Childhood Arterial Ischemic Stroke Research Articles

Sex Differences in Prognosis of Childhood Arterial Ischemic Stroke: Results From Chinese Pediatric Ischemic Stroke Registry Multicenter Registry

BackgroundCurrent studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. MethodsA retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. ResultsA total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. ConclusionsThis nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.

Immune-Neurovascular Interactions in Experimental Perinatal and Childhood Arterial Ischemic Stroke.

Emerging clinical and preclinical data have demonstrated that the pathophysiology of arterial ischemic stroke in the adult, neonates, and children share similar mechanisms that regulate brain damage but also have distinct molecular signatures and involved cellular pathways due to the maturational stage of the central nervous system and the immune system at the time of the insult. In this review, we discuss similarities and differences identified thus far in rodent models of 2 different diseases-neonatal (perinatal) and childhood arterial ischemic stroke. In particular, we review acquired knowledge of the role of resident and peripheral immune populations in modulating outcomes in models of perinatal and childhood arterial ischemic stroke and the most recent and relevant findings in relation to the immune-neurovascular crosstalk, and how the influence of inflammatory mediators is dependent on specific brain maturation stages. Finally, we discuss the current state of treatments geared toward age-appropriate therapies that signal via the immune-neurovascular interaction and consider sex differences to achieve successful translation.

Abstract 112: Assessing the Impact of the COVID-19 Pandemic on Childhood Arterial Ischemic Stroke: An Unanticipated Natural Experiment

Introduction: The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to confirm prior findings that viral infection can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through VIPS II enrollment, creating an opportunity to assess its impact. Methods: At 22 North American sites, we enrolled 205 children (28 days-18 years) with AIS (12/2016 - 1/2022), collected serum samples up to 7 days post-stroke, and measured clinical infection via parental interview. We defined the COVID-19 pandemic epoch as 1/2020-1/2022. We collected serum samples on 40 stroke-free controls (median [IQR] age 13.2 years [6.4, 16.5]) during the pandemic. We measured SARS-CoV2 spike IgG antibodies (present after vaccination or infection) and nucleocapsid IgG total antibodies (present after infection only; elevated for months). Results: The sites saw 117 AIS cases in 2019 (51 enrolled), 122 (44) in 2020, and 109 (52) in 2021. Comparing the pre-pandemic (N=105) and pandemic (N=100) cohorts, pandemic cases were less likely to report a recent infection (Table). Evidence of SARS-CoV2 infection was seen in 4 (10%) of controls and 26 (25%) of 100 pandemic cases (p=0.065); 10 of the 26 COVID positive cases reported a recent infection, and 7 of the 10 had a clinical diagnosis of COVID. Median (IQR) nucleocapsid IgG titers were 18.8 (12.0, 101) in the positive controls and 50.1 (26.9, 95.3) in the positive cases (p=0.33). Conclusions: The COVID19 pandemic reduced the proportion of childhood AIS cases with preceding infection, likely reflecting decreased infectious exposures while “stay at home” and masking policies were in effect. A quarter of cases in the pandemic era had positive antibodies consistent with prior SARS-CoV2 infection. Like other childhood respiratory viruses, SARS-CoV2 may act as a trigger for childhood AIS, but further investigation is needed to establish a causal role.

Abstract TMP8: Varicella Zoster Virus Infection in Children With Arterial Ischemic Stroke: The Chicken or the Egg?

Introduction: Serologic evidence of varicella zoster virus (VZV) infection has been associated with childhood arterial ischemic stroke (AIS). Questions of causality persist: does VZV infection cause AIS, or does AIS reactivate VZV? The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to examine this relationship. Methods: This North American 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022). Blood samples were hyperacute (≤72hrs; n=194), acute (4-7 days; n=180) and convalescent (1-6 weeks; n=73). A virology research lab used ELISA to measure VZV IgM and IgG titers. A pediatric virologist (CG) interpreted the results and classified the evidence of infection. Low-level IgG seropositivity is consistent with prior vaccination/infection. Highly elevated IgM in hyperacute/acute samples indicated reactivation coincident with stroke . Rising IgG titers between hyperacute and convalescent samples, occasionally with a high IgM in convalescent sample, indicated reactivation after the stroke . Results: Median age (IQR) was 11.6 years (5.3, 15.6). All 205 cases were low-level IgG positive; 160 (78%) reported prior VZV vaccination and 3 reported remote chicken pox. Serologies for 15 (7.3%; 95% CI 4.1, 11.8%) indicated VZV reactivation coincident with stroke; prior VZV vaccination reported in 14 and unknown in one. Stroke etiology amongst these 15 was definite arteriopathy in 4 (27%), possible arteriopathy in 4 (27%), cardioembolic in 5 (33%), and idiopathic in 2 (13%) (compared to 37%, 37%, 10%, 14%, respectively, for the other 190). Among 73 with convalescent samples, 17 (23%) had VZV reactivation after stroke. All cases of VZV reactivation were asymptomatic zoster sine herpete (herpes zoster without rash). Conclusions: While stroke triggered VZV reactivation in 23% of cases, 7.3% had evidence of zoster sine herpete at the time of their stroke, implying a causal role. We could not distinguish antibodies to vaccine virus versus wild-type; these zoster cases could represent reactivation of vaccine virus or a break-through wild-type varicella infection. Either scenario would be unexpected in this current era of routine childhood VZV vaccination and low rates of pediatric chicken pox or zoster.

Three-year incidence and acute setting predictors of epilepsy after neonatal and childhood arterial ischaemic stroke: a disease-based cohort study.

This study identified specific and reliable acute clinical and imaging predictors of PSE in paediatric patients, helping clinicians identify high-risk patients with potential implications for treatment decisions. • Numerous risk factors have been proposed for post-stroke epilepsy, but there is a lack of studies evaluating these variables while accounting for confounding factors and competing risks over time. • After adjustment for competing events, acute symptomatic seizures, both non-status and status epilepticus, abnormal mental status or motor neurological examination at hospital discharge, cortical involvement, and multifocal ischaemic lesions in small strokes are all independent predictors of post-stroke epilepsy. • Knowing the predictors of post-stroke epilepsy is essential for clinicians to make well-informed and effective decisions about treatment.

2 Associations Between Motor Functioning and Intellectual Abilities in Pediatric Arterial Ischemic Stroke

Objective:Motor impairments are one of the most common adverse outcomes after pediatric arterial ischemic stroke (AIS), affecting approximately half of survivors. The development of motor and cognitive skills is closely interrelated, and they share common neural substrates. The objective of this study was to examine whether motor functioning after the acute phase of stroke is associated with school-age intellectual abilities. We also examined associations between concurrent motor functioning and intellectual abilities. Finally, we explored clinical features associated with motor impairments.Participants and Methods:Participants were 64 children, 34 childhood AIS (Meanage= 11.90[2.38]); 30 perinatal AIS (Meanage= 8.75[2.22]), from the Children’s Stroke Program at SickKids Hospital. Motor functioning was assessed with the Pediatric Stroke Outcome Measure sensorimotor subscale at two timepoints, Time 1 or early recovery (childhood group between 30 days post-stroke to 1 year; perinatal group between 2-5 years of age) and Time 2, closest to neuropsychological testing. Intellectual abilities were measured using the Wechsler Intelligence Scale for Children 4th or 5th edition. Associations between motor and intellectual functioning were examined separately in childhood and perinatal AIS groups. Clinical features associated with motor impairment were examined across the full sample.Results:Motor functioning during early recovery was significantly associated with processing speed (r= -.391, p= .036) in the perinatal group and with overall intellectual functioning (r= -.414, p= .018) verbal intellectual abilities (r= -.444, p= .011), working memory (r= .393, p= .026), and processing speed (r= -.351, p= .042) in the childhood group. There were no associations between concurrent motor and intellectual functioning in the perinatal group, and only with processing speed (r= -.525, p= .002) in the childhood group. When motor functioning was dichotomized as no/mild motor deficit and moderate/severe motor deficit at Time 1, children in the perinatal group with moderate/severe motor deficit had significantly lower perceptual reasoning scores (f[28]= 2.15, p= .040) and participants in the childhood group with moderate/severe motor deficit had significantly lower perceptual reasoning (f[32]= 2.35, p= .025) and processing speed (f[32]= 2.14, p= 0.41) scores. There were no differences between no/mild and moderate/severe motor deficit groups for either perinatal or childhood AIS at Time 2. Clinical features associated with moderate/severe motor deficit at Time 1 were cortical+subcortical infarcts, large lesions, presenting with hemiparesis and seizures at time of neuropsychological assessment, and accessing occupational therapy and physical therapy.Conclusions:Results suggest that motor functioning during early stroke recovery is associated with intellectual outcome, whereas motor functioning at time closest to neuropsychological assessment is not. This may be related neuroplastic changes post-injury, likely in frontal-subcortical connections, that result in observable motor deficits after stroke and affect subsequent hierarchal brain maturational processes thereby impacting later cognitive outcome. Different patterns of associations between motor functioning and specific intellectual abilities in perinatal and childhood groups suggest possible age-mediated effects on this relationship.

A quantitative EEG index for the recognition of arterial ischemic stroke in children

ObjectiveTo describe and assess performance of the Correlate Of Injury to the Nervous system (COIN) index, a quantitative electroencephalography (EEG) metric designed to identify areas of cerebral dysfunction concerning for stroke. MethodsCase-control study comparing continuous EEG data from children with acute ischemic stroke to children without stroke, with or without encephalopathy. COIN is calculated continuously and compares EEG power between cerebral hemispheres. Stroke relative infarct volume (RIV) was calculated from quantitative neuroimaging analysis. Significance was determined using a two-sample t-test. Sensitivity, specificity, and accuracy were measured using logistic regression. ResultsAverage COIN values were −34.7 in the stroke cohort compared to −9.5 in controls without encephalopathy (p = 0.003) and −10.5 in controls with encephalopathy (p = 0.006). The optimal COIN cutoff to discriminate stroke from controls was −15 in non-encephalopathic and −18 in encephalopathic controls with >92% accuracy in strokes with RIV > 5%. A COIN cutoff of −20 allowed discrimination between strokes with <5% and >5% RIV (p = 0.027). ConclusionsWe demonstrate that COIN can identify children with acute ischemic stroke. SignificanceCOIN may be a valuable tool for stroke identification in children. Additional studies are needed to determine utility as a monitoring technique for children at risk for stroke.

Acute management of childhood stroke.

The purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures. With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care. There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.

Moyamoya Angiopathy: An Underdiagnosed Cause of Ischemic Stroke in a Tunisian Pediatric Cohort

BackgroundMoyamoya angiopathy is a rare cerebral vasculopathy and an underdiagnosed cause of arterial ischemic stroke in children. We aim to report the clinical and radiological presentations in a Tunisian pediatric cohort. MethodsWe identified moyamoya angiopathy in pediatric patients managed at the Child Neurology Department of Hedi Chaker Sfax University Hospital between 2008 and 2020 and reviewed their clinical and radiological data as well as their evolutionary profile. ResultsWe collected 14 patients with median age 40.6 months and a female predominance (sex ratio of 0.75). An arterial ischemic stroke (AIS) revealed the disease in all patients, with the major symptom being a motor deficit. Symptoms related to a transient ischemic attack before the diagnostic consultation were reported in four patients. Carotid territory was, clinically and radiologically, the most frequently involved. Brain magnetic resonance imaging with angiography was performed in 12 patients confirming the diagnosis by revealing the development of collateral vessels. All the investigations concluded to moyamoya disease in 57.2% and moyamoya syndrome in 42.8%. The latter was related to Down syndrome in five patients and neurofibromatosis type 1 in one patient. With a mean follow-up of 2.35 years, two patients had at least two more AISs during the first two years following diagnosis and 42.8% of patients were diagnosed with vascular or poststroke epilepsy. Full recovery was noted in 14.3% of cases. ConclusionsMoyamoya angiopathy in children is a serious condition that needs to be recognized due to the high risk of recurrent ischemic strokes.

Inherited Thrombophilia Associated With Ischemic Pediatric Stroke in Parent-Child Pairs

BackgroundWe aimed to examine inherited thrombophilia frequencies by extending genetic profile to previously rarely or not investigated polymorphisms in children with ischemic pediatric stroke (IPS) and their parents. MethodsThe study included 33 children: 23 with perinatal arterial ischemic stroke (PAIS), eight with childhood arterial ischemic stroke (CAIS), and two with sinovenous thrombosis and their parents (33 mother-child, 12 father-child, and 12 mother-father-child pairs). Genotyping of FV-Leiden, FV-H1299R, FII-G20210A, β-fibrinogen-455G>A, FXIII-A-Val34Leu, PAI-1(4G/5G), HPA-1, MTHFR-C677T, MTHFR-A1298C, ACE(I/D), and APOE(ε2-4) was performed using CVD Strip assay (ViennaLab, Austria). ResultsAt least one and up to seven simultaneously present polymorphisms were observed in all children with IPS, mothers, and fathers. More than five simultaneously present polymorphisms were identified threefold more frequently in children with IPS (10 of 33; 30%) compared with the child control group (17 of 150; 11%), yielding a statistically significant difference between the two groups (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.39 to 8.35; P = 0.012). Stronger association was revealed for PAIS (OR = 4.17; 95% CI = 1.55 to 11.29; P = 0.008) and CAIS subgroups (OR = 7.82; 95% CI = 1.79 to 34.20; P = 0.012). Complete match of polymorphisms was not identified in any parent-child pair. A partial match (one to four mutual polymorphisms) was found in 11 of 12 parent-child pairs where until three mutual polymorphisms was present in 11 of 12 (91.7%) father-child compared with 21 of 33 (63.6%) mother-child pairs. ConclusionsAccording to obtained results the simultaneous presence of more than five polymorphisms is associated with a higher risk for IPS occurrence, suggesting the risk enhancement for PAIS in the presence of pregnancy complications or for CAIS in conjunction with maternal comorbidity and positive family history. The presence of up to three mutual polymorphisms more frequently in father-child than mother-child pairs suggests significant paternal contribution of inherited thrombophilia to increased risk of IPS.

Thrombophilia screening in the routine clinical care of children with arterial ischemic stroke.

Current guidelines recommend thrombophilia evaluation in childhood arterial ischemic stroke, but the impact of screening on management is unknown. The objective of the current study is to report the incidence of thrombophilia identified as part of routine clinical care in the context of available literature reports, and to describe the impact of a diagnosis of thrombophilia on patient management. We conducted a single-institution retrospective chart review for all children with arterial ischemic stroke occurring between January 1, 2009 and January 1, 2021. We collected thrombophilia screening results, stroke etiology, and management. We also reviewed the literature of thrombophilia testing in childhood arterial ischemic stroke published prior to June 30, 2022. Meta-analysis methods were used to assess prevalence rates. Among children with thrombophilia testing performed, 5% (six of 122 patients) were factor V Leiden heterozygous, 1% (one of 102 patients) were prothrombin gene mutation heterozygous, 1% (one of 122) had protein S deficiency, 20% (23/116 patients) had elevated lipoprotein(a), 3% (three of 110 patients) had elevated homocysteine levels, and 9% (10/112) had elevated antiphospholipid antibodies, only two of whom had persistently elevated levels. There was no change in stroke therapy due to these results. Literature review revealed a wide range of prevalence for most thrombophilia traits, with high cross-study heterogeneity in most cases. The rates of thrombophilia in our cohort were consistent with that expected in the general population. The identification of thrombophilia did not alter stroke care. However, some of the results were actionable, prompting evaluation for lipid disorders and patient-specific counseling on cardiovascular risk and risk for venous thrombosis.

Falsely Reassuring Head CT Delays Diagnosis in Childhood Arterial Ischemic Stroke (P14-9.001)

<h3>Objective:</h3> To describe the impact of non-diagnostic head CT in the evaluation of acute childhood stroke. <h3>Background:</h3> Diagnosis of childhood arterial ischemic stroke is often delayed. Head MRI is recommended to evaluate the stable child with acute neurologic deficit due to the high frequency of stroke mimics. However, head CT is often pursued first as it is easily available and routinely used in adult stroke codes. <h3>Design/Methods:</h3> We performed a retrospective single institution study of children age 1 month to 18 years seen between 2009 and 2021 who were diagnosed with stroke within 72 hours of symptom onset. Patients were identified using diagnostic codes for AIS were reviewed to confirm diagnosis and chart review was used to extract data about clinical presentation and neuroimaging. <h3>Results:</h3> 110 children (mean 9.9 years, 52% male) were diagnosed at a mean of 19.7 (median 14.3) hours. Mean time to diagnosis was 19.7 (median 13.6) hours in 34 patients diagnosed on initial head CT, 19.9 hours (med 15.3) in 50 patients with an initial non-diagnostic head CT followed by diagnostic head MRI, and 19.2 hours (median 13.5) in 26 patients patients diagnosed on head MRI alone. In the 24 patients with a diagnostic CT followed by confirmatory MRI, mean time from CT to MRI was 18.5 (median 12.3) hours. In the 50 patients with non-diagnostic CT followed by diagnostic MRI, the mean time from non-diagnostic CT to diagnostic MRI was 11.9 hours (median 8.1) hours. This difference in medians of 4.2 hours (95%CI: −3.4, 12.2), while not statistically significant, suggests clinically significant ordering patterns with room for improvement. <h3>Conclusions:</h3> Time to MRI following CT was not significantly different between children with and without diagnostic CT, suggesting that that in patients being evaluated for a suspected acute neurologic process, a negative head CT may be falsely reassuring and delay to diagnosis. <b>Disclosure:</b> Dr. Chiang has nothing to disclose. Dr. Barry has nothing to disclose. Dr. Amlie-Lefond has nothing to disclose.

Outcome in Childhood Stroke: Comparing Functional Outcome by Modified Rankin Scale with Neurological Outcome by Pediatric Stroke Outcome Measure

AbstractDifferent scales are used as outcome predictors following arterial ischemic stroke (AIS) in children. Pediatric stroke outcome measure (PSOM) gives information about neurological deficits and function and modified Rankin scale (mRS) about functional outcome. Research examining the relationship between the two measures is scarce. The aim of this study is to correlate the two different scales and to get some information on the long course of outcomes according to these outcome measures. Sixty-one children with the diagnosis of AIS and normal neurodevelopment prior to stroke were investigated. Results of outcome measures (PSOM and mRS) from ≥ 2 years of follow-up were analyzed. Changes of neurological deficits (subcategories of PSOM) over time (discharge, 6 months, and ≥2 years) and prognostic impact on the outcome of the Pediatric National Institutes of Health Stroke Scale and etiology/risk factors are presented.Cramer's V with a coefficient of 0.836 (df-1) indicates a strong association between dichotomized total PSOM and mRS scores. The correlation between the total scales was strong (rho = 0.983, p &lt; 0.001). The correlation coefficient was highest for sensorimotor (rho = 0.949, p &lt; 0.001), then for language (rho = 0.464, p &lt; 0.001) and cognitive (rho = 0.363, p = 0.004) subscales. PSOM scores improved at 6 months compared to the discharge state in sensorimotor (p&lt;0.001) and language (p&lt;0.026) domains, however, there was no statistically significant difference between PSOM scores at 6 months and &gt;2 years follow-up. There was no improvement in cognitive PSOM scores during the follow-up period.There was a high concordance level between the two scales, illustrating that long-term neurological deficits after stroke are related to poor functional outcome. Significant improvement of sensorimotor and language function happened within the period from onset to 6 months of follow-up. Thus, early mobilization of appropriate rehabilitative therapy might improve the outcome. We conclude that both outcome classifications are applicable for assessing outcome after childhood AIS.

Pediatric stroke: a review

Background &amp; Objectives:&#x0D; Pediatric stroke is a focal neurological deficit lasting more than 24 hours because of stenosis, occlusion or rupture of cerebral blood vessels. Variable etiological factors are involved ranging from cardiac, haematological, infectious, immune mediated to arteriopathies which is emerging as most important cause of arterial ischemic stroke in children. In this review article we will discuss paediatric stroke with its epidemiology, etiological factors in particular arteriopathies, diagnostic modalities, management protocols and outcome.&#x0D; Methods: &#x0D; We searched stroke in Pubmed and found 15315 articles, narrowed down to stroke in children (3814) and selected 45 articles for review.&#x0D; Review:&#x0D; Stroke in children is defined as a focal neurological deficit that persists for more than 24 hours and is caused by stenosis, occlusion or rupture of cerebral blood vessels. Stroke may be arterial, venous or because of occlusion of venous sinuses. Arterial strokes may be ischemic, haemorrhagic or ischemic-haemorrhagic.&#x0D; About half of strokes in children are of arterial ischemic strokes in contrast to adults where about 80-85% strokes are of arterial ischemic strokes. Stroke in children is comparable to brain tumors and is one of top ten common causes of death in children.&#x0D; Arterial ischemic stroke in children has significant risk of mortality and morbidity leading to functional disability of patient along with financial burden over family and society. In one study it was estimated that 10-25% of children with stroke die, 25% have recurrence and about 66% of children have neurological deficit after recovery from acute illness or have future epilepsy, behaviour disorder or learning disabilities.&#x0D; Early recognition and prompt treatment of paediatric stroke can reduce mortality, morbidity and in return can reduce both social and financial burden over society.&#x0D; Conclusion:&#x0D; In this review article we will discuss paediatric strokes, epidemiology, risk factors, differential diagnosis, investigations, management protocols, preventive measures and outcome.

Visuospatial processing skills following unilateral arterial ischemic stroke in childhood.

Due to the rare occurrence of childhood stroke, its impact on later cognitive functioning remains unclear. While it is often assumed that children recover better than adults, recent studies suggest that childhood stroke can negatively affect a wide range of cognitive domains, such as attention, language, and processing speed, among others. We examined the effect of unilateral stroke on children's visuoconstructive ability and visual memory. Seventeen children with left- or right-sided arterial ischemic stroke were tested using subtests of the Hamburg-Wechsler Intelligenztest für Kinder and the Rey-Osterrieth Complex Figure(ROCF). The ROCF was evaluated both quantitatively and qualitatively with the help of two separate scoring methods. We found that lesion laterality and age at stroke impacted childhood stroke patients' ability to recall certain elements of the figure. Regarding lesion laterality, left-sided stroke patients had more difficulties recalling internal details than right-sided stroke patients. In terms of age, patients with stroke onset before the age of 5 years remembered fewer structural elements than patients with stroke onset after the age of 5 years did. Moreover, the qualitative scoring method better differentiated between individuals and between groups than the more commonly used quantitative method. The results of this study not only highlight the importance of a qualitative assessment of the ROCF but could also aid clinicians in testing stroke patients more accurately and tailoring subsequent therapy to the patient's individual needs.

Clinical and Imaging Clues of Arteriopathy-Related Pediatric Arterial Ischemic Stroke: A Single Center Experience.

Arteriopathy is a common etiology for childhood arterial ischemic stroke (AIS). In this study, we aimed to address clinical, demographic, and neuroimaging characteristics and the reversibility of vasculopathy in patients with childhood stroke due to arteriopathy by classifying them according to Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria. We included 15 patients with AIS due to arteriopathy presented between 2013 and 2018. All patients were diagnosed and followed up using magnetic resonance imaging (MRI) studies. All acute AIS patients were classified by acute CASCADE criteria (1-4). Moreover, each group was categorized according to the chronic CASCADE criteria, including progressive, stable, reversible, and indeterminate courses. In the study population, CASCADE 2 patients were the most common group, and basal ganglia involvement was the most common involvement in CASCADE 2 patients. Of CASCADE 2 patients, 71.4% received steroids, which was compatible with a favorable outcome. In the study, trauma was present in 33.3% of patients, 60% of which was related to CASCADE 4. In the control visit on month 24, there were neuromotor sequelae of 60%, including hemiparesis, facial paralysis, and decreased fine motor skills; furthermore, the recurrence rate was 20%. We strongly emphasize that arteriopathy should be kept in mind in school-age children presenting with hemiparesis and headache. Moyamoya disease must be considered in the differential diagnosis with anterior circulation involvement, while focal cerebral arteriopathy (FCA) in patients with basal ganglia involvement was detected on MRI and dissection in the patients with a history of head-neck injury. We think that steroids have positive influences on neurologic prognosis in patients with FCA.

[Arterial ischemic stroke in childhood and adolescence : Time-critical emergency in pediatrics].

Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with awide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in amultiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.

Etiological Risk Factors Profile of Arterial Ischemic Stroke in Children at A Tertiary Care Children's Hospital

Objective: To determine the etiological risk factors of arterial ischemic stroke (AIS) in children. Study Design: An observational cohort study. Place and Duration of the Study: Neurology department of “The Children's Hospital and Institute of Child Health, Multan”, from January 2020 to December 2020. Methods: Children in the age group from one month of age to 12 years with a history of acute onset of focal neurological deficit of upper motor nerve and positive findings on neuroimaging were included in the study. The workup included baseline lab testing, neuroimaging, cardiac evaluation, and cerebro-spinal fluid (CSF) laboratory testing. We used predesigned proforma for recording the patient's details and the possible etiology of the stroke. Results: In a total of 84 children, 28 (33.3%) were male and 56 (66.7%) were female. Age ranged from 4 months to 11 years with a mean age of 3.4±2.2 years. Etiological risk factors identified in 62 (73.8%) patients and were remained undetermined in 22 (26.2%) patients. The risk factors identified were central nervous system infection arteriopathy in 22 (26.2%), iron deficiency anemia 20 (23.8%), cardiac disorders 11 (13.1%), moyamoya disease in 5 (6.0%), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes in 4 (4.8%) patients. Practical Implications: It is essential to know the etiology of risk factors responsible for AIS as the management and prognosis are directly influenced by them. Conclusion: Infection-associated arteriopathy was the most common etiological risk factor for arterial ischemic stroke in our study population. Keywords: Anemia, arterial ischemic stroke, central nervous system, moamoya

Why Would a Child Have a Stroke?

Identifying the etiology of childhood arterial ischemic stroke helps prevent stroke recurrence. In addition, stroke may herald a serious underlying condition requiring treatment, such as acquired heart disease, malignancy, or autoimmune disorder. Evidence-based guidelines exist for adults to identify and treat common risk factors for primary and secondary stroke, including hypertension, diabetes, elevated lipids, atrial fibrillation, and sleep apnea, which are rarely relevant in children. However, guidelines do not exist in pediatrics. Identifying the cause of childhood stroke may be straightforward or may require extensive clinical and neuroimaging expertise, serial evaluations, and reassessment based on the evolving clinical picture. Risk factors may be present but not necessarily causative, or not causative until a triggering event such as infection or anemia occurs. Herein, we describe strategies to determine stroke etiology, including challenges and potential pitfalls.

Hemostatic and Thrombotic Considerations in the Diagnosis and Management of Childhood Arterial Ischemic Stroke: A Narrative Review

Although rare in children, arterial ischemic stroke (AIS) is associated with increased mortality and neurological morbidity. The incidence of AIS after the neonatal period is approximately 1-2/100,000/year, with an estimated mortality of 3-7%. A significant proportion of children surviving AIS experience life-long neurological deficits including hemiparesis, epilepsy, and cognitive delays. The low incidence of childhood AIS coupled with atypical clinical-presentation and lack of awareness contribute to delay in diagnosis and consequently, the early initiation of treatment. While randomized-clinical trials have demonstrated the efficacy and safety of reperfusion therapies including thrombolysis and endovascular thrombectomy in appropriately-selected adult patients, similar data for children are unavailable. Consequently, clinical decisions surrounding reperfusion therapy in childhood AIS are either extrapolated from adult data or based on local experience. The etiology of childhood AIS is multifactorial, often occurring in the setting of both acquired and congenital risk-factors including thrombophilia. While multiple studies have investigated the association of thrombophilia with incident childhood AIS, its impact on stroke recurrence and therefore duration and intensity of antithrombotic therapy is less clear. Despite these limitations, a significant progress has been made over the last decade in the management of childhood AIS. This progress can be attributed to international consortiums, and in selected cohorts to federally-funded clinical trials. In this narrative review, the authors have systematically appraised the literature and summarize the hemostatic and thrombotic considerations in the diagnosis and management of childhood AIS focusing on the evidence supporting reperfusion therapies, relevance of thrombophilia testing, and duration and drug choices for secondary-prophylaxis.