refers to coronavirus disease secondary to SARS-CoV2 infection mainly affecting the human respiratory system. The SARS-CoV2 has been reported to have neurotropic and neuroinvasive features and neurological sequalae with wide range of reported neurological manifestations, including cerebrovascular disease, skeletal muscle injury, meningitis, encephalitis, and demyelination, as well as seizures and focal status epilepticus. In this case series, we analyzed the continuous video-EEGs of patients with COVID-19 infection to determine the presence of specific EEG features or epileptogenicity. METHODS: All continuous video-EEG tracings done on SARS-CoV2-positive patients during a 2-week period from April 5, 2020, to April 19, 2020, were reviewed. The demographics, clinical characteristics, imaging, and EEG features were analyzed and presented. RESULTS: Of 23 patients undergoing continuous video-EEG, 16 were COVID positive and were included. Continuous video-EEG monitoring was ordered for "altered mental status" in 11 of 16 patients and for "clinical seizure" in 5 of 16 patients. None of the patients had seizures or status epilepticus as a presenting symptom of COVID-19 infection. Instead, witnessed clinical seizures developed as results of COVID-19-related medical illness(es): anoxic brain injury, stroke/hemorrhage, lithium (Li) toxicity (because of kidney failure), hypertension, and renal disease. Three patients required therapeutic burst suppression because of focal nonconvulsive status epilepticus, status epilepticus/myoclonus secondary to anoxic injury from cardiac arrest, and one for sedation (and with concomitant EEG abnormalities secondary to Li toxicity). CONCLUSIONS: In this observational case series of 16 patients with COVID-19 who were monitored with continuous video-EEG, most patients experienced a nonspecific encephalopathy. Clinical seizures and electrographic status epilepticus were the second most commonly observed neurological problem.

Neurological manifestations as primary presentation of COVID-19 in hospitalized patients.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. METHODS: We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. RESULTS: Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. CONCLUSION: Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy.

The vagus nerve stimulation (VNS) Therapy® System is the first FDA-approved medical device therapy for the treatment of drug-resistant epilepsy. Over the past two decades, the technology has evolved through multiple iterations resulting in software-related updates and implantable lead and generator hardware improvements. Healthcare providers today commonly encounter a range of single- and dual-pin generators (models 100, 101, 102, 102R, 103, 104, 105, 106, 1000) and related programming systems (models 250, 3000), all of which have their own subtle, but practical differences. It can therefore be a daunting task to go through the manuals of these implant models for comparison, some of which are not readily available. In this review, we highlight the technological evolution of the VNS Therapy System with respect to device approval milestones and provide a comparison of conventional open-loop vs. the latest closed-loop generator models. Battery longevity projections and an in-depth examination of stimulation mode interactions are also presented to further differentiate amongst generator models.

Prognostic Significance of Cyclic Seizures in Status Epilepticus.

PURPOSE: Status epilepticus (SE) is a commonly encountered neurologic condition associated with high mortality rates. Cyclic seizures (CS) are a common form of SE, but its prognostic significance has not been well established. In this retrospective study, the mortality of cyclic versus noncyclic forms (NCSs) of SE are compared. METHODS: A total of 271 patients were identified as having seizures or SE on EEG reports, of which 65 patients were confirmed as having SE. Based on EEG characteristics, the patients were then classified as cyclic or noncyclic patterns. Cyclic seizures were defined as recurrent seizures occurring at nearly regular and uniform intervals. Noncyclic form included all other patterns of SE. Pertinent clinical data were collected and reviewed for each case. RESULTS: Of the 65 patients with SE, 25 patients had CS and 40 patients had NCS. Patients with CS showed a lower rate of in-hospital mortality although not statistically significant (P = 0.19). When looking at patients younger than 75 years, the CS group had significantly lower in-hospital mortality rate (P = 0.007). CONCLUSIONS: The findings of this study suggest that CS may have a more favorable outcome compared with NCS in patients younger than 75 years. This study is also the first to report the rate of CS among all cases of confirmed SE (38%). Future studies with a larger sample size are needed to further evaluate the difference in outcome between CS and NCS.