Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury.

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Background and Purpose— The purposes of this study were to describe features of children with intracerebral hemorrhage (ICH) and to determine predictors of short-term outcome in a single-center prospective cohort study. Methods— A single-center prospective consecutive cohort study was conducted of spontaneous ICH in children aged 1 to 18 years from January 2006 to June 2008. Exclusion criteria were inciting trauma; intracranial tumor; isolated epidural, subdural, intraventricular, or subarachnoid hemorrhage; hemorrhagic transformation of ischemic stroke; and cerebral sinovenous thrombosis. Hospitalization records were abstracted. Follow-up assessments included outcome scores using the Pediatric Stroke Outcome Measure and King’s Outcome Scale for Childhood Head Injury. ICH volumes and total brain volumes were measured by manual tracing. Results— Twenty-two patients, median age 10.3 years (range, 4.2 to 16.6 years), had presenting symptoms of headache in 77%, focal deficits 50%, altered mental status 50%, and seizures 41%. Vascular malformations caused hemorrhage in 91%. Surgical treatment (hematoma evacuation, lesion embolization or excision) was performed during acute hospitalization in 50%. One patient died acutely. At a median follow-up of 3.5 months (range, 0.3 to 7.5 months), 71% of survivors had neurological deficits; 55% had clinically significant disability. Outcome based on Pediatric Stroke Outcome Measure and King’s Outcome Scale for Childhood Head Injury scores was worse in patients with ICH volume >2% of total brain volume ( P =0.023) and altered mental status at presentation ( P =0.005). Conclusions— Spontaneous childhood ICH was due mostly to vascular malformations. Acute surgical intervention was commonly performed. Although death was rare, 71% of survivors had persisting neurological deficits. Larger ICH volume and altered mental status predicted clinically significant disability.

Objective Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS‐CoV‐2 is unknown. This study aimed to determine the proportion of pediatric SARS‐CoV‐2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS‐CoV‐2 in the first 3 months of the pandemic in an international cohort. Methods We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS‐CoV‐2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS‐CoV‐2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS‐CoV‐2 from March 1 to May 31, 2020. Results Of 42 centers with SARS‐CoV‐2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS‐CoV‐2 had ischemic strokes. Proportions of stroke cases positive for SARS‐CoV‐2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS‐CoV‐2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS‐CoV‐2. Seven of 8 patients with SARS‐CoV‐2 had additional established stroke risk factors. Interpretation As in adults, pediatric stroke is an infrequent complication of SARS‐CoV‐2, and SARS‐CoV‐2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS‐CoV‐2 in pediatric stroke better, SARS‐CoV‐2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657–665

Objective Intracerebral hemorrhage (ICH) is a devastating disorder with no current treatment. Whether peri-hematomal edema (PHE) is an independent predictor of neurologic outcome is controversial. We sought to determine whether PHE expansion rate predicts outcome after ICH. Design Retrospective cohort study Setting Tertiary medical center Patients 139 consecutive supratentorial spontaneous ICH patients >18 years admitted between 2000–2013. Interventions None Measurements and Main Results ICH, intraventricular hemorrhage (IVH), and PHE volumes were measured from computed tomography (CT) scans obtained at presentation, 24 hours, and 72 hours post-ICH. PHE expansion rate was the difference between initial and follow-up PHE volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) PHE expansion rate at 24 hours and 90-day mortality and 2) PHE expansion rate at 24 hours and 90-day modified Rankin Scale score (mRS). PHE expansion rate between admission and 24-hours post-ICH was a significant predictor of 90-day mortality (OR 2.97, 95%CI 1.48–5.99, p=0.002). This association persisted after adjusting for all components of the ICH score (OR 2.21, 95% CI 1.05–4.64, p=0.04). Similarly, higher 24-hour PHE expansion rate was associated with poorer mRS in an ordinal shift analysis (OR 2.40, 95% CI 1.37–4.21, p=.002), even after adjustment for all ICH score components (OR 2.07, 95% CI 1.12–3.83, p=0.02). Conclusions Faster PHE expansion rate 24 hours post-ICH is associated with worse outcome. PHE may represent an attractive translational target for secondary injury after ICH.

Background and Purpose-Stroke is an important cause of death and disability among children. Clinical trials for childhood stroke require a valid and reliable acute clinical stroke scale. We evaluated interrater reliability (IRR) of a pediatric adaptation of the National Institutes of Health Stroke Scale. Methods-The pediatric adaptation of the National Institutes of Health Stroke Scale was developed by pediatric and adult stroke experts by modifying each item of the adult National Institutes of Health Stroke Scale for children, retaining all examination items and scoring ranges of the National Institutes of Health Stroke Scale. Children 2 to 18 years of age with acute arterial ischemic stroke were enrolled in a prospective cohort study from 15 North American sites from January 2007 to October 2009. Examiners were child neurologists certified in the adult National Institutes of Health Stroke Scale. Each subject was examined daily for 7 days or until discharge. A subset of patients at 3 sites was scored simultaneously and independently by 2 study neurologists. Results-IRR testing was performed in 25 of 113 a median of 3 days (interquartile range, 2 to 4 days) after symptom onset.Patient demographics, total initial pediatric adaptation of the National Institutes of Health Stroke Scale scores, risk factors, and infarct characteristics in the IRR subset were similar to the non-IRR subset. The 2 raters' total scores were identical in 60% and within 1 point in 84%. IRR was excellent as measured by concordance correlation coefficient of 0.97 (95% CI Key Words: childhood Ⅲ ischemic stroke Ⅲ outcome Ⅲ stroke scale Ⅲ validation I schemic stroke affects 1.2 to 7.9 per 100 000 children aged 1 month to 18 years annually in Europe and North America and ranks among the top 10 causes of death. 1,2 Long-term motor and cognitive deficits interfering with activities of daily life and academic attainment affect 40% to 60% of survivors. 3 There are no proven strategies for acute management or prevention of childhood stroke other than blood transfusion for children with sickle cell anemia. Progress in defining factors that determine outcome and designing clinical trials are hindered by the lack of a validated and reliable clinical stroke scale. Previously published cohort studies of acute clinical presentation or long-term outcome in childhood stroke have not used standardized, validated, and reliable measures of clinical stroke severity at stroke onset. The National Institutes of Health Stroke Scale (NIHSS) is a quantitative measure of stroke-related acute neurological deficit, which has proven intra-and interrater reliability (IRR) and predictive validity for outcome among adults. 4 -6 Neurological examination of children requires adjustment according to the maturation of the child's neurological and cognitive function and ability to comprehend instructions. The objective of this study was to evaluate IRR of a pediatric modification of the NIHSS, the Pediatric NIHSS (PedNIHSS), administered by child neurologists in children with ac...

Background and Purpose-The objective of this study was to describe the occurrence of hemorrhagic transformation (HT) among children with arterial ischemic stroke within 30 days after symptom onset and to describe clinical factors associated with HT. Methods-Sixty-three children aged 1 month to 18 years with arterial ischemic stroke between January 2005 and November 2008 were identified from a single-center prospective pediatric stroke registry. All neuroimaging studies within 30 days of stroke were reviewed by a study neuroradiologist.

Background Perihaematomal oedema (PHE) expansion rate may be a predictor of outcome after intracerebral haemorrhage (ICH). We determined whether PHE expansion rate in the first 72 hours after ICH predicts outcome, and how it compares against other PHE measures. Methods We included patients from the Virtual International Stroke Trials Archive. We calculated PHE expansion rate using the equation: (PHE at 72 hours- PHE at baseline)/(Time to 72 hour computerized tomography scan – Time to baseline computerized tomography scan). Outcomes of interest were mortality and poor 90-day outcome (modified Rankin Scale score of ≥ 3). Logistic regression was used to assess relationships with outcome. Results A total of 596 patients with ICH were included. At baseline, median haematoma volume was 15.0 mL (IQR: 7.9–29.2) with median PHE volume of 8.7 mL (IQR: 4.5–15.5). Median PHE expansion rate was 0.31 mL/hr (IQR: 0.12–0.55). The odds of mortality were greater with increasing PHE expansion rate (OR: 2.63, CI: 1.10–6.25), while the odds of poor outcome also increased with greater PHE growth (OR: 1.67, CI: 1.28–2.39). Female sex had an inverse relationship with PHE growth, but baseline hematoma volume had a direct correlation. Among other PHE measures, only interval increase in PHE correlated with poor outcome. There was no significant difference between the two measures of PHE volume expansion. Conclusions Rate of PHE growth over 72 hours was an independent predictor of mortality and poor functional outcomes following intracerebral haemorrhage. Baseline haematoma volume and gender appear to influence PHE growth.