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Purpose To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. Method We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. Results We analyzed 368 patients (58% males) with a median (p25 – p75) age of 4.2 (1.3–9.7) years. The MESOR was 15.3 (95% CI: 13.9–16.8) and the amplitude was 3.2 (95% CI: 1.1–5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am–12 pm) and trough at night (11 pm–12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am–3 am) with a minimum during the afternoon (2 pm–3 pm) (p = 0.0179). Conclusions The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am–12 pm) and a trough at night (11 pm-12am).

Purpose To summarize the available evidence related to pediatric refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE), with emphasis on epidemiology, etiologies, therapeutic approaches, and clinical outcomes. Methods Narrative review of the medical literature using MEDLINE database. Results RSE is defined as status epilepticus (SE) that fails to respond to adequately used first- and second-line antiepileptic drugs. SRSE occurs when SE persist for 24 h or more after administration of anesthesia, or recurs after its withdrawal. RSE and SRSE represent complex neurological emergencies associated with long-term neurological dysfunction and high mortality. Challenges in management arise as the underlying etiology is not always promptly recognized and therapeutic options become limited with prolonged seizures. Treatment decisions mainly rely on case series or experts’ opinions. The comparative effectiveness of different treatment strategies has not been evaluated in large prospective series or randomized clinical trials. Continuous infusion of anesthetic agents is the most common treatment for RSE and SRSE, although many questions on optimal dosing and rate of administration remain unanswered. The use of non-pharmacological therapies is documented in case series or reports with low level of evidence. In addition to neurological complications resulting from prolonged seizures, children with RSE/SRSE often develop systemic complications associated with polypharmacy and prolonged hospital stay. Conclusion RSE and SRSE are neurological emergencies with limited therapeutic options. Multi-national collaborative efforts are desirable to evaluate the safety and efficacy of current RSE/SRSE therapies, and potentially impact patients’ outcomes.