Background and Purpose—: Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-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 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, 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% confidence interval, 4.6%–10%) at 1 month and 12% (8.5%–15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8–14). The 1-year recurrence rate was 32% (95% confidence interval, 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.

Background and Purpose—: Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods—: Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results—: Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78). Conclusions—: Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Background and Purpose—: Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS. Methods—: In an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS. Results—: Median age at index stroke was 8.2 years (interquartile range, 3.6–14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3–10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies. Conclusions—: Among children with AIS, specific inflammatory biomarkers correlate with cause and—in the arteriopathy group—risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

The syndrome of malignant migrating partial seizures in infancy is a devastating, age‐specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic problem. In this study, we present two patients who were diagnosed with the disease, based on electroclinical symptoms. The patients were treated with a combination of sodium bromide, stiripentol and levetiracetam. The first patient unequivocally responded, following a course of ineffective conventional drugs, and the second, who was diagnosed and treated immediately, showed a more significant therapeutic response. Antiepileptic drugs, previously reported to be beneficial in case reports, when given concomitantly, may substantially reduce the number and severity of seizures, without influence on psychomotor development.[Published with video sequences]

Background and Purpose—: Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection. Methods—: Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test). Results—: One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P =0.998), meningitis (1.348±0.052; n=11; P =0.989), and cardioembolic (1.379±0.056; n=27; P =0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P =0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P =0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections ( P =0.70). Conclusions—: In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.