Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the \u27pediatric Status Epilepticus Research Group\u27 (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE

Prenatal exposure to DDT and pyrethroids for malaria control and child neurodevelopment : the VHEMBE Cohort, South Africa

BACKGROUND : Although indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) and pyrethroids effectively controls malaria, it potentially increases human exposure to these insecticides. Previous studies suggest that prenatal exposure to these insecticides may impact human neurodevelopment.OBJECTIVES : We aimed to estimate the effects of maternal insecticide exposure and neurodevelopment of toddlers living in a malaria-endemic region currently using IRS. METHODS: The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort of 752 mother-child pairs in Limpopo, South Africa. We measured maternal exposure to DDT and its breakdown product, dichlorodiphenyldichloroethylene (DDE), in maternal serum, and measured pyrethroid metabolites in maternal urine. We assessed children's neurodevelopment at 1 and 2 y of age using the Bayley Scales of Infant Development, third edition (BSID-III), and examined associations with maternal exposure. RESULTS : DDT and DDE were not associated with significantly lower scores for any BSID-III scale. In contrast, each 10-fold increase in cis-DCCA, trans-DCCA, and 3-phenoxybenzoic acid were associated, respectively, with a -0.63 (95% CI: -1.14, -0.12), -0.48 (95% CI: -0.92, -0.05), and -0.58 (-1.11, -0.06) decrement in Social-Emotional scores at 1 y of age. In addition, each 10-fold increase in maternal cis-DBCA levels was associated with significant decrements at 2 y of age in Language Composite scores and Expressive Communication scores [β=-1.74 (95% CI: -3.34, -0.13) and β=-0.40 (95% CI: -0.77, -0.04), respectively, for a 10-fold increase]. Significant differences by sex were estimated for pyrethroid metabolites and motor function scores at 2 y of age, with higher scores for boys and lower scores for girls. CONCLUSIONS : Prenatal exposure to pyrethroids may be associated at 1 y of age with poorer social-emotional development. At 2 y of age, poorer language development was observed with higher prenatal pyrethroid levels. Considering the widespread use of pyrethroids, these findings deserve further investigation.The National Institutes of Health/National Institute of Environmental Health Sciences, grant 1R01ES020360-01(B.E.) and the Canada Research Chairs program (J.C.).http://ehp.niehs.nih.govam2018School of Health Systems and Public Health (SHSPH)Urolog

Comparison of pediatric patients with status epilepticus lasting 5-29 min versus ≥30 min.

The most common thresholds for considering prolonged seizures as status epilepticus (SE) are 5 and 30 min. It is unknown whether these different thresholds (5 or 30 min) identify patient populations with different electroclinical characteristics. We compared the characteristics of patients with SE lasting 5-29 min (SE5-29) with those with SE lasting ≥30 min (SE≥30). Inclusion criteria were the following: 1) 1 month to 21 years of age at the time of SE, 2) convulsive seizures, and 3) seizure duration ≥5 min. Exclusion criteria were the following: 1) exclusively neonatal seizures, 2) psychogenic nonepileptic seizures, or 3) incomplete information about seizure duration. Four hundred forty-five patients (50.1% male) with a median (p25-p75) age at SE of 5.5 (2.8-10.5) years were enrolled. Status epilepticus lasted for 5-29 min in 296 (66.5%) of subjects and for ≥30 min in 149 (33.5%). Patients with SE≥30 were younger than the patients with SE5-29 at the time of seizure onset (median: 1 versus 2.1 years, p=0.0007). Status epilepticus as the first seizure presentation was more frequent in patients with SE≥30 (24.2% versus 12.2%, p=0.002). There was a tendency towards a higher rate of abnormalities in the magnetic resonance imaging at baseline in patients with SE≥30 (70.5% versus 57.1%, p=0.061). Differences were not detected in seizure frequency, seizure types, presence of developmental delay, and electroencephalogram abnormalities at baseline. In the pediatric population, SE thresholds of either 5 or 30 min identify groups of patients with very similar electroclinical characteristics, which may influence future definitions of pediatric SE