Summary: Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta‐propeller protein‐associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility‐weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences.

Tenecteplase is replacing alteplase as the fibrinolytic agent of choice for the acute management of ischemic stroke in many adult stroke centers due to practical and pharmacokinetic advantages in the setting of similar outcomes. Although thrombolytic use is increasing for acute childhood stroke, there is very limited experience with tenecteplase in children for any indication, and importantly, there are no data on safety, dosing, or efficacy of tenecteplase for childhood stroke. Changes in fibrinolytic capacity over childhood, pediatric pharmacological considerations such as age-specific differences in drug clearance and volume of distribution, and practical aspects of drug delivery such as availability in children’s hospitals may impact decisions about transitioning from alteplase to tenecteplase for acute pediatric stroke treatment. Pediatric and adult neurologists should prepare institution-specific guidelines and organize prospective data collection.

Predictive modeling is foundational to treatment and long-term management of children with traumatic brain injury (TBI). Assessment of injury severity in the acute-care setting enables early stratification of patients based on their risk of death, lifelong disability, or unfavorable outcome. This review evaluates predictive models that have been developed or validated for pediatric TBI patients. The predictive accuracy of these models, the outcomes and time points predicted, and the variables and statistical methods utilized in model development were compared. Embase, Scopus, MEDLINE ^® , and Web of Science were searched for studies that developed statistical models for predicting patient outcomes following pediatric TBI. Studies were excluded if they focused on adults or non-traumatic brain injury, or if they did not assess classification accuracy. A total of 4538 entries were identified and screened, with 7 studies included for analysis. This included five studies in which adult predictive models were validated for use in the pediatric setting, and two in which new models were derived from a pediatric cohort. Trials of adult prediction tools in pediatric cohorts, including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticoid Randomisation After Significant Head Injury (CRASH)-TBI models, showed comparable accuracy between classification of adults and children. Models derived from pediatric cohorts showed improved accuracy. Most studies solely focused on clinical variables, with two studies incorporating biochemical and imaging variables. Predictive models for pediatric TBI are primarily based on methods and variables identified in adult studies. Although adult models have proven effective in select pediatric cohorts, they may be suboptimal when compared with models derived or adjusted for children.