Approximately half of strokes in children are hemorrhagic, but basic epidemiologic factors remain understudied. We sought to create an international, multicenter registry of children who sustained an acute hemorrhagic stroke. Methods: Longitudinal cohort study within the existing infrastructure of the International Pediatric Stroke Study consortium. Inclusion: children < 18 years with spontaneous hemorrhagic stroke (intraparenchymal, intraventricular, subarachnoid or subpial hemorrhage). Exclusion: hemorrhage due to trauma; hemorrhagic transformation of a primary ischemic infarction; isolated subdural or epidural hemorrhage. Clinical data were collected at local sites after ethics approval. Outcomes were measured using the Pediatric Stroke Outcome Measure (PSOM) a 10-point scale where 0-1 indicates good outcome (defined as no/minimal functional deficit). Results: Investigators at 24 sites enrolled 406 patients, which included both neonatal (n=75,18.5%) and childhood strokes (n=331, 81.5%). Demographics and clinical characteristics are shown in Table 1. A neurovascular anomaly was identified as a source of hemorrhage in 9 neonates (12%) and 241 children (72.8%). Death due to stroke occurred in 20 (4.9%), and an additional 7 (1.7%) died from other causes prior to hospital discharge. Table 2 provides survivor outcomes, stratified by age group at the time of stroke. PSOM was available for 60 (86%) of neonatal hemorrhagic stroke survivors at a median of 1.8 months. Among these, 83% had a good outcome (as a continuous measure: median 0, interquartile range 0, 5). After childhood hemorrhagic stroke, a PSOM was available in 237 (76%) at a median of 8.4 months post-stroke, and 73% were categorized as a good outcome (as a continuous measure: median 0.5, interquartile range 0, 1.5). Conclusions: Neurovascular anomalies such as brain arteriovenous malformation, arteriovenous fistula or aneurysm were frequently identified in children with hemorrhagic stroke. These findings maybe an underestimate due to lack of vascular imaging. Chronic hypertension is an infrequent risk factor. Most of the survivors with available follow-up attained good outcomes. Vascular imaging is critical for children with hemorrhagic stroke to identify potentially treatable anomalies and prevent stroke recurrence.

OBJECTIVE:Status epilepticus (SE) treatment is more effective when benzodiazepines (BZDs) are given soon after SE diagnosis. The Quality Improvement in Time to Treat Status Epilepticus (QuITT-SE) trial is a multicenter, randomized, stepped-wedge effectiveness-implementation hybrid study aimed at improving time to SE treatment. We report the QuITT-SE baseline cohort and test the hypothesis that acute seizure emergency episodes treated promptly differ in clinical and demographic features from those with delayed treatment. METHODS:Data were summarized from 371 consecutive acute seizures episodes treated with a BZD in the inpatient, non-intensive care unit (ICU) setting from 207 individual patients across eight centers per the QuITT-SE protocol. To test our hypothesis, we utilized a multivariable negative binomial mixed effects model with random intercepts to estimate the incidence rate ratios for variables of interest for time to BZD treatment. RESULTS:The median age was 7 years (IQR = 3-12). Nonelective ICU transfers occurred with 26% of episodes, including 13% within 6 h of the episode. The median time from seizure onset to BZD treatment was 6 min (IQR = 4-10), with 74% of all episodes and 63% of SE treated within 10 min. BZD administration was faster when nurses made the treatment decision, when the intranasal (IN) route was used, when the patient received prior rescue medication within 24 h, or with certain elective admission types. Seizures were shorter when BZD administration was faster or when treatment was with IN midazolam versus intravenous lorazepam (median = 8 min [IQR = 6-15] vs. 10 min [IQR = 7-17], p = .04). Patients were less likely to be transferred to the ICU if they received IN midazolam (odds ratio = .3, p = .007). SIGNIFICANCE:Delayed BZD administration occurs in one third of SE treatment. Prolonged seizures and ICU transfers are associated with modifiable risk factors. Baseline drivers of delayed acute seizure treatment may be addressed using the QuITT-SE interventions, the study of which is currently ongoing.

Background Cardiac catheterization in children with heart disease is associated with an increased risk of arterial ischemic stroke. We created and evaluated the diagnostic performance of a bedside screening tool administered postprocedure to identify arterial ischemic stroke. Methods We developed a postprocedure stroke screen comprising history of stroke, responsiveness, command following, speech, facial and limb strength symmetry, new seizure, and caregiver concern. We compared the performance of the screening tool in a retrospective cohort of 21 patients with a postcatheterization arterial ischemic stroke and a prospective cohort of 100 consecutive control patients after cardiac catheterization. Results The postprocedure stroke screen delivered a maximum Youden index ranging from 0.810 to 0.937 at threshold scores of 2 or 2.5 and gave a sensitivity and specificity >0.9. The area under the receiver operating characteristic curve ranged from 0.931 to 0.946. Conclusions We developed a screening tool with high sensitivity and specificity to identify postcatheterization arterial ischemic stroke in children.

Introduction: Ischemic stroke in adults demonstrates circadian variation in the timing of onset of symptoms, with the highest risk between 6am and noon (1-4). The influence of circadian timing on stroke biology may differ between children and adults, possibly related to the immature circadian system, variations in school versus work schedules, and diverse stroke pathophysiology (5). The goal of our study was to assess whether timing of ischemic stroke onset demonstrates circadian variability in children. Methods: We queried the International Pediatric Stroke Study, an international multicenter observational registry of children <18 years with arterial ischemic stroke (AIS). Included patients were aged 29 days-18 years with outpatient AIS and known time of stroke symptom onset. Clinical and radiographic features were compared according to 4 distinct time epochs: 6:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening) and 00:00-5:59 (night). Clinical outcomes were defined by the Pediatric Stroke Outcome Measure (PSOM). Baseline, clinical and outcome characteristics were compared between the 4 time epochs using independent samples Kruskal-Wallis and Chi-square tests. Pairwise comparisons were conducted where needed. Results: A total of 478 patients met inclusion criteria, 54% male, mean age 9.9±SD 5.7 years. Time of stroke onset by hour is shown in Figure 1. Most strokes occurred in the afternoon (n=185, 38.7%), followed by morning (n=156, 32.6%). Table 1 shows demographic and clinical characteristics by time epoch; clinical and arteriopathy risk factors were more prevalent in nighttime strokes (23/36, 70%, p=0.034). Median PSOM scores at 6 months appeared to be better after evening strokes (0.5, IQR 0-1.5) as compared to morning strokes (1, IQR 0.5-2) and afternoon strokes (1, IQR 0.5-3, p=0.033), but failed adjustment for multiple comparisons (figure 2). Conclusion: Circadian influence on stroke timing appears to differ between adults and children. Further prospective studies with larger sample sizes are needed to understand the impact of circadian rhythm on stroke in childhood.

OBJECTIVES:To review the timing of extracorporeal life support (ECLS)-related focal cerebral injury (FCI) in relation to circuit interruptions in children and young adults. DESIGN:Retrospective study from January 1, 2015, to December 31, 2023. SETTING:Single-center academic children's hospital. PATIENTS:Children and young adults younger than 21 years old who had neuroimaging during or after ECLS. Multiple ECLS runs in individual patients were analyzed as distinct runs. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:FCI was radiographically defined as lateralized ischemia or hemorrhagic parenchymal brain injury greater than 1 cm 3 or as subdural hemorrhage causing midline shift. Timing of clinical FCI documentation was abstracted from chart review and based on times of new-onset focal neurologic examination findings, focal electroencephalography findings, or incidental discovery on imaging. In instances of FCI, electroencephalography reports and inpatient progress notes were reviewed to identify electroencephalography-related timing of FCI. Institutional ECLS registry data were used to identify times of circuit events (i.e., cannulation, decannulation, and circuit interruptions). The probable time course of FCI after circuit events was evaluated in the ECLS runs with an imaging diagnosis of FCI, and summarized using cumulative distribution with 95% CI. In 101 ECLS runs in 94 patients with brain imaging, 20 had FCI: ischemic stroke in 12, intraparenchymal hemorrhage in six, and subdural hemorrhage with midline shift in two. Eighteen FCIs were documented within 48 hours of a circuit event. Among 13 FCIs with electroencephalography recording at the time of FCIs, eight had new-onset subclinical electroencephalography abnormality as the initial documented sign of FCI. The presence of FCI vs. not was associated with lower survival to decannulation ( p = 0.007). CONCLUSIONS:In this single-center retrospective series, 2015-2023, the majority of ECLS-related FCIs were evident within 48 hours of ECLS cannulation, decannulation, or circuit interruption. These events warrant increased surveillance for neurologic complications.

BACKGROUND:Acute seizures may evolve into status epilepticus (SE), prolonged and self-sustaining seizures that may result in brain injury or death. Rapid treatment with a benzodiazepine (BZD) is most effective. However, SE treatment remains delayed in many cases. We previously performed a single-center quality improvement study which resulted in more rapid treatment, decreased intensive care utilization, and decreased cost. Now, we are conducting a multicenter trial to test the hypothesis that pragmatic changes in treating acute inpatient seizures reduce time and are implementable across diverse hospital settings. METHODS/DESIGN:We designed a multicenter stepped wedge cluster randomized trial with three unidirectional 12-month steps following one baseline step. After dissemination visits, sites will attempt to implement a standardized bundle consisting of: (1) standardize default BZD to non-IV; (2) target treatment time within 10 min; (3) relocate and bundle items for BZD administration to a single location; (4) prioritize basic seizure first aid as initial assessment; (5) implement SE-specific documentation templates; (6) implement multidisciplinary site QI teams. Our primary outcome is median time from seizure diagnosis to BZD administration. Secondary outcomes are median changes in Pediatric Cerebral Performance Category score, ICU transfer rate, and cost of hospitalization. We will study implementation outcomes using mixed methods based on the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. DISCUSSION:QuITT-SE is designed to test the effect and implementation of a pragmatic set of interventions on treatment times in SE. If successful, results will provide a generalizable roadmap for broad implementation through healthcare systems that should improve outcomes in SE. TRIAL REGISTRATION:Clinicaltrials.gov (NCT06194747). Funded by the National Institutes of Health (R01NS133037).

ObjectivesIntravenous tenecteplase (TNK) is increasingly used to treat adult patients with acute arterial ischemic stroke, but the risk profile of TNK in childhood stroke is unknown. This study aims to prospectively gather safety data regarding TNK administration in children.MethodsSince December 2023, a monthly email survey was sent to participants recruited from the International Pediatric Stroke Study and Pediatric Neurocritical Care Research Group querying recent experience with TNK in childhood stroke. Limited demographic, safety, and outcome data were collected in a secure REDCap database. Detailed clinical data were not collected.ResultsEleven children were reported to have received TNK between February 2023 and January 2024. Ten were adolescents (13-17 years old), and 1 was between 5 and 12 years old. TNK was given at an outside facility before transfer to the reporting facility in 7 cases. Final diagnosis was stroke in 8 cases and stroke mimic in 3 cases. No major safety concerns or TNK-related intracranial hemorrhages on follow-up imaging were reported.DiscussionOur initial data suggest that TNK may be safe in childhood arterial ischemic stroke. Strategically designed prospective studies are needed to further define safety, optimal dosage, and efficacy of TNK in acute pediatric stroke.

Autopsy studies of children dying of cerebral malaria (CM) have revealed that those with malarial retinopathy exhibited high levels of sequestration in the cerebral vasculature, whereas children with retinopathy-negative CM exhibited lower sequestration levels and possible nonmalarial causes of death. This suggests that children dying of retinopathy-negative CM have nonmalarial coma etiologies with concomitant incidental parasitemia, which is common in high malaria transmission areas. Subsequent studies have challenged this assertion, positing that retinopathy-negative CM and retinopathy-positive CM are variants of the same disease pathophysiology or host biology, both caused by acute malaria infection. We recently determined that electroencephalography (EEG) can be used to discriminate between a malarial coma (CM) and a nonmalarial coma. To better understand the contribution of acute malaria infection in the pathophysiology of retinopathy-negative CM, we compared qualitative and quantitative EEG findings from 30-minute EEG recordings of Malawian children aged 3 months to 14 years hospitalized at Queen Elizabeth Central Hospital with retinopathy-negative CM, retinopathy-positive CM, and nonmalarial coma. Neither qualitative nor quantitative EEG interpretation methods allow for the discrimination between children with retinopathy-positive CM and those with retinopathy-negative CM. Conversely, quantitative EEG readily differentiated children with retinopathy-negative CM from those with nonmalarial coma (area under the receiving operating characteristic [AUROC] curve of 0.83). When combining qualitative and quantitative EEG interpretation methods, the ability of EEG to distinguish retinopathy-negative CM from nonmalarial EEG increases (AUROC of 0.87). The EEGs of children with retinopathy-negative CM are similar to those of children with retinopathy-positive CM and significantly different from those of children with nonmalarial coma, supporting the hypothesis that acute malarial infection is pathophysiologically important in retinopathy-negative CM.