Cerebral venous sinus (sinovenous) thrombosis (CSVT) in childhood is a rare, but underrecognized, disorder, typically of multifactorial etiology, with neurologic sequelae apparent in up to 40% of survivors and mortality approaching 10%. There is an expanding spectrum of perinatal brain injury associated with neonatal CSVT. Although there is considerable overlap in risk factors for CSVT in neonates and older infants and children, specific differences exist between the groups. Clinical symptoms are frequently nonspecific, which may obscure the diagnosis and delay treatment. While morbidity and mortality are significant, CSVT recurs less commonly than arterial ischemic stroke in children. Appropriate management may reduce the risk of recurrence and improve outcome, however there are no randomized controlled trials to support the use of anticoagulation in children. Although commonly employed in many centers, this practice remains controversial, highlighting the continued need for high-quality studies. This article reviews the literature pertaining to pediatric venous sinus thrombosis.

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Background and Purpose Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported five-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods The Vascular effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009–2014, and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of stroke etiologies, including arteriopathies. Other predictors were measured via parental interview or chart review. Results Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0–3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% CI 4.6–10%) at one month and 12% (8.5–15%) at one year. The sole predictor of recurrence was presence of an arteriopathy, which increased the risk of recurrence 5-fold compared to an idiopathic AIS (hazard ration 5.0, 95% CI 1.8–14). The one-year recurrence rate was 32% (95% CI 18–51%) for moyamoya, 25% (12–48%) for transient cerebral arteriopathy, and 19% (8.5–40%) for arterial dissection. Conclusions Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

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

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Background Epidemiological studies demonstrate that childhood infections, including varicella zoster virus (VZV), are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase risk of childhood AIS. Methods and Results We enrolled 326 centrally-confirmed cases of AIS and 115 stroke-free controls with trauma (ages 29 days-18 years) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7-28 days later) when feasible. Samples were tested by commercial ELISA kits for IgM/IgG antibodies to herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), Epstein Barr virus (EBV), and varicella zoster virus (VZV). An algorithm developed a priori classified serologic evidence of past and acute herpesvirus infection as dichotomous variables. Median (quartiles) age was 7.7 (3.1-14.3) years for cases and 10.7 (6.9-13.2) for controls (p=0.03). Serologic evidence of past infection did not differ between cases and controls. However, serologic evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socio-economic status (OR 2.2; 95% confidence interval, 1.2-4.0; p=0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection, with HSV-1 found most often. Most infections were asymptomatic. Conclusions Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

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Objective: To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke. Methods: We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with 2-year follow-up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at 2 years by the Pediatric Stroke Outcome Measure. Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to 2 years as recovery (improved outcome), emerging deficit (worse outcome), or no change. Results: Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates versus 48.8% of children at discharge compared to 8.0% versus 24.7% after 2 years. Predictors of poor outcome included age between 28 days and 1 year (compared to neonates, odds ratio [OR] = 3.58, p < 0.05), underlying chronic disorder (OR = 2.23, p < 0.05), and involvement of both small and large vascular territories (OR = 2.84, p < 0.05). Recovery patterns differed, with emerging deficits more common in children <1 year of age (p < 0.05). Interpretation: Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and 1 year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke.