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Background: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. Methods: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients Results: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P P =0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P =0.14. Conclusions: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Our goals are (1) to report a consecutive prospective series of children who had posterior circulation stroke caused by vertebral artery dissection at the V3 segment; (2) to describe a configuration of the vertebral artery that may predispose to rotational compression; and (3) to recommend a new protocol for evaluation and treatment of vertebral artery dissection at V3. All children diagnosed with vertebral artery dissection at the V3 segment from September 2014 to July 2020 at our institution were included in the study. Demographic, clinical, surgical, and radiological data were collected. Sixteen children were found to have dissection at a specific segment of the vertebral artery. Fourteen patients were male. Eleven were found to have compression on rotation during a provocative angiogram. All eleven underwent C1C2 posterior fusion as part of their treatment. Their mean age was 6.44 years (range 18 months–15 years). Mean blood loss was 57.7 mL. One minor complication occurred: a superficial wound infection treated with oral antibiotics only. There were no vascular or neurologic injuries. There have been no recurrent ischemic events after diagnosis and/or treatment. Mean follow-up was 33.3 months (range 2–59 months). We designed a new protocol to manage V3 dissections in children. Posterior C1C2 fusion is a safe and effective option for treatment of dynamic compression in vertebral artery dissection in children. Institution of and compliance with a strict diagnostic and treatment protocol for V3 segment dissections seem to prevent recurrent stroke.

Acute pediatric stroke is a medical emergency requiring prompt recognition and treatment because quicker treatment improves neurologic outcomes and reduces excess resource usage on stroke mimics (non-stroke diagnoses). There is a clear need to better differentiate between strokes and their mimics. We performed a single center retrospective cohort study using data from March 1, 2017 to December 31, 2020. We included pediatric patients (> 1m to < 18y) evaluated in the tertiary children’s hospital ED for a stroke team activation. We compared clinical features for patients with stroke and those with a stroke mimic. Of 179 children included in the study (55% female, mean age 11.2y, SD 5.7y), 38 children (21% of total patients, 50% female, mean age 10.5 SD, 6.2 years) were diagnosed with stroke. Strokes included acute ischemic stroke (AIS) (73.7%), hemorrhagic stroke (HS) (18.4%), and cerebral venous sinus thrombosis (CVST) (10.5%). The most common stroke mimics were seizure (14.5%), headache (10.5%), Bell's palsy (5.6%), and conversion disorder (2.7%). Compared to mimics, stroke patients were less likely to have a history of neurosurgery (16.3% mimic vs 2.6% stroke, p=0.028) and more likely to have altered level of alertness (7.7% vs 18.4%, p=0.001), abnormal coordination (15.7% vs 36.4%, p=0.036), abnormal muscle strength (33.1% vs 57.9%, p=0.005) and abnormal reflexes (18.9% vs 43.8%, p=0.018). Of note, there were no significant differences in stroke and mimics for: age, sex, race, ethnicity, basic metabolic panel or CBC, and time from last seen well. Differentiating between strokes and mimics remains difficult without comprehensive diagnostic testing. Our study found that stroke patients are more likely present with altered level of alertness as well as abnormal coordination, muscle strength, and reflexes.

Sturge-Weber syndrome (SWS) is a neurovascular disorder characterized by facial Port-wine stain and intracranial capillary malformations. Patients can have multiple neurological complications including seizures, headaches, and stroke-like episodes, often leading to multiple hospital presentations. Published reports have shown conflicting results on whether patients with SWS with acute neurological complaints have positive imaging findings. Small case reports have described acute ischemic or hemorrhagic changes in SWS patients, whereas larger case series have not identified such imaging findings. Our aim was to report imaging findings in a cohort of SWS patients who presented with acute neurological complaints. We performed a retrospective analysis on all MRI studies performed on SWS patients presenting to our institution with acute neurological symptoms between August 1999 and July 2018. Imaging studies were initially evaluated by the radiologists on-call, and subsequently reviewed by a separate neuroradiologist to confirm the diagnoses. Only studies that were interpreted as having acute findings by both radiologists were counted as positive. During the study period, 23 patients with SWS presented to our institution with acute neurological complaints, of which 13 (56.5%) were male, median age 3 years, with 50 MRI obtained. Seizures were the most common indication for acute imaging (58%), followed by stroke-like episodes (32%), headache (6%), lethargy (2%) and vomiting (2%). Acute changes on MRI were found in 8 studies (16%), with restricted diffusion in 5 patients (of which 4 were presumed to be due to stroke and 1 due to ongoing seizure activity), brain edema in 2 patients and a subdural fluid collection in 1 patient. Of the patients with acute imaging findings, 4 presented with seizures, 3 with stroke-like episodes, and 1 with lethargy. In conclusion, SWS patients with acute neurological complaints can have acute findings on MRI consistent with stroke or other acute injuries. Imaging appears to be an important tool in the management of acute episodes in SWS patients. Restricted diffusion in SWS patients may represent venous congestion or other hemodynamic changes leading to acute injury.

Moyamoya (MMD) is a rare progressive stenosis of anterior cerebral circulation of unknown etiology that occurs at higher prevalence in patients with neurofibromatosis 1, trisomy 21, sickle cell disease (SCD), and East Asians. We hypothesized that vasoactive substances, normally inactivated in the lungs, may escape inactivation through right-to-left shunting and contribute to the development of MMD in at-risk groups. We compared the prevalence of shunting in MMD patients versus controls without MMD. In an IRB-approved, retrospective study we identified 67 MMD patients who had echocardiograms between 1991-2018 and compared the prevalence of potential right-to-left shunting with that of a control group of 123 patients without MMD or stroke from a prior study. In the MMD group, 32 (48%) had potential shunting identified on echocardiogram (23 (34%) intracardiac and 9 (13%) intrapulmonary) versus 29 (24%) potential shunting in our control group (P=0.0006). We also evaluated our MMD patients considering possible bias regarding SCD patients and increased prevalence of pulmonary shunting. In the 43 MMD patients without SCD, 21 (49%) had potential shunting identified on echocardiogram versus 29 (24%) potential shunting in our control group (P=0.0018). In conclusion, these observations support our hypothesis that shunting could contribute to MMD development, possibly through unknown vasoactive substances escaping lung inactivation, subsequently inducing vascular changes in patients with predisposing conditions. This has potential mechanistic and therapeutic implications and will need to be verified in larger prospective studies.

Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small- and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease.We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared.We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS.Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population.

The outcome of children with acute ischemic stroke treated with craniectomy has not been thoroughly examined. In adults, hemicraniectomy after middle cerebral artery territory stroke and posterior decompression after posterior circulation stroke has been shown to improve outcome. Pediatric cases of hemicraniectomy for middle cerebral artery stroke and posterior decompression following posterior circulation stroke suggest relatively good outcome. There are no published data in adults or children with craniectomy after cerebral sinovenous thrombosis. Our aim was to determine the outcome of children with acute ischemic stroke treated with craniectomy in the International Pediatric Stroke Study (IPSS). We included children enrolled who had a craniectomy following stroke presentation. Of 4294 patients in IPSS, 38 children (1%) were found to have craniectomy following an ischemic stroke. Of 38 craniectomy cases, 29 had anterior circulation strokes, 5 had posterior circulation strokes, and 4 had cerebral sinovenous thromboses. The mortality rate was 8%. Overall, children who have craniectomies have significant neurologic deficits. Prospective studies are needed to examine long-term morbidity following craniectomy.

Introduction: Many studies have reported endovascular revascularization therapy (ERT) in children with Childhood Acute Ischemic Stroke (CAIS). With the recent expansion of thrombectomy windows via DAWN/DEFUSE3, more pediatric stroke patients are likely to be potential candidates for intervention. The prevalence of Large Vessel Occlusion (LVO) in the adult population is 25-33% however the prevalence and natural history of LVO in the pediatric population have not yet been described. Methods: This is an IRB approved single center observational study by retrospective chart review of all CAIS who presented acutely to our center from 2004 to 2019. Components of Chart review: Vessel involvement, Mortality/dependency, PSOM and MRS, Etiology, Intervention/Time window of presentation/eligibility for DAWN/DEFUSE, treatment (thrombolysis, ERT), and outcome. Results: 48/218 (22%) of patients with CAIS had an acute presentation consistent with LVO (95% CI 16.7-28.1%). Of the patients with LVO, 23 (46%) were due to large vessel arteriopathy, 15(30%) were cardioembolic, 4 had a hypercoagulable state and 7 were cryptogenic. Ages ranged from day of life 1 to 18 years. 6 (12%) patients died within 2 years of LVO (3 of stroke, 3 from other causes). 5 of the 218 patients reviewed received thrombolysis, with 4/48 LVO patients received thrombolytics. 5/49 LVO patients underwent ERT (4 with at least TICI 2A reperfusion). Average age of LVO patients 14.2 years. PSOM/ comparative outcome data collection is ongoing. Conclusion: Prevalence of LVO has not yet been described in the pediatric population. At our center, 22.4% of CAIS patients had imaging consistent with large vessel occlusion at presentation. This rate is close to that of the adult population (25-33%). Many children have tolerated ERT with good outcomes. Time windows may be less applicable in children given presence of better collaterals and good cardiovascular function. More data is needed regarding the use of advanced imaging modalities for patient stratification in acute neurovascular intervention. Different inclusion criteria may be necessary given improved outcomes among children without intervention.

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 and stroke 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.

We describe 2 previously healthy children who suffered disabling arterial ischemic strokes because of acute intracranial large vessel occlusion within 3 to 4 weeks of coronavirus disease 2019 (COVID-19) infection. Both children presented from communities with high COVID-19 case rates in the Southwest United States. An 8-year-old American Indian girl experienced severe iron deficiency anemia requiring blood transfusion and presented with bilateral middle cerebral artery (MCA) distribution strokes 3 weeks later. She underwent emergent mechanical thrombectomy of the left MCA with successful clot retrieval but experienced reocclusion of that artery 5 hours after intervention. She also had evidence of cerebral arteritis on catheter angiography and vessel wall imaging, and clot pathology revealed recently formed, unorganized platelet- and fibrin-rich thrombus with sparse clusters of erythrocytes, degenerated histiocytes, few eosinophils, and rare neutrophils. A 16-year old African American boy demonstrated evidence of arteritis on brain magnetic resonance angiography and serological markers of cardiac and renal injury accompanied by positive lupus anticoagulant antibodies. The children described in this report express clinical features inconsistent with focal cerebral arteriopathy, including elevated markers of systemic inflammation in both bilateral MCA strokes in one case and multiple organ system dysfunction in the other case. Neither patient fulfilled criteria for multisystem inflammatory syndrome in children, given absence of fever. These cases illustrate that systemic postinfectious arteritis with cerebrovascular involvement may complicate COVID-19 infection in previously healthy school-aged children, and their presentations may overlap but not fulfill criteria for multisystem inflammatory syndrome in children or focal cerebral arteriopathy.

Background and Purpose— The pathogenesis of spontaneous pediatric vertebral artery dissections (VAD) is poorly understood but most often involves the V3 segment where C1 rotates on C2. We studied children with VAD with provocative digital catheter angiography and found an association between VAD and rotational compression. Methods— Seven boys (12 months to 9 years; median 4 years) presented over 38 consecutive months with V3 VAD and underwent digital catheter angiography with provocative passive bilateral neck rotation. Results— VAD were bilateral in 2 patients and unilateral in 5. Provocative digital catheter angiography showed dynamic V3 compression in 6 of 9 dissections, most pronounced or seen only with head rotation to the contralateral side. Two patients had VAD without dynamic compression; both returned 4 months later with a new dissection in a previously normal VA and worsening VAD in 1 patient each. Dynamic compression was also seen in 2 nondissected VA. Surgical management was C1/2 posterior fusion in 5 of 7 patients; 1 underwent unilateral C2 decompression with recurrent VAD and was subsequently fused. Conclusions— The association of dynamic VA compression and VAD at the same level suggests that the compression may contribute to the VAD. However, as dynamic compression was observed in nondissected VA and some VAD were not associated with dynamic compression, VAD may be multifactorial.

Introduction: Pediatric AIS has a high recurrence rate of 10-25%. We observed a high rate of early radiographic recurrence or extension of stroke on repeat MRI performed within 2 weeks of index stroke and hypothesized that early radiographic extension of stroke or recurrent stroke would predict late clinical recurrence. Methods: IRB approved retrospective chart review of children ages 1 week to 18 years with AIS in our institutional pediatric stroke database who had repeat MRI within two weeks of initial acute presentation. We collected clinical and demographic data and reviewed f/u MRI studies for the presence of extension, new stroke, and hemorrhage. Results: 70 patients had early repeat MRI. 23 (33%) had early extension or new stroke on repeat MRI. Of these, 5 (21.7 %) had late clinical recurrence while only 1/47 (2.2%) who did not have early recurrence/extension went on to have late recurrence. 4/70 (5.7 %) had hemorrhagic conversion (only one was symptomatic -headache). Radiographic extension or new stroke on early repeat MRI was significantly associated with late recurrence (p=0.013). Using logistic regression, early extension/recurrence was found to be predictive of late recurrence, (OR 19.5, 95%CI 1.7-228). Conclusion: Children with AIS have a high rate of ongoing early, clinically silent, ischemic injury despite anticoagulation or antiplatelet therapy, which is associated with late clinical recurrence. This early imaging finding may serve as a biomarker that might prove useful as an endpoint in clinical trials comparing early antithrombotic therapies or to identify patients at higher risk of subsequent recurrent overt stroke who might benefit from intensified therapy. Given the high rate of early and late recurrence and low hemorrhage rates from current antithrombotic therapies, more aggressive therapy with dual antithrombotic agents should be investigated.

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is

Background and Purpose— Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods— We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results— Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46–2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29–2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40–2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37–0.93), but the frequency of identified cardiac abnormalities was similar in both groups ( P =0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08–0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55–8.09). Conclusions— Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.

Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.

Stroke in children carries lasting morbidity. Once recognized, it is important to evaluate and treat children with acute stroke efficiently and accurately. All children should receive neuroprotective measures. It is reasonable to consider treatment with advanced thrombolytic and endovascular agents. Delivery of such care requires purposeful institutional planning and organization in pediatric acute care centers. Primary stroke centers established for adults provide an example of the multidisciplinary approach that can be applied to the evaluation and treatment of children who present with acute stroke. The organizational infrastructure of these centers can be employed and adapted for treatment of children with acute stroke. It is likely that care for children with acute stroke can best be delivered by regional pediatric primary stroke centers dedicated to the care of children with pediatric stroke.

Background Schimke immuno-osseous dysplasia is a rare autosomal recessive disease resulting from biallelic SMARCAL1 mutations. It presents in early childhood and is characterized by short stature, nephropathy, and immunodeficiency. Approximately 50% of those affected have neurological complications including migraines, transient ischemic attacks, and strokes. Methods We present a six-year-old boy with Schimke immuno-osseous dysplasia without evidence of atherosclerosis with recurrent episodes of severe headache, fluctuating hemiparesis, and aphasia. Results Magnetic resonance imaging and angiography were normal during the initial episode; multiple areas of reversible restricted diffusion with decreased perfusion and arterial stenosis were seen with subsequent attacks. Conclusions This constellation of symptoms and imaging findings is suggestive of reversible cerebral vasoconstriction syndrome, which we propose as a mechanism for the transient ischemic attacks and infarcts seen in some patients with Schimke immuno-osseous dysplasia, as opposed to accelerated atherosclerosis alone. This new insight may provide a basis for novel preventative therapy in this rare disorder.

Introduction: Cerebral arteriopathies are frequently identified in children with arterial ischemic stroke (AIS), and are distinguished by high stroke recurrence. However, the clinical and neuroimaging profiles of AIS due to cerebral arteriopathy versus non- arteriopathy have not been compared. Hypothesis: We hypothesized that children with AIS due to arteriopathy would differ in their demographic, clinical, and radiographic presentation from those without arteriopathy. Methods: We report a large, prospective, multicentre cohort of children, 1 month - 17 years, with AIS, enrolled in the International Pediatric Stroke Study, 2003-2014. Those with arteriopathy including focal cerebral arteriopathy, dissection, moyamoya, vasculitis and non-specific arteriopathies, were compared to those with non-arteriopathic stroke etiologies. Results: Of 2127 children with AIS, 725(34%) had arteriopathy (58% male, mean age 8.1years). The remaining 1402(66%) had non-arteriopathic AIS. Arteriopathy was associated with older age, but not a specific gender or ethnicity. Geographic differences were observed. Children with arteriopathy were likely to present with hemiparesis, dysarthria, ataxia, headache, preceding/concurrent thromboembolic events and without seizures. Risk factors associated with arteriopathy included sickle anemia, head/neck trauma and lack of acute systemic disease. Radiological associations with arteriopathy included right sided unilateral or bilateral stroke, multiple infarcts and relative reduction in occurrence of intracranial hemorrhage. On multivariate analysis, headache (p=0.006), additional thromboembolic events (p=0.007), multiple infarcts (p=0.002) and lack of seizures (p=0.001) were independently associated with arteriopathy. Conclusions: Specific clinical profiles are associated with arteriopathy in children with AIS and may guide the clinician in early diagnostic evaluations and management.

Introduction: Stroke is reported among the top 10 causes of death in children in the US. In the Kids’ Inpatient Database, older age and Hispanic ethnicity were risk factors for mortality after pediatric ICH. Limited data is available regarding risk factors for death after pediatric arterial ischemic stroke (AIS). Objective: To identify predictors of in-hospital mortality in pediatric patients hospitalized with AIS. Methods: Neonates (0-28 days) and children (29 days- Results: Fourteen of 915 neonates (1.5%) and 74/2,285 children (3.2%) died during hospitalization. Of 54 cases with reported causes of death, 32 (59%) were related to AIS (herniation 2, brain death 10, ICH/hemorrhagic transformation 5, care withdrawal due to stroke severity 15), with the remaining deaths attributed to underlying medical disease. Of 356 children with Pediatric NIH Stroke Scale (PedNIHSS) scores, median PedNIHSS was 19 (IQR 14-27) among the 13 children who died and 7 (IQR 3-12) among the 343 children who did not die. In multivariable analysis, congenital heart disease (OR 4.1, 95%CI 1.3-13, p=0.018) and posterior plus anterior circulation stroke (OR 4.3, 95%CI 1.3-14, p=0.017) were associated with in-hospital mortality for neonates, while higher PedNIHSS [OR 1.11 (per 1 point PedNIHSS increase), 95%CI 1.03-1.19, p=0.004], Hispanic ethnicity (OR 7.6, 95%CI 1.8-32.3, p=0.006), and cardiac disease (OR 7.5, 95%CI 1.5-38.6, p=0.015) were associated with in-hospital mortality for children. Conclusions: In-hospital mortality occurred in about 2% of pediatric AIS cases with nearly 60% attributable to stroke. Risk factors for in-hospital mortality included cardiac disease and stroke severity, factors also associated with mortality in adults. Hispanic ethnicity, a factor associated with mortality in childhood ICH, was also associated with mortality after childhood AIS; the underlying reasons are unclear. Additional information is needed on stroke-related deaths after hospitalization.

Introduction: Acute symptomatic seizures are common after pediatric arterial ischemic stroke (AIS). We sought to analyze practice variation in anticonvulsant medication treatment (ACM) after AIS. We hypothesized that ACM practice varies but is related to age, acute seizure frequency and duration, cortical involvement, and hemorrhagic conversion. Methods: Seizures in Pediatric Stroke (SIPS), an international, prospective study, enrolled neonatal ( Results: Among 116 patients, 27 neonates and 31 children (ages 0.2-17 years) had an acute seizure. In neonates, 24 (89%) had ACM continued after discharge, but only 4 (15%) remained on ACM at 12 m (3 having had post-discharge seizure). Phenobarbital was the most common ACM in neonates at discharge (n=14) and 12m (n=2, levetiracetam = 2). In children, 23 (74%) had ACM at discharge, and 17 (57%) remained on ACM at 12m (7 having had a post-discharge seizure). All patients in study with post-discharge seizure were discharged on ACM. Two neonates and 1 child with post-discharge seizure were not on ACM at 12m. Levetiracetam was the most common ACM in children at discharge (n=11) and 12m (n=9). No single variable correlated with discharge ACM (Table). ACM at 12 m correlated with neonatal stroke, >10 seizures in acute period, and post-discharge seizure. In logistic regression, all variables remained significant. Conclusion: ACM management after acute post-stroke seizures varies widely in pediatric stroke. Neonates rarely, but children frequently, are continued on ACM up to 1 year, even without further seizures.

© 2015 Elsevier Inc. All rights reserved. Background Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke. Results Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research. Conclusions There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.

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.

Professional societies recommend screening lipids in healthy children. Dyslipidemia and elevated lipoprotein(a) are risk factors for adult cardiovascular disease and stroke. Their role in childhood arterial ischemic stroke is unexplored. Inconsistencies in testing limit analysis of existing lipid data. The objective of this study is to identify predictors and modifiable barriers to lipid testing in pediatric stroke.In this cross-sectional analysis, children (28 days-18 years) with arterial ischemic stroke were identified from the International Pediatric Stroke Study registry (January 2003-April 2012). Analyzed predictors of recorded lipid or lipoprotein a (Lp(a)) testing were age, sex, race, ethnicity, body mass index (BMI) category, other stroke risk factors, country, US region, and recurrent thrombosis.Among 1652 participants (median, 6 years [interquartile range, 1.7-12.7]; 59.0% male; 40.8% white; 7.0% black), at least 1 lipid parameter or Lp (a) was available for 461 (27.9%). Compared with infants, testing was incrementally higher for older age categories. Compared with whites, testing was lower in blacks (adjusted odds ratio [OR], .5; 95% confidence interval [CI], .4-.5; P.0001). Hispanic ethnicity only predicted testing within the United States (OR, 2.2; 95% CI, 1.4-3.4; P = .001]. Testing was lower in the United States and Australia and higher in Chile. Any thrombotic recurrence and recurrent symptomatic arterial ischemic stroke were associated with testing, unlike male sex, BMI, other stroke risk factors, and region in the United States.Only a quarter of children with stroke had recorded lipid testing. Older age, white race, and recurrence predicted testing. In future study adjusting for these predictors may be necessary. Standardized lipid testing in children with arterial ischemic stroke may further our understanding of this potential risk factor.

Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia.

Children with sickle cell anemia have a high prevalence of silent cerebral infarcts (SCIs) that are associated with decreased full-scale intelligence quotient (FSIQ). While the educational attainment of parents is a known strong predictor of the cognitive development of children in general, the role of parental education in sickle cell anemia along with other factors that adversely affect cognitive function (anemia, cerebral infarcts) is not known. We tested the hypothesis that both the presence of SCI and parental education would impact FSIQ in children with sickle cell anemia. A multicenter, cross-sectional study was conducted in 19 US sites of the Silent Infarct Transfusion Trial among children with sickle cell anemia, age 5-15 years. All were screened for SCIs. Participants with and without SCI were administered the Wechsler Abbreviated Scale of Intelligence. A total of 150 participants (107 with and 43 without SCIs) were included in the analysis. In a multivariable linear regression model for FSIQ, the absence of college education for the head of household was associated with a decrease of 6.2 points (P = 0.005); presence of SCI with a 5.2 point decrease (P = 0.017); each $1000 of family income per capita with a 0.33 point increase (P = 0.023); each increase of 1 year in age with a 0.96 point decrease (P = 0.023); and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point decrease (P = 0.030). In conclusion, FSIQ in children with sickle cell anemia is best accounted for by a multivariate model that includes both biologic and socioenvironmental factors.

Potential clinical barriers to making a timely diagnosis of pediatric brainstem stroke and pitfalls of noninvasive vascular imaging are presented.An institutional review board-approved institutional database query from 2001-2012 yielded 15 patients with brainstem strokes. Medical records were reviewed for symptoms, stroke severity using the Pediatric National Institutes of Health Stroke Scale, and outcomes using the Pediatric Stroke Outcome Measure. Magnetic resonance angiography was compared with digital subtraction angiography.There were 10 boys and five girls; 9 months to 17 years of age (mean 7.83 years). Symptoms were headaches (eight); visual problems (eight), seizure-like activity (seven), motor deficits (six), and decreased level of consciousness in four. Time since last seen well was 12 hours to 5 days. Pediatric National Institutes of Health Stroke Scale was 1-34;10 in eight; 3 in 1, 10-20 in two, and20 in four. Strokes were pontine in 13/15 and involved50% of the pons in six and50% in seven; 2/15 had medullary strokes. Magnetic resonance angiography showed basilar artery occlusion in 8/13 patients and vertebral artery dissection in two. Digital subtraction angiography done within 9-36 hours of magnetic resonance angiography in 10/15 patients confirmed the basilar artery occlusion seen by magnetic resonance angiography and showed vertebral artery dissection in four patients. Patients were systemically anticoagulated without hemorrhagic complications. One patient died. Pediatric Stroke Outcome Measures at 2-36 months is 0-5.0/10 (mean 1.25).Vague symptoms contributed to delays in diagnosis. Magnetic resonance angiography was equivalent to digital subtraction angiography for basilar artery occlusion but not for vertebral artery dissection. Even with basilar artery occlusion and high stroke scales, outcome was good when systemic anticoagulation was started promptly.

Introduction: Childhood cerebral arteriopathies are heterogeneous and difficult to classify. Our goal was to identify clinical and imaging biomarkers associated with subtypes of childhood arteriopathy in order to facilitate their diagnosis and classification in both research and clinical settings. Methods: From 2009-2014, the VIPS study enrolled 355 children (age 29d-18y) with arterial ischemic stroke. A neuroradiologist and pediatric vascular neurologist independently reviewed vascular imaging and clinical data to diagnose arteriopathy (none, possible, definite), and then classify arteriopathy subtype: arterial dissection, transient cerebral arteriopathy (TCA), moyamoya, and secondary vasculitis. Disagreements were resolved through discussion by a panel of two neuroradiologists and two pediatric vascular neurologists. We constructed multivariable logistic regression models to identify characteristics independently associated with each subtype. Results: Of 127 cases with definite arteriopathy, 109 received a single arteriopathy subtype diagnosis (26 dissection, 25 TCA, 34 moyamoya, 15 secondary vasculitis, and 9 “other”), while 18 were of indeterminate subtype. There were no cases of primary vasculitis. Independent predictors of arteriopathy subtype are shown (Table). The association between black race and moyamoya is explained by sickle cell anemia. A banding pattern on the vascular imaging was pathognomonic of TCA. Moyamoya and vasculitis secondary to meningitis had similar distal internal carotid artery abnormalities, but lenticulostriate collaterals suggested moyamoya, and a decreased level of consciousness predicted secondary vasculitis. Conclusions: The different subtypes of childhood arteriopathies are associated with typical clinical, parenchymal and vascular imaging features that can help narrow the differential diagnosis in pediatric stroke patients with vascular abnormalities.

Introduction: Headache is common at onset of arterial ischemic stroke (AIS), with rates between 10-50%. Adult studies suggest that headache prevalence relates to stroke etiology, with highest rates observed in dissection. We hypothesized that children with arteriopathy-related stroke may have higher rates of headache than those without. Methods: Children (29 days -18 years) with AIS enrolled in the prospective, international Vascular Effects of Infection in Pediatric Stroke (VIPS) study were analyzed for presence of headache at stroke ictus. Cases were subjected to a rigorous, centralized process for diagnostic confirmation of AIS and radiographic classification of arteriopathy as definite, possible or absent. Site investigators abstracted data from medical records regarding stroke presentation details. Headache at stroke ictus was classified as present, absent or unclear. Results: We included all 355 VIPS cases in this secondary analysis. Headache was uncommon in subjects < 3 yo (5/90, 6%) but was present in nearly half of those ≥ 3 yo (108/265, 46%). Excluding those with an unclear headache presentation (n=31), there was no significant difference in headache at stroke ictus in children ≥ 3 yo with definite (46/92, 50%), possible (15/24, 63%) or absent (60/118, 51%) arteriopathy (p=0.53). However, in those with definite arteriopathy, a difference was found in sub-classification, with headache prevalence highest in dissection and transient cerebral arteriopathy of childhood (TCA) (70% each) (p>0.001). Acute headache was uncommon in children with moyamoya (12%). Conclusion: No difference was found in headache prevalence in children with and without definite or possible arteriopathy. However, in children with definite arteriopathy, headache was more common in TCA and dissection. This may reflect a higher degree of nociceptive afferent activation in these childhood AIS subtypes and may provide clues to underlying pathophysiologic mechanisms.

Background and Purpose— There are limited data about the reliability of subtype classification in childhood arterial ischemic stroke, an issue that prompted the IPSS (International Pediatric Stroke Study) to develop the CASCADE criteria (Childhood AIS Standardized Classification and Diagnostic Evaluation). Our purpose was to determine the CASCADE criteria’s reliability in a population of children with stroke. Methods— Eight raters from the IPSS reviewed neuroimaging and clinical records of 64 cases (16 cases each) randomly selected from a prospectively collected cohort of 113 children with arterial ischemic stroke and classified them using the CASCADE criteria. Clinical data abstracted included history of present illness, risk factors, and acute imaging. Agreement among raters was measured by unweighted κ statistic. Results— The CASCADE criteria demonstrated a moderate inter-rater reliability, with an overall κ statistic of 0.53 (95% confidence interval [CI]=0.39–0.67). Cardioembolic and bilateral cerebral arteriopathy subtypes had much higher agreement (κ=0.84; 95% CI=0.70–0.99; and κ=0.90; 95% CI=0.71–1.00, respectively) than cases of aortic/cervical arteriopathy (κ=0.36; 95% CI=0.01–0.71), unilateral focal cerebral arteriopathy of childhood (FCA; κ=0.49; 95% CI=0.23–0.76), and small vessel arteriopathy of childhood (κ=−0.012; 95% CI=−0.04 to 0.01). Conclusions— The CASCADE criteria have moderate reliability when used by trained and experienced raters, which suggests that it can be used for classification in multicenter pediatric stroke studies. However, the moderate reliability of the arteriopathic subtypes suggests that further refinement is needed for defining subtypes. Such revisions may reduce the variability in the literature describing risk factors, recurrence, and outcomes associated with childhood arteriopathy.

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, 0.94 to 0.99); intraclass correlation coefficient of 0.99 (95% CI, 0.97 to 0.99); precision measured by Pearson ρ of 0.97; and accuracy measured by the bias correction factor of 1.0. Conclusions— There was excellent IRR of the pediatric adaptation of the National Institutes of Health Stroke Scale in a multicenter prospective cohort performed by trained child neurologists.

In adults, patent foramen ovale or other potential intracardiac shunts are established risk factors for stroke via paradoxical embolization. Stroke is less common in children and risk factors differ. The authors examined the literature on intracardiac shunting and stroke in children, identifying the methods employed, the prevalence of detectible intracardiac shunts, associated conditions, and treatments. PubMed searches with keywords related to intracardiac shunting and stroke in children identified articles of interest. Additional articles were identified via citations in these articles or in reviews. The authors found that studies of intracardiac shunting in children with stroke are limited. No controlled studies were identified. Detection methods vary and the prevalence of echocardiographically detectible intracardiac shunting appears lower than reported in adults and autopsy studies. Defining the role of intracardiac shunting in pediatric stroke will require controlled studies with unified detection methods in populations stratified by additional risk factors for paradoxical embolization. Optimal treatment is unclear.

Silent cerebral infarctions (SCI) occur in up to 35% of children with sickle cell anemia (HbSS) but are rarely recognized during the initial 10–14 days when diffusion weighted magnetic resonance imaging (MRI) can differentiate acute infarctions from remote events. We report acute SCI in seven children with HbSS who had areas of restricted diffusion on MRI without persistent focal neurologic deficits. Four had acute SCI identified following acute anemic events. Our observations suggest that SCI are detectible in the acute phase, present with subtle neurologic symptoms, result in permanent neurologic injury, and may be caused by acute anemic events. Pediatr Blood Cancer 2010;54:461–464. © 2009 Wiley-Liss, Inc.

Steady-state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO(2)) and cerebral artery blood flow velocity measured by transcranial Doppler ultrasonography (TCD), an established risk factor for overt stroke in Hb SS. We studied 181 children using multivariate models to control for known determinants of TCD velocity, including age, haematocrit, and a measure of stenosis. We found that SpO(2) correlated significantly and inversely with TCD velocity in both the right and left middle cerebral arteries. Hb desaturation was associated with increased cerebral artery blood flow velocities and increased odds of abnormal TCD velocities, hence increased risk of stroke. About 5% of the variation in TCD velocity could be ascribed to Hb saturation while controlling for other determinants of TCD velocity. In conclusion, Hb saturation is a determinant of TCD velocity and a risk factor for stroke in children with Hb SS.

Background Diffusion-weighted imaging magnetic resonance imaging may detect changes in brain structures remote but connected to stroke consistent with neuropathological descriptions of diaschisis. Early diffusion-weighted imaging demonstrates restriction in corticospinal pathways after arterial ischemic stroke of all ages that correlates with motor outcome. Aim/hypothesis We hypothesized that cerebral diaschisis is measurable in childhood arterial ischemic stroke and explored associations with outcome. Methods This sub-study of the validation of the Pediatric NIH Stroke Scale study prospectively enrolled children with acute arterial ischemic stroke and both acute and early follow-up (5–14 days) diffusion-weighted imaging. Inclusion criteria were (1) unilateral middle cerebral artery arterial ischemic stroke, (2) acute and subacute diffusion-weighted imaging ( b = 1000), and (3) 12 month neurological follow-up (Pediatric Stroke Outcome Measure). A validated method using ImageJ software quantified diffusion-weighted imaging diaschisis in anatomically connected structures. Diaschisis measures were corrected for infarct volume, compared to age, imaging timing, and outcomes (Chi square/Fisher, Mann–Whitney test). Results Nineteen children (53% male, median 8.1 years) had magnetic resonance imaging at medians of 21 and 168 h post-stroke onset. Diaschisis was common and evolved over time, observed in one (5%) on acute but eight (42%) by follow-up diffusion-weighted imaging. Thalamic and callosal diaschisis were most common (5, 26%). Estimates of perilesional diaschisis varied (54 ± 18% of infarct volume). Children with diaschisis tended to be younger (7.02 ± 5.4 vs. 11.82 ± 4.3 years, p = 0.08). Total diaschisis score was associated with poor cognitive outcomes ( p = 0.03). Corticospinal tract diaschisis was associated with motor outcome ( p = 0.004). Method reliability was excellent. Conclusions Diffusion-weighted imaging diaschisis occurs in childhood arterial ischemic stroke. Mistaking diaschisis for new areas of infarction carries important clinical implications. Improved recognition and study are required to establish clinical relevance.

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 Childhood arterial ischemic stroke is an important cause of morbidity and mortality in children. Hyperacute treatment strategies remain controversial and challenging, especially in the setting of increasingly proven medical and endovascular options in adults. Although national and international pediatric guidelines have given initial direction about acute therapy and management, pediatric centers have traditionally lacked the infrastructure to triage, diagnose, and treat childhood arterial ischemic stroke quickly. Methods In the past 10 years, researchers in the International Pediatric Stroke Study and Thrombolysis in Pediatric Stroke study have initiated early strategies for establishing pediatric specific stroke alerts. Results We review the rationale, process and components necessary for establishing a pediatric stroke alert. Conclusion Development of pediatric stroke protocols and pathways, with evidence-based acute management strategies and supportive care where possible, facilitates the evaluation, management, and treatment of an acute pediatric stroke.

In this issue of Blood , Bernaudin et al have identified the rate of acute anemic events (AAEs) and extracranial internal carotid artery (ICA) stenosis as risk factors for silent cerebral infarcts (SCIs) in children with sickle cell anemia (SCA).[1][1] SCIs refer to permanent brain lesions, usually

We report 19 patients with a previously undelineated neurodegenerative syndrome characterized by episodic acute onset of irritability or neurological deficits between 2 months and 3.5 years of age, followed by steady or intermittent clinical deterioration. Seven children died between 11 months and 14 years of age. Cranial magnetic resonance imaging (MRI) shows patchy leukoencephalopathy with cavities, and vascular permeability, in actively affected regions. Early lesions affect corpus callosum and centrum semiovale, with or without cerebellar or cord involvement. After repeated episodes, areas of tissue loss coalesce with older lesions to become larger cystic regions in brain or spinal cord. Diffuse spasticity, dementia, vegetative state, or death ensues. Gray matter is spared until late in the course. In some, incomplete clinical or MRI recovery occurs after episodes. The clinical course varies from rapid deterioration to prolonged periods of stability that are unpredictable by clinical or MRI changes. Elevated levels of lactate in brain, blood, and cerebrospinal fluid, abnormal urine organic acids, and changes in muscle respiratory chain enzymes are present but inconsistent, without identifiable mitochondrial DNA mutations or deletions. Pathological studies show severe loss of myelin sparing U-fibers, axonal disruption, and cavitary lesions without inflammation. Familial occurrence and consanguinity suggest autosomal recessive inheritance of this distinct entity.