Health Inequity and Time From Pediatric Stroke Onset to Arrival.

BACKGROUND: Time from stroke onset to hospital arrival determines treatment and impacts outcome. Structural, socioeconomic, and environmental factors are associated with health inequity and onset-to-arrival in adult stroke. We aimed to assess the association between health inequity and onset-to-arrival in a pediatric comprehensive stroke center. METHODS: A retrospective observational study was conducted on a consecutive cohort of children (>28 days-18 years) diagnosed with acute arterial ischemic stroke (AIS) between 2004 and 2019. Neighborhood-level material deprivation was derived from residential postal codes and used as a proxy measure for health inequity. Patients were stratified by level of neighborhood-level material deprivation, and onset-to-arrival was categorized into 3 groups: <6, 6 to 24, and >24 hours. Association between neighborhood-level material deprivation and onset-to-arrival was assessed in multivariable ordinal logistic regression analyses adjusting for sociodemographic and clinical factors. RESULTS: Two hundred and twenty-nine children were included (61% male; median age [interquartile range] at stroke diagnosis 5.8-years [1.1-11.3]). Over the 16-year study period, there was an increase in proportion of children diagnosed with AIS living in the most deprived neighborhoods and arriving at the emergency room within 6 hours (P=0.01). Among Asian patients, a higher proportion lived in the most deprived neighborhoods (P=0.02) and level of material deprivation was associated with AIS risk factors (P=0.001). CONCLUSIONS: Our study suggests an increase in pediatric stroke in deprived neighborhoods and certain communities, and earlier arrival times to the emergency room over time. However, whether these changes are due to an increase in incidence of childhood AIS or increased awareness and diagnosis is yet to be determined. The association between AIS risk factors and material deprivation highlights the intersectionality of clinical factors and social determinants of health. Finally, whether material deprivation impacts onset-to-arrival is likely complex and requires further examination.

The development of the pediatric stroke neuroimaging platform (PEDSNIP).

Childhood stroke occurs from birth to 18 years of age, ranks among the top ten childhood causes of death, and leaves lifelong neurological impairments. Arterial ischemic stroke in infancy and childhood occurs due to arterial occlusion in the brain, resulting in a focal lesion. Our understanding of mechanisms of injury and repair associated with focal injury in the developing brain remains rudimentary. Neuroimaging can reveal important insights into these mechanisms. In adult stroke population, multi-center neuroimaging studies are common and have accelerated the translation process leading to improvements in treatment and outcome. These studies are centered on the growing evidence that neuroimaging measures and other biomarkers (e.g., from blood and cerebrospinal fluid) can enhance our understanding of mechanisms of risk and injury and be used as complementary outcome markers. These factors have yet to be studied in pediatric stroke because most neuroimaging studies in this population have been conducted in single-centred, small cohorts. By pooling neuroimaging data across multiple sites, larger cohorts of patients can significantly boost study feasibility and power in elucidating mechanisms of brain injury, repair and outcomes. These aims are particularly relevant in pediatric stroke because of the decreased incidence rates and the lack of mechanism-targeted trials. Toward these aims, we developed the Pediatric Stroke Neuroimaging Platform (PEDSNIP) in 2015, funded by The Brain Canada Platform Support Grant, to focus on three identified neuroimaging priorities. These were: developing and harmonizing multisite clinical protocols, creating the infrastructure and methods to import, store and organize the large clinical neuroimaging dataset from multiple sites through the International Pediatric Stroke Study (IPSS), and enabling central searchability. To do this, developed a two-pronged approach that included building 1) A Clinical-MRI Data Repository (standard of care imaging) linked to clinical data and longitudinal outcomes and 2) A Research-MRI neuroimaging data set acquired through our extensive collaborative, multi-center, multidisciplinary network. This dataset was collected prospectively in eight North American centers to test the feasibility and implementation of harmonized advanced Research-MRI, with the addition of clinical information, genetic and proteomic studies, in a cohort of children presenting with acute ischemic stroke. Here we describe the process that enabled the development of PEDSNIP built to provide the infrastructure to support neuroimaging research priorities in pediatric stroke. Having built this Platform, we are now able to utilize the largest neuroimaging and clinical data pool on pediatric stroke data worldwide to conduct hypothesis-driven research. We are actively working on a bioinformatics approach to develop predictive models of risk, injury and repair and accelerate breakthrough discoveries leading to mechanism-targeted treatments that improve outcomes and minimize the burden following childhood stroke. This unique transformational resource for scientists and researchers has the potential to result in a paradigm shift in the management, outcomes and quality of life in children with stroke and their families, with far-reaching benefits for other brain conditions of people across the lifespan.

Cerebral Arteriopathies of Childhood - Current Approaches.

Up to more than half of previously healthy children presenting with their first arterial ischemic stroke have a cerebral arteriopathy. Cerebral arteriopathies during childhood can be congenital, reflecting abnormal vessel development, or acquired when caused by disruption of vascular homeostasis. Distinguishing different types of cerebral arteriopathies in children can be challenging but of great clinical value as they may dictate different disease and treatment courses, and clinical and radiologic outcomes. Furthermore, children with stroke due to a specific arteriopathy exhibit distinctive features when compared to those with stroke due to other causes or a different type of arteriopathy. These features become crucial in the management of pediatric stroke by choosing appropriate diagnostic and treatment strategies. The objective of this article is to provide the reader with a comprehensive up-to-date review of the classification, symptoms, diagnosis, treatment, and outcome of cerebral arteriopathies in children.

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children.

Pediatric low-grade gliomas (PLGGs) are the most common central nervous system (CNS) tumors in children. The current standard of care for surgically unresectable and/or progressive cases of PLGGs includes combination chemotherapy. PLGGs are molecularly characterized by alterations in the RAS/RAF/MAPK/ERK pathway in a majority of tumors. PLGGs harboring the BRAF-V600E mutation respond poorly to current chemotherapy strategies. We present a case of a two-year-old female with biopsy-proven low-grade glioma (LGG, pilocytic astrocytoma) involving the hypothalamic/optic chiasm region. At presentation, she had obstructive hydrocephalus, bitemporal hemianopia, central hypothyroidism, and right-sided hemiparesis due to the location/mass effect of the tumor. She was initially treated with chemotherapy (vincristine/carboplatin), but her tumor progressed at six weeks of treatment. She was subsequently started on dabrafenib as her tumor was positive for BRAF-V600E mutation. Dabrafenib monotherapy resulted in dramatic improvement in her clinical symptoms and near-complete resolution of tumor. Our experience and review of the literature suggest that LGGs with BRAF-V600E mutations may benefit from upfront targeted therapy in children. There is an urgent need for prospective clinical trials comparing the efficacy of upfront BRAF inhibitors versus standard chemotherapy in PLGGs with BRAF mutations.

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

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.

Association of outcomes in acute flaccid myelitis with identification of enterovirus at presentation: a Canadian, nationwide, longitudinal study.

BACKGROUND: Acute flaccid myelitis (AFM) is characterised by rapid onset of limb weakness with spinal cord grey-matter abnormalities on MRI scan. We aimed to assess whether detection of enterovirus in respiratory or other specimens can help predict prognosis in children with AFM. METHODS: In this nationwide, longitudinal study, we evaluated the significance of detection of enterovirus in any sample in predicting outcomes in a cohort of Canadian children younger than 18 years presenting with AFM to tertiary paediatric hospitals in Canada in 2014 and 2018. All patients fulfilled the 2015 US Centers for Disease Control and Prevention case definition for definite AFM or probable AFM. Clinical data, laboratory findings, treatment, and neuroimaging results were collected (follow up period up to 5 years). We assessed neurological function and motor outcomes using Kurtzke's Expanded Disability Status Scale (EDSS) and a Weakest Limb Score. FINDINGS: 58 children with AFM (median age 5·1 years, IQR 3·8-8·3) were identified across five of Canada's ten provinces and three territories. 25 (43%) children had enterovirus detected in at least one specimen: 16 (64%) with EV-D68, two (8%) with EV-A71, two (8%) with coxsackievirus, 10 (40%) with untyped enterovirus. Children who were enterovirus positive were more likely than those that were negative to have had quadriparesis (12 [48%] of 25 vs four [13%] of 30; p=0·028), bulbar weakness (11 [44%] of 25 vs two [7%] of 30; p=0·028), bowel or bladder dysfunction (14 [56%] of 25 vs seven [23%] of 30; p=0·040), cardiovascular instability (nine [36%] of 25 vs one [3%] of 30; p=0·028), and were more likely to require intensive care unit admission (13 [52%] of 25 vs 5 [17%] of 30; p=0·028). On MRI, most children who were enterovirus positive showed brainstem pontine lesions (14 [61%] of 23), while other MRI parameters did not correlate with enterovirus status. Median EDSS of enterovirus positive (EV+) and enterovirus negative (EV-) groups was significantly different at all timepoints: baseline (EDSS 8·5, IQR 4·1-9·5 vs EDSS 4·0, IQR 3·0-6·0; p=0·0067), 3 months (EDSS 4·0, IQR 3·0-7·4 vs EDSS 3·0, IQR 1·5-4·3; p=0·0067), 6 months (EDSS 3·5, IQR 3·0-7·0 vs EDSS 3·0, IQR 1·0-4·0; p=0·029), and 12 months (EDSS 3·0, IQR 3·0-6·9 vs EDSS 2·5 IQR 0·3-3·0; p=0·0067). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children who tested positive for enterovirus than for those who tested negative (p=0·037). INTERPRETATION: Detection of enterovirus in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. These results have implications for rehabilitation planning as well as counselling of families of children with these disorders. The findings of this study support the need for early testing for enterovirus in non-CNS sites in all cases of AFM. FUNDING: None.

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

OBJECTIVE: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features. METHODS: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes. RESULTS: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions. CONCLUSION: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

Predicting Recovery and Outcome after Pediatric Stroke: Results from the International Pediatric Stroke Study.

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. ANN NEUROL 2020;87:840-852.

Comparative study of posterior and anterior circulation stroke in childhood: Results from the International Pediatric Stroke Study.

OBJECTIVE: To compare risk factors, clinical presentation, and outcomes after posterior circulation arterial ischemic stroke (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children. METHODS: In this international multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), we compared clinical and radiologic features according to stroke location. RESULTS: Of 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% vs 22%, p < 0.001). Children with PCAIS were older than children with ACAIS (median age 7.8 [interquartile range (IQR) 3.1-14] vs 5.1 [IQR 1.5-12] years, p < 0.001), and more often presented with headache (54% vs 32%, p < 0.001) and a lower Pediatric NIH Stroke Scale score (4 [IQR 2-8] vs 8 [IQR 3-13], p = 0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% vs 8.5%, p < 0.001), while cardioembolic strokes were less frequent (19% vs 32%, p < 0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurologic examination at hospital discharge in 29% vs 21%, p = 0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates. CONCLUSION: PCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older and have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS.

Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children.

OBJECTIVE: We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Craniocervical Arterial Dissection in Children: Pathophysiology and Management.

BACKGROUND: Craniocervical arterial dissection is a commonly reported arteriopathy associated with stroke in children. It is characterized by a high stroke recurrence rate and variable outcomes. Here we review the pathophysiology, clinical presentation, and diagnostic neuroimaging approaches that are helpful in accurate diagnosis and follow-up of children with arterial dissection. METHODS: MEDLINE searches (2000 to 2018) for articles that contained patients aged less than 18 years with craniocervical arterial dissection was performed, with the goal of analyzing their presenting features, pathophysiological mechanisms, and imaging characteristics and interventions. RESULTS: Sixteen articles met the study criteria and reported 182 cases of craniocervical arterial dissection, 68% male, average age 8.6 years. Dissection was associated with head and neck trauma in 56% of the cases and frequently involved the posterior (61%) and extracranial locations (64%); the vertebral artery was the most commonly involved artery (60%). The most common clinical presentation was hemiparesis (80/160, 50%), followed by headache (64/164, 39%). Magnetic resonance imaging was the preferred neuroimaging method, followed by cerebral catheter angiography as a gold standard definitive neurovascular imaging modality when the initial vascular imaging revealed nondiagnostic findings. CONCLUSIONS: The diagnosis of arterial dissection requires a high index of suspicion and consideration for detailed neurovascular imaging, including both the cranial and cervical regions. Neurovascular imaging challenges, especially visualization of arterial abnormalities, highlight the importance of appropriate and timely use of specific neurovascular imaging techniques. Magnetic resonance imaging appears to be the preferred neurovascular imaging modality in children with arterial dissection and may obviate the need for invasive cerebral catheter angiography.

Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History.

Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.

Epidemiology, Clinical Presentation, and Prognosis of Posterior Circulation Ischemic Stroke in Children.

BACKGROUND: Anterior and posterior circulation strokes are often different in terms of presentation and recurrence risk, but there are few studies that focused on posterior circulation stroke. METHODS: We performed a longitudinal retrospective study of children, birth to 18 years, with posterior circulation ischemic stroke at the Children's Hospital Winnipeg from January 1992 to December 2012. Clinical and radiological features and outcomes were collected using standardized tools. RESULTS: Of the 158 children with arterial ischemic stroke, 23 (14.5%) children, 21 non-neonates, and 11 males were identified. For posterior circulation ischemic stroke, mean crude incidence of 0.38 and crude mortality rate of 0.11 per 100,000 person-years was estimated. The crude total period prevalence rate for the study period was estimated as 8.1 per 100,000 children. Nonspecific symptoms before stroke presentation were present in 38% and impaired consciousness in 71%. Identifiable risk factors were present in two thirds: vasculopathy 24%, infection 19%, trauma 14%, and congenital heart disease 9.5%. Average Pediatric National Institutes of Health Stroke Scale score at presentation was 11. Poor outcome was noted in 45%. Outcome did not change significantly between 12 and 24 months. Aboriginal ethnicity (P = 0.01), high Pediatric National Institutes of Health Stroke Scale score (P = 0.001), bilateral infarction (P = 0.001), and large caliber artery territory infarction (P = 0.02) predicted poor outcome. CONCLUSIONS: Our hospital-based incidence and outcome data provide valuable information to help direct treatment strategies and prognosticate children with posterior circulation ischemic stroke. Our study calls for close observation and early management of children with posterior circulation stroke, in particular with aboriginal ancestry and bilateral and large artery territory infarction.

A pediatric institutional acute stroke protocol improves timely access to stroke treatment.

AIM: We aimed to evaluate whether an institutional acute stroke protocol (ASP) could accelerate the diagnosis and secondary treatment of pediatric stroke. METHOD: We initiated an ASP in 2005. We compared 209 children (125 males, 84 females; median age 4.8y, interquartile range [IQR] 1.2-9.3y, range 0.09-17.7y) diagnosed with arterial ischemic stroke 'pre-protocol' (1992-2004) to 112 children (60 males, 52 females; median age 5.8y, IQR 1.0-11.4y, range 0.08-17.7y) diagnosed 'post-protocol' (2005-2012) for time-to-diagnosis, mode of diagnostic imaging, and time-to-treatment with antithrombotic medication (aspirin or anticoagulants). RESULTS: Overall, the interval from symptom onset to diagnosis was similar post-protocol compared to pre-protocol (20.3 vs 22.7h; p=0.109), although mild strokes (Pediatric National Institute of Health Stroke Scale [PedNIHSS] 0-4), were diagnosed faster post-protocol (12.1 vs 36.3h; p=0.003). Magnetic resonance imaging (MRI) was the initial diagnostic modality more often post-protocol (25% vs 1.4%; p<0.001). Initial MRI was more accurate for diagnosing stroke than initial CT (100% vs 47%; p<0.001) with similar time-to-diagnosis. The proportion of children receiving antithrombotic medication within 24 hours doubled in the post-protocol period (83% vs 36%; p<0.001). INTERPRETATION: A pediatric ASP accelerated time-to-treatment, time-to-diagnosis in children with subtle strokes, and increased MRI as initial imaging, reducing the need for computed tomography. Implementing optimized ASPs can facilitate more timely access to diagnosis and management of children with acute stroke.

Longitudinal Outcomes in the 2014 Acute Flaccid Paralysis Cluster in Canada.

We describe the presenting features and long-term outcome of an unusual cluster of pediatric acute flaccid paralysis cases that occurred in Canada during the 2014 enterovirus D68 outbreak. Children (n = 25; median age 7.8 years) presenting to Canadian centers between July 1 and October 31, 2014, and who met diagnostic criteria for acute flaccid paralysis were evaluated retrospectively. The predominant presenting features included prodromal respiratory illness (n = 22), cerebrospinal fluid lymphocytic pleocytosis (n = 18), pain in neck/back (n = 14) and extremities (n = 10), bowel/bladder dysfunction (n = 9), focal central gray matter lesions found in all regions of the spinal cord within the cohort (n = 16), brain stem lesions (n = 8), and bulbar symptoms (n = 5). Enterovirus D68 was detectable in nasopharyngeal specimens (n = 7) but not in cerebrospinal fluid. Acute therapies (corticosteroids, intravenous immunoglobulins, plasmapheresis) were well tolerated with few side effects. Fourteen of 16 patients who were followed beyond 12 months post onset had neurologic deficits but showed ongoing clinical improvement and motor recovery.

Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.

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.