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AbstractObjectiveThis study was undertaken to describe long‐term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE.MethodsWe performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients.ResultsFollow‐up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow‐up duration was 1.6 (.9–2.7) years. The in‐hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty‐six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1–134.5] h vs. 4 [1.6–16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008–1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale‐Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion.SignificanceAbout one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow‐up, with longer electroclinical RSE duration as a predictor.

OBJECTIVES: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN: Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING: Seventeen academic hospitals in the United States. PATIENTS: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 281 patients (157 males) with a median age of 4.1 years (1.3–9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55–491.5 min] vs 62 min [33.3–120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5–1,255 min] vs 150 min [90–318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58–368 hr] vs 3 hr [1.4–5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5–40 d] vs [1.8–8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

AbstractObjectiveWe aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE).MethodsPatients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever.ResultsOf 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function.SignificanceAmong pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection‐related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

AbstractFebrile‐infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin‐1 receptor antagonist, as an immunomodulator for FIRES. Anakinra was potentially safe with only one child discontinuing therapy due to infection. Earlier anakinra initiation was associated with shorter duration of mechanical ventilation, ICU and hospital length of stay. Our retrospective data lay the groundwork for prospective consensus‐driven cohort studies of anakinra in FIRES.

Purpose: We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies. Methods: We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports. We compared reports generated using free text or templates. Results: We reviewed 191 EEG reports. Agreement between the electroencephalographers regarding whether a variable was described in the report ranged from fair to very good. The presence of electrographic seizures (ES) was documented in 46% (87/191) of reports, and these reports documented the time of first ES in 64% (56/87), ES duration in 72% (63/85), and ES frequency in 68% (59/87). Reactivity was documented in 16% (31/191) of reports, and it was more often documented in template than in free-text reports (40% vs. 14%, P = 0.006). Other variables were not differentially reported in template versus free-text reports. Conclusions: Many key EEG features are not documented consistently in clinical continuous EEG monitoring reports, including ES characteristics and reactivity assessment. Standardization may be needed for clinical EEG reports to provide informative data for large multicenter observational studies.