Recurrent Arterial Ischemic Stroke Research Articles

The relationship between thrombotic genetics markers and recurrent arterial ischemic stroke in young (S36.007)

<h3>Objective:</h3> This study aims to determine significant clinical and genetic factors of AIS recurrence. <h3>Background:</h3> The involvement of thrombotic genetic markers such methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T and A1298C), factor V Leiden (FVL), G20210A mutation of prothrombin (PT) and recurrent arterial ischemic stroke (AIS) in adults remains unclear. <h3>Design/Methods:</h3> We investigated a cohort study of AIS patients (18–50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried out through a multivariable logistic regression model. <h3>Results:</h3> Two hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional risk factors notably hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. The TT polymorphism of MTHFR 677 increased 2.4-fold the risk of AIS recurrence (OR: 2.47; 95%CI [1.35–4.53]). Both variants AC and CC of MTHFR 1298 polymorphism were associated with a second ischemic cerebral attack (OR:2.68, 95%CI [1.44–4.90], 6.89, 95%CI [2.35–20.23], respectively). The GA variation of FVL was considered a significant genetic factor increasing the risk of AIS recurrence 2.5-fold (OR: 2.54; 95% CI [1.15–5.61]). But, no significant difference was observed between the two groups concerning PT mutation. <h3>Conclusions:</h3> Our findings suggest that besides traditional risk factors, the MTHFR polymorphisms, and FVL play an important role in increasing the risk of recurrent AIS in young patients. <b>Disclosure:</b> Miss M’barek has nothing to disclose. khadija maalla has nothing to disclose. Nadia Bouattour has nothing to disclose. Sawsan Daoud has nothing to disclose. Nouha Farhat has nothing to disclose. mariem damak has nothing to disclose. Salma Sakka has nothing to disclose. Prof. Mhiri has received personal compensation for serving as an employee of Hikma. Prof. Mhiri has received personal compensation for serving as an employee of Sanofi Genzyme. Prof. Mhiri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Prof. Mhiri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche.

Abstract TP168: Quantitative Cerebrovascular Reactivity Atlas In Children

Introduction: Cerebrovascular reactivity (CVR) can be measured by inducing carbon dioxide (CO 2 ) changes in the circulation and measuring subsequent changes in blood flow with functional MRI blood oxygen level dependent sequences (BOLD). In clinical practice, abnormalities in CVR imaging can serve as a biomarker of ischemic risk. To characterize pathological aberrations in CVR, it is essential to have quantitative reference data as to what constitutes normal CVR across brain regions at various stages of development. Methods: Prospective enrollment of healthy children ages 6 to 18. Target N of 40. Two datasets are being generated within the atlas using two different methods of administering the vasoactive stimulus (CO 2 ): a breath-hold CVR dataset (endogenous stimulus) and a RespirAct TM CVR dataset (exogenous). A test of normality is performed on CVR values for each voxel across subjects, with mean and standard deviation calculations. This will allow for generation of a Z-score for each CVR value per voxel in any clinical CVR study. Voxel-wide validation of breath-hold CVR values against the gold standard RespirAct TM CVR values will be performed using within subject t-test and between group comparisons. Subgroup analysis based on gender and age will also be performed. Results: Preliminary CVR data for 8 healthy right-handed children is presented (4 female, median age 13, range 9 -14 years). All participants tolerated CVR studies well and no side effects were reported. Group datasets acquired to date passed tests of normality with no significant differences in CVR values between the two methods found. Conclusions: This study will generate the first atlas of quantitative CVR-fMRI data in healthy children. Normative physiological data on CVR changes throughout childhood, and associations between CVR, blood pressure, age, and gender will be obtained. CVR imaging is performed clinically in patients with a risk of recurrent arterial ischemic stroke such as those with intracranial arteriopathies, sickle cell disease and other genetic and metabolic disorders. Our atlas can provide clinicians with objective measures regarding extent and distribution of CVR abnormalities, allow for stroke risk stratification, and aid in determining the optimal time for intervention.

Arterial ischemic stroke in children with congenital heart diseases.

We describe the prevalence, thromboembolic risk factors, and neurologic outcomes in children with congenital heart disease (CHD) and arterial ischemic stroke (AIS). We retrospectively analyzed the clinical data of children with CHD and AIS from 2000 to 2016. Demographics, procedural and postprocedural data, neuroimaging findings, details of antithrombotic treatment, and neurological status at last follow up were evaluated. Patients with cyanotic CHD accounted for 24 of 30 cases with AIS. The majority of AIS (70%) was procedure related, and the mean time from procedure to diagnosis of stroke was 9.7 (range, 1-30) days. At the time of AIS, 14 (46.7%) patients revealed coexistence of additional thromboembolic causes of AIS. Three patients (10.0%) experienced recurrent AIS and six patients (20.0%) were diagnosed with post-stroke epilepsy. The unfavorable outcomes were found in 13 patients (43.3%), including four deaths. The unfavorable outcome was significantly associated with the main branch involvement of middle cerebral artery (OR = 10.296, 95% CI = 1.335-79.439) and hemorrhagic transformation (OR = 16.264, 95% CI = 1.359-194.690). Additional thromboembolic risk factors such as systemic or cardiac thrombus, arrhythmia, and surgical procedures for cyanotic CHD were found in patients with CHD and AIS. The main branch involvement of middle cerebral artery and hemorrhagic transformation were significant predictors of unfavorable outcomes. Further studies are required to identify the target for stroke prevention and develop better prophylactic strategies to minimize AIS in patients with CHD.

Traditional risk factors and combined genetic markers of recurrent ischemic stroke in adults

BackgroundThe involvement of traditional risk factors and combined genetic markers of recurrent arterial ischemic stroke (AIS) in adults remains unclear. ObjectiveThis study aims to determine significant clinical and genetic factors of AIS recurrence, and to investigate the combined effect of genotypes on the occurrence of a second cerebral ischemic attack. MethodsWe investigated a cohort study of AIS patients (18–50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried through a multivariable logistic regression model. We used a Cox proportional hazard model for identifying predictors of recurrence. ResultsTwo hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional and genetic risk factors such as hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. This risk increased with increasing number of genetic factors. The hazard ratio (HR) was 0.66 (95% confidence interval [CI] 0.97–2.67) for the subject with one genetic factor, 1.61 (95% CI 0.97–2.25) for combined methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and 2.57 (95% CI 1.32–4.99) for combined factor V Leiden (FVL) and MTHFR polymorphisms (677 or 1298). The HR for the three polymorphisms combined was 6.04 (95% CI 2.40–15.16). ConclusionsOur findings suggest that cumulative effect of both traditional and common genetic risk factors was associated with recurrence of ischemic stroke. We demonstrated for the first time that a combined genotype FVL/MTHFR profile increase the risk of a second cerebral ischemic attack.

Expanding the clinical and neuroimaging features of post-varicella arteriopathy of childhood.

Post-varicella arterial ischemic stroke (AIS) is considered an uncommon cause of pediatric stroke that is considered a self-limiting, monophasic disease. However, in a subset of patients, disease recurs; the prevalence of vasculopathy or AIS recurrence, severity of clinical outcomes, and standardized therapies have not been well characterized. Herein, we determined the clinical-neuroradiological features, long-term evolution, and relationship between acute phase treatment and vasculopathy recurrence in a pediatric population with post-varicella AIS. Clinical, laboratory, and neuroradiological features of 22 children with post-varicella AIS between 2010 and 2019 (16 males, mean age at stroke 4 years, range 1.7-10) were reviewed. Statistical analyses were performed using χ2 and Fisher exact tests. Of the 22 cases, mean time from varicella to stroke was 4.5 months with 3 cases presenting more than 12 months after rash; 21 (95%) were not vaccinated for varicella; 3 (13.6%) had posterior circulation involvement; and 5 (22.7%) had AIS or vasculopathy recurrence, of which 4 recurred 6.1 months to 2.8 years after initial clinical onset. Recurrence was associated with lack of antiviral treatment during the first episode (p = 0.02). Post-varicella AIS can occur months after rash making diagnosis challenging. Because recurrent vasculopathy was seen predominantly in cases not treated with antiviral therapy during initial presentation, it is important to rapidly diagnose post-varicella AIS through clinical criteria and/or virological testing then treat with antivirals to prevent recurrence.

Rivaroxaban in Recurrent Ischemic Stroke Due to Protein S Deficiency: A Case Report.

Protein S deficiency is a thrombophilia associated with an increased risk of thromboembolism. Previous studies have shown its role as a predisposing factor for venous thromboembolism, but its role in recurrent arterial ischemic stroke remains uncertain. Here we report a patient with recurrent ischemic stroke due to protein S deficiency. Oral anticoagulant treatment with vitamin K antagonist (VKA) drugs is used to treat and prevent thromboembolic events caused by thrombophilia, but it has many limitations, especially in the case of recurrent thromboembolic events. Direct oral anticoagulants (DOACs) have many advantages over VKA. Previous studies have shown that they are safe in cases of thrombophilia, but they are not well studied in recurrent ischemic stroke due to protein S deficiency. In this study our patient was treated with rivaroxaban. Protein S deficiency may be a predisposing factor in recurrent ischemic stroke, and rivaroxaban can be a safe and effective treatment option. Further studies are needed to confirm our findings.

Cancer and Tumor-Associated Childhood Stroke: Results From the International Pediatric Stroke Study

BackgroundThe prevalence of cancer among children with stroke is unknown. This study sought to evaluate cancer- and tumor-associated childhood ischemic stroke in a multinational pediatric stroke registry. MethodsChildren aged 29 days to less than 19 years with arterial ischemic stroke or cerebral sinovenous thrombosis enrolled in the International Pediatric Stroke Study between January 2003 and June 2019 were included. Data including stroke treatment and recurrence were compared between subjects with and without cancer using Wilcoxon rank sum and chi-square tests. ResultsCancer or tumor was present in 99 of 2968 children (3.3%) with arterial ischemic stroke and 64 of 596 children (10.7%) with cerebral sinovenous thrombosis. Among children in whom cancer type was identified, 42 of 88 arterial ischemic stroke cases (48%) had brain tumors and 35 (40%) had hematologic malignancies; 45 of 58 cerebral sinovenous thrombosis cases (78%) had hematologic malignancies and eight (14%) had brain tumors. Of 54 cancer-associated arterial ischemic stroke cases with a known cause, 34 (63%) were due to arteriopathy and nine (17%) were due to cardioembolism. Of 46 cancer-associated cerebral sinovenous thrombosis cases with a known cause, 41 (89%) were related to chemotherapy-induced or other prothrombotic states. Children with cancer were less likely than children without cancer to receive antithrombotic therapy for arterial ischemic stroke (58% vs 80%, P = 0.007) and anticoagulation for cerebral sinovenous thrombosis (71% vs 87%, P = 0.046). Recurrent arterial ischemic stroke (5% vs 2%, P = 0.04) and cerebral sinovenous thrombosis (5% vs 1%, P = 0.006) were more common among children with cancer. ConclusionsCancer is an important risk factor for incident and recurrent childhood stroke. Stroke prevention strategies for children with cancer are needed.

Risk Factors for Recurrent Arterial Ischemic Stroke in Children and Young Adults.

Arterial ischemic stroke (AIS) experienced at a young age is undoubtedly a serious medical problem. AIS very rarely occurs at a developmental age, whereas in young adults, it occurs with a higher frequency. The etiologic mechanisms of AIS occurring in childhood and adulthood differ. However, for both age populations, neurological consequences of AIS, including post-stroke seizures, motor disability, and recurrence of the disease, are connected to many years of care, rehabilitation, and treatment. Recurrent stroke was observed to increase the risk of patients’ mortality. One of the confirmed risk factors for recurrent stroke in children is the presence of vasculopathies, especially Moyamoya disease and syndrome, and focal cerebral arteriopathy of childhood (FCA). FCA causes a 5-fold increase in the risk of recurrent stroke in comparison with idiopathic AIS. In turn, young adults with recurrent stroke were found to more often suffer from hypertension, diabetes mellitus, or peripheral artery disease than young patients with first-ever stroke. Some reports also indicate relationships between specific genetic polymorphisms and AIS recurrence in both age groups. The aim of the present literature review was to discuss available data regarding the risk factors for recurrent AIS in children and young adults.

Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population

OBJECTIVE:Risk factors for arterial ischemic stroke (AIS) in children are multiple and include cardiac disease, vasculopathy, and prothrombotic risk factors (PR). The relevance of these factors to a second AIS event is incompletely understood.METHODS:We conducted a multicenter cohort study to assess the rate of symptomatic stroke recurrence following initial AIS, pooling data on recurrent AIS from the databases held in Canada, Germany, and UK. We followed 894 patients aged 1 month to 18 years (median 6 years) at initial AIS for median 35 months.RESULTS:160 of 894 patients (17.9%) had recurrence from 1 day to 136 months (median 3.1 months) after first AIS. Recurrence was significantly more common in children with (hazard ratio (HR) 2.5, 95% confidence intervals (CI) 1.92-3.5, p<0.001) compared to children without vasculopathy. After adjusting for vasculopathy, antithrombin deficiency, elevated lipoprotein (a), and the presence of any combined PR were independently associated with recurrence. Recurrence rates calculated per 100 person-years were 10 (95%CI: 3-24) for antithrombin deficiency, 6 (95%CI 4-9) for elevated Lp(a), and 13 (95%CI 7-20) for combined PR.CONCLUSIONS:Identifying children at increased for recurrent AIS events is important in intensifying preventative measures. Among 894 Canadian, English and German pediatric stroke patients, 17.9% experienced recurrent AIS at a median of 3.1 months after the index stroke. The presence of more than one prothrombotic risk factor is associated with AIS recurrence in children DisclosuresNo relevant conflicts of interest to declare.

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.

Rates and Risk Factors for Arterial Ischemic Stroke Recurrence in Children.

Recurrent ischemic events are common in children with arterial ischemic stroke (AIS) and put patients at risk for further neurological impairment. This study sought to identify rates and risk factors for recurrent AIS or transient ischemic attack in a cohort of children seen after index AIS and uniformly investigated and managed using contemporary clinical guidelines. Case note and radiology review of children >28 days and <18 years of age who presented to Great Ormond Street Hospital from 2005 to 2015 with index AIS. Demographic characteristics, medical history, index AIS features, radiological findings, and neurological outcome were examined. Recurrence was identified from clinical records and coded as AIS (if there was associated new cerebral infarction) or transient ischemic attack. Eighty-four children (43 girls; median age at index AIS, 4.1 years) were identified. Cumulative AIS recurrence was 5% at 1 month, 10% at 3 months, 12% at 6 months, 12% at 12 months, and 15% at 60 months after index event. Factors that independently predicted AIS recurrence were referral to Great Ormond Street Hospital from outside the catchment area, a prior relevant diagnosis, bilateral arteriopathy, and AIS CASCADE category 3A or 3B (Childhood AIS Standardized Classification and Diagnostic Evaluation). Multiple infarcts and evidence of mature, as well as acute, infarcts on first brain imaging, although independently associated with AIS recurrence, were also associated with bilateral arteriopathy. Only CASCADE categories 3A and 3B (bilateral cerebral arteriopathy with or without collaterals) remained significant in multivariate analysis. AIS recurrence was not associated with poor neurological outcome. AIS recurrence remains a significant problem, despite the wide use of antithrombotic medications. AIS subtypes should direct clinicians and future trials to use stratified management strategies and durations of treatment. Bilateral cerebral arteriopathies are especially sinister, and consensus criteria should be developed to improve consistency of management.

Clinical features, course, and outcomes of a UK cohort of pediatric moyamoya.

To describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors. Retrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome. Eighty-eight children (median presentation age 5.1 years) were included. Thirty-six presented with arterial ischemic stroke (AIS) and 29 with TIA. Eighty had bilateral and 8 unilateral carotid circulation disease; 29 patients had posterior circulation involvement. Acute infarction was present in 36/176 hemispheres and chronic infarction in 86/176 hemispheres at the index presentation. Sixty-two of 82 with symptomatic presentation had at least one clinical recurrence. Fifty-five patients were treated surgically, with 37 experiencing fewer recurrences after surgery. Outcome was categorized as good using the Recovery and Recurrence Questionnaire in 39/85 patients. On multivariable analysis, presentation with TIA (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02-0.35), headache (OR 0.10, 95% CI 0.02-0.58), or no symptoms (OR 0.08, 95% CI 0.01-0.68) was less likely to predict poor outcome than AIS presentation. Posterior circulation involvement predicted poor outcome (OR 4.22, 95% CI 1.23-15.53). Surgical revascularization was not a significant predictor of outcome. Moyamoya is associated with multiple recurrences, progressive arteriopathy, and poor outcome in half of patients, especially with AIS presentation and posterior circulation involvement. Recurrent AIS is rare after surgery. Surgery was not a determinant of overall outcome, likely reflecting surgical case selection and presentation clinical status.

Recurrent arterial ischemic stroke with good response to mycophenolate mofetil

Recurrent arterial ischemic stroke with good response to mycophenolate mofetil

Abstract 170: Role of Patent Foramen Ovale in First and Recurrent Childhood Cryptogenic Arterial Ischemic Stroke

Background: Numerous studies in adults have reported a robust association between patent foramen ovale (PFO) and cryptogenic arterial ischemic stroke (AIS), particularly in younger adults. The association between PFO and stroke in children has not been well characterized and the clinical significance of identifying a PFO in a child with first or recurrent cryptogenic stroke is currently unknown. Methods: We performed a retrospective case control analysis of a 10-year prospectively enrolled cohort of children with acute AIS who underwent transthoracic echocardiogram (TTE) as part of their diagnostic evaluation. We compared PFO prevalence in children with cryptogenic stroke to those with known stroke etiologies and to non-stroke controls. We also assessed stroke recurrence risk in children with vs without PFO and assessed PFO features that may confer higher stroke risk. Results: Of 119 children with first-ever AIS, 59 had TTE available for central review, of which 17 were cryptogenic and 42 had a known cause. PFO prevalence was higher in the cryptogenic stroke group (X, 24%) compared to both the known stroke etiology group (Y, 6%, p = 0.05) and non-stroke controls (Z, 8%, p = 0.05). However, 2 year recurrence free survival rates in stroke patients with PFO did not differ from those without PFO (HR 1.58, 95% CI 0.18-13.62, p = 0.68). PFOs in children with AIS vs controls had numerically more right-to-left shunt at rest (7 vs 0) and atrial septal aneurysm (4 vs 0) but the study was underpowered to look at these factors. Conclusions: In our prospectively enrolled cohort of children with AIS, we found the prevalence of PFO to be higher in children with cryptogenic stroke compared to healthy controls and non-cryptogenic stroke patients. The implication of PFO for risk of recurrence and optimal secondary preventative treatment remains uncertain and require further study.

Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry

BackgroundPediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth to 28 days) and older children (29 days to 18 years). MethodsWe conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry, across all 16 Canadian acute care children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 to December 2001 and documented disease incidence, presentations, risk factors, and treatments. Study outcomes were assessed throughout 2008, including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack. ResultsAmong 1129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). The predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac disorders (28%), and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (P < 0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall, an initially decreased level of consciousness, a nonspecific systemic presentation, and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, nonspecific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, nonspecific systemic presentation, risk factors, and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease. ConclusionsThis national data set provides a population-based disease incidence rate and demonstrates the protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke.

The Prevalence of Celiac Disease in Children With Arterial Ischemic Stroke.

The association between arterial ischemic stroke (AIS) and celiac disease (CD) has been described in only a few cases in adults and children. We aim to determine the prevalence of CD in children and adolescents with AIS. We investigated serum levels of tissue transglutaminase antibody immunoglobulin (Ig)A and total IgA from 76 children with AIS and in a healthy control group of 102 children. Study participants who were positive for tissue transglutaminase IgA antibodies underwent a duodenal biopsy. A total of 2 patients in the AIS group (2.26%) and 2 in the control group (1.96%) had positive serum tissue transglutaminase antibody (P=0.89; 95% confidence interval, -5.05 to 6.89). Duodenal biopsy confirmed CD in only 1 patient who had AIS. In the present study, children with acute arterial stroke did not exhibit a higher prevalence rate of CD compared with healthy controls. Therefore, the screening test for CD is not a necessary part of the management of AIS in children. However, cases of recurrent AIS could be examined for CD.

Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke

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

Outcome and recurrence 1 year after pediatric arterial ischemic stroke in a population-based cohort.

Arterial ischemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population-based cohort. Children aged 29 days to < 16 years with radiologically confirmed AIS occurring over a 1-year period residing in southern England (population = 5.99 million children) were eligible for inclusion. Outcome was assessed during a home visit using the Pediatric Stroke Outcome Measure (PSOM). Parental impressions of recovery were assessed using the Pediatric Stroke Recurrence and Recovery Questionnaire. PSOM score was estimated via telephone interview or clinician interview whenever home visit was not possible. Ninety-six children with AIS were identified. Two children were lost to follow-up. Nine of 94 (10%) children died before the 12-month follow-up. One child had an AIS recurrence. PSOM scores were available for 78 of 85 living children at follow-up. Thirty-nine of 78 (50%) had a good outcome (total PSOM score < 1), and 39 of 78 (50%) had a poor outcome. Seizures at onset of AIS were associated with a poor outcome (odds ratio = 3.5, 95% confidence interval = 1.16-10.6). Twenty-eight of 73 (38%) children were judged by their carers to have fully recovered. Ten of 84 (12%) children had recurrent seizures, and 17 of 84 (20%) reported recurrent headaches. AIS carries a significant risk of mortality and long-term neurological deficit. However, the rates of mortality, recurrence, and neurological impairment were markedly lower in this study than previously published figures in the United Kingdom. Ann Neurol 2016;79:784-793.

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

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. 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. 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. 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.

Early-onset bilateral cerebral arteriopathies: Cohort study of phenotype and disease course.

To describe characteristics of young children with arterial ischemic stroke (AIS) and bilateral cerebral arteriopathies. Retrospective review of clinical features, course, and outcome. Neuroimaging was analyzed for infarct pattern, cerebrovascular diagnosis (anatomic/Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation [CASCADE] criteria), and disease progression. In the 31 children (median age, 18 months), presentations included acute hemiparesis (n=23) and focal seizures (n=12). Seven had systemic arterial disease; 13 had cardiac abnormalities. Twenty had recurrent AIS or transient ischemic attack (after median of 3 months); 16 had >1 recurrence. Median modified Rankin Scale score was 3, with motor impairments in 20, cognitive impairments in 11, and seizures in 7. At presentation, 17 had old and acute infarcts. Twenty-five had high signal in white matter. A total of 13/23 reimaged patients accrued further infarcts over a median of 39 months. Arteriopathy involved the carotid circulation bilaterally in all; 6 had posterior circulation and 11 had extracranial involvement. Arteriopathy distribution was symmetric in 24/31. CASCADE categories were 3A in 19, 3B in 5, 3C in 5, and 7 in 2. After a median of 35 months, 14 had had progression of arteriopathy. Patients categorized as CASCADE 3A (moyamoya) had significantly shorter time to recurrence than other groups. Young children with bilateral cerebral arteriopathies (particularly meeting criteria for CASCADE 3A) have a malignant course, with frequent recurrent events, progressive disease, and poor outcomes. Current classifications are limited in characterizing disease in many cases. Symmetric involvement suggests these arteriopathies may be developmentally determined, while systemic involvement suggests potential genetic etiology.