Importance:Seizure-induced brain injury is central to the treatment urgency of new-onset refractory status epilepticus (NORSE). Identifying biomarkers that reflect ongoing neuronal damage could inform therapeutic timing and improve outcomes. Objective:To quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy. Design, Setting, and Participants:This was an international cross-sectional study conducted between 2013 and 2025. Patients were enrolled at 36 hospitals in the US, 2 in Canada, and 1 in Italy, France, and Belgium. Patients with cNORSE and eSE for which biological samples were obtained during ongoing seizure activity were enrolled in the study. Comparison groups without status epilepticus comprised individuals with chronic epilepsy and healthy participants. None were excluded. Exposures:Neurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF). Main Outcomes and Measures:Degree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes. Results:A total of 78 patients with cNORSE (mean [95% CI] age, 37 [30-41] years; 44 female [56%]) and 2 independent cohorts of 211 patients (mean [95% CI] age, 69 [66-71] years; 128 female [61%]) and 73 patients (mean [95% CI] age, 56 [45-65] years; 39 male [53%]) with eSE were included. NfL concentrations were markedly elevated in cNORSE-approximately 10-fold higher in CSF and 4-fold higher in serum-compared with the eSE cohorts (CSF: median [IQR], 6408 [1503-22 963] pg/mL compared with 694 [219-2389] pg/mL; serum: median [IQR], 231 [99-855] pg/mL compared with 55 [20-135] pg/mL; P <.001). Serum NfL levels were nearly 20-fold higher in cNORSE than in the cohort with epilepsy and in healthy controls (median [IQR], 11 [7-19 ] and 7 [5-14 ] pg/mL, respectively). Serum and CSF NfL levels were strongly correlated (Spearman ρ = 0.75; P < .001) and rose sharply between week 1 (median [IQR], 101 [51-137] pg/mL), week 2 (median [IQR], 197 [117-324] pg/mL), and week 3 (median [IQR], 598 [163-1000] pg/mL) after onset (P < .001). In contrast, S100B concentrations did not differ between groups and showed no consistent temporal pattern. NfL discriminated cNORSE from eSE (area under the receiver operating characteristic curve [AUROC], 0.79; 95% CI, 0.68-0.90) and from cohorts without status epilepticus (AUROC, 0.99; 95% CI, 0.78-1.00). Higher serum NfL was independently associated with poor functional outcome at discharge (Glasgow Outcome Scale extended score, 1-4; odds ratio, 1.01; 95% CI, 1.00-1.03; P = .03). Conclusions and Relevance:Results of this cross-sectional study suggest that acute neuroaxonal injury, as reflected by elevated NfL levels, was substantially greater in cNORSE than in the cohorts with eSE and in controls without status epilepticus. The rapid early rise in NfL highlights a narrow therapeutic window, emphasizing the need for prompt, effective, and potentially neuroprotective interventions in cNORSE.

AIM:To clarify the extent to which medical comorbidities and goals-of-care decisions influence death among individuals with childhood-onset hydrocephalus.METHOD:This was a retrospective cohort study of 1705 individuals (759 males, 946 females, mean age 11y 5mo, SD 6y 6mo, range 0-37y 7mo at last follow-up) with childhood-onset hydrocephalus, of whom 88 (5.2%) were deceased. Existing medical records, death records, and publicly available internet sources were analyzed. We estimated hazard ratios for putative risk factors through Cox regression based upon 10 529 person-years of data and quantitatively and qualitatively analyzed the circumstances surrounding each death.RESULTS:Mortality did not differ statistically by demographic factors, although higher proportions of non-White and Hispanic individuals were deceased. Most deaths were related to medical comorbidities rather than hydrocephalus itself. Of the 14 deaths directly related to hydrocephalus, seven were caused by shunt complications and four occurred after decisions to forgo treatment, apparently in response to poor outcomes predicted by the medical team. Half the deaths were preceded by shifts to comfort-based care; however, these decisions appeared to substantially change the patient's clinical trajectory only half the time.INTERPRETATION:Children are more likely to die with, rather than from, hydrocephalus. Our results emphasize the complexities of medical decision-making and the influence of clinicians in guiding these choices.

The coronavirus disease 2019 (COVID-19) pandemic has affected mortality and morbidity across all ages, including children. It is now known that neurological manifestations of COVID-19, ranging from headaches to stroke, may involve the central and/or peripheral nervous system at any age. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with the causative virus of COVID-19, severe acute respiratory syndrome coronavirus 2. Knowledge about mechanisms of neurologic disease is scarce but rapidly growing. COVID-19 neurologic manifestations may have particularly adverse impacts on the developing brain. Emerging data suggest a cohort of patients with COVID-19 will have longitudinal illness affecting their cognitive, physical, and emotional health, but little is known about the long-term impact on affected children and their families. Pediatric collaboratives have begun to provide important initial information on neuroimaging manifestations and the incidence of ischemic stroke in children with COVID 19. The Global Consortium Study of Neurologic Dysfunction in COVID-19-Pediatrics, a multinational collaborative, is working to improve understanding of the epidemiology, mechanisms of neurological manifestations, and the long-term implications of COVID-19 in children and their families.

PurposeRescue medications for status epilepticus (SE) have a relatively high rate of failure. The purpose of this review is to summarize the evidence for the efficacy of novel drugs and early polypharmacotherapy for SE.MethodLiterature review.ResultsNew drugs and treatment strategies aim to target the pathophysiology of SE in order to improve seizure control and outcomes. Changes at the synapse level during SE include a progressive decrease in synaptic GABAA receptors and increase in synaptic NMDA receptors. These changes tend to promote self-sustaining seizures. Current SE guidelines recommend a rapid stepwise treatment using benzodiazepines in monotherapy as the first-line treatment, targeting GABAA synaptic receptors. Novel treatment approaches target GABAA synaptic and extrasynaptic receptors with allopregnanolone, and NMDA receptors with ketamine. Novel rescue treatments used for SE include topiramate, brivaracetam, and perampanel, which are already marketed in epilepsy. Some available drugs not marketed for use in epilepsy have been used in the treatment of SE, and other agents are being studied for this purpose. Early polytherapy, most frequently combining a benzodiazepine with a second-line drug or an NMDA receptor antagonist, might potentially increase seizure control with relatively minor increase in side effects. Although many preclinical studies support novel drugs and early polytherapy in SE, human studies are scarce and inconclusive. Currently, evidence is lacking to recommend specific combinations of these new agents.ConclusionsNovel drugs and strategies target the underlying pathophysiology of SE with the intent to improve seizure control and outcomes.