Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Risk factors associated with in-hospital complications for pediatric sickle-cell disease-associated moyamoya syndrome: a nationwide cross-sectional study.

PURPOSE: Sickle-cell disease-associated moyamoya syndrome (SCD-MMS) carries a high risk for recurrent strokes and cerebrovascular morbidity in children. However, few data are available about complications that occur in children hospitalized with SCD-MMS. The purpose of this analysis was to determine the risk factors for in-hospital complications in pediatric SCD-MMS admissions, and thus aid physicians in optimizing future treatment plans. METHODS: A national database of pediatric hospital admissions was examined across the years 2003-2019. ICD-9 and ICD-10 diagnosis codes were analyzed to identify discharges with a primary diagnosis of SCD-MMS and identify in-hospital complications, defined as complication-associated diagnostic codes logged during the same admission. Patient demographics, comorbidities, and hospital characteristics were examined using univariate and multivariate logistic regression analyses to determine associations with in-hospital complications. RESULTS: In total, 274 admissions with a primary diagnosis of SCD-MMS were identified. During 64 (23.4%) admissions, transfusion therapy was given, and in 86 admissions (31.4%), surgical revascularization was performed. In 10 admissions (3.6%), a total of 11 in-hospital complications were identified. After multivariate regression, both comorbid chronic lung disease (adjusted OR 5.3 [1.1, 26.9], P = 0.04) and surgical revascularization (adjusted OR 10.2 [2.0, 52.4], P = 0.006) were associated with development of complications. CONCLUSIONS: In this nationwide database of pediatric SCD-MMS hospitalizations, comorbid chronic lung disease and surgical revascularization were associated with development of in-hospital complications. Patients with comorbid chronic lung disease or who are admitted for revascularization may warrant closer monitoring and greater medical optimization during the hospitalization.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Peer-mentorship and first-year inclusion: building belonging in higher education.

BACKGROUND: An inclusive academic environment is pivotal to ensure student well-being and a strong sense of belonging and authenticity. Specific attention for an inclusive learning environment is particularly important during a student's transition to higher education. At Utrecht University's Medical School, explorative interviews with students from minority groups indicated they did not always feel included during the orientation programme of their academic education. We, therefore, developed a bias awareness training with theoretical and practical components on diversity and inclusion for peer-mentors who are assigned to each first-year student at the start of university. METHODS: At the end of the orientation programme, we investigated the effectiveness of the training for two consecutive years using two measurements. Firstly, we investigated the behavioural changes in the peer-mentors through a (self-reporting) questionnaire. Additionally, we measured the perceived inclusion of the first-year students, divided into belonging and authenticity, using a validated questionnaire. RESULTS: Our results show that peer-mentors found the training useful and indicated it enabled them to create an inclusive atmosphere. Overall, students experienced a high level of inclusion during the orientation programme. After the first year, the bias training was adjusted based on the evaluations. This had a positive effect, as mentors felt they were significantly more able to provide an inclusive orientation in the second year of this study. In line with this, students experienced an increased level of authenticity specifically due to the peer-mentor in the second year as compared to the first. CONCLUSIONS: We conclude that training peer-mentors is an effective way to increase awareness and to ensure an inclusive atmosphere during the start of higher education.

Hemorrhagic Stroke in Children and Adults With Sickle Cell Anemia: The Post-STOP Cohort.

BACKGROUND: Hemorrhagic stroke in young patients with sickle cell anemia remains poorly characterized. METHODS: The Post-STOP (Stroke Prevention Trial in Sickle Cell Anemia) retrospective study collected follow-up data on STOP and STOP II clinical trial cohorts. From January 2012 to May 2014, a team of analysts abstracted data from medical records of prior participants (all with sickle cell anemia). Two vascular neurologists reviewed data to confirm hemorrhagic strokes defined as spontaneous intracerebral, subarachnoid, or intraventricular hemorrhage. Incidence rates were calculated using survival analysis techniques Results: Follow-up data were collected from 2850 of 3835 STOP or STOP II participants. Patients (51% male) were a median of 19.1 (interquartile range, 16.6-22.6) years old at the time of last known status. The overall hemorrhagic stroke incidence rate was 63 per 100 000 person-years (95% CI, 45-87). Stratified by age, the incidence rate per 100 000 person-years was 50 (95% CI, 34-75) for children and 134 (95% CI, 74-243) for adults >18 years. Vascular abnormalities (moyamoya arteriopathy, aneurysm or cavernous malformation) were identified in 18 of 35 patients with hemorrhagic stroke. CONCLUSIONS: The incidence rate of hemorrhagic stroke in patients with sickle cell anemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common etiologies for hemorrhage and screening may be warranted.

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.

Referrals, etiology, prevalence, symptoms, and treatments of chronic cough: A survey of allergy specialists.

BACKGROUND: Chronic cough (CC) affects 11% of the US adult population, and these patients experience persistent symptoms despite adherence to recommended treatment protocols. Further research is needed to identify effective therapies to treat CC. OBJECTIVE: To describe the referral sources, etiology, prevalence, symptoms, and treatments for patients diagnosed with having CC who present to allergy specialists (AS). METHODS: An online survey was administered to 177 AS. The survey queried each AS experience with patients with CC, including the prevalence of CC, source of referrals for patients with CC, and perceived efficacy of treatments. RESULTS: A total of 103 (58%) AS reported that the patients with CC they treated were primarily of female sex (58.26%) and White (65.69%). Family physicians, nurse practitioners, physician assistants, and primary care internists were the most common source of referrals of patients with CC to AS. Furthermore, 20% of the respondents reported a complete resolution of the symptoms for more than 75% of their patients with CC. The top 4 "very common complaints" reported by the patients with CC were social embarrassment, loss of sleep, decreased quality of life, and sleep disruption. The top 4 most frequent treatments prescribed for CC were antireflux treatments, inhaled corticosteroids alone or in combination with long-acting ß-agonist, short-acting bronchodilators, and first-generation antihistamines. None of the therapies were rated "very effective" in greater than 50% of the patients with CC. CONCLUSION: The available treatments for CC do not effectively resolve the symptoms of this condition, and additional treatments need to be developed.

Associations Between Peer Use, Costs and Benefits, Self-Efficacy, and Adolescent E-cigarette Use.

OBJECTIVE: Prior research identified peer use as a salient risk factor of adolescent electronic cigarette (e-cigarette) use, but has not expanded on the mechanisms of this association. METHODS: Participants were 562 adolescents recruited from rural and suburban public high schools and an adolescent medicine clinic in the mid-Atlantic United States. Participants completed a packet of questionnaires that assessed demographics, substance use, expectations about the consequences of e-cigarette use, and perceptions of their own self-efficacy to resist using e-cigarettes. We estimated a series of mediation models using the MODEL INDIRECT command in MPLUS statistical software. In all models, significance of indirect effects from peer e-cigarette use to self-reported e-cigarette use were tested via two variables: (a) expected costs, (b) benefits of e-cigarette use, and (c) the perceived self-efficacy of the individual to refrain from e-cigarette use. RESULTS: Adolescents with more peers using e-cigarettes were more likely to have ever used an e-cigarette and perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 1). Those with more peers using e-cigarettes were more likely to be currently using e-cigarettes themselves because they perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 2). CONCLUSION: Peer use, self-efficacy to resist use, and expectations of cost and benefits of e-cigarette use should be considered as possible targets when devising tailored interventions and policies to prevent or reduce negative health consequences of long-term e-cigarette use.

Pediatric moyamoya MRI score: an imaging-based scale to predict outcomes in surgically treated pediatric patients with moyamoya.

OBJECTIVE: Moyamoya is a progressive arteriopathy that predisposes patients to stroke due to stenosis of the intracranial internal carotid arteries and their proximal branches. Despite the morbidity caused by this condition, the ability to accurately predict prognosis for individual patients remains challenging. The goal of this study was to develop a systematic scoring method based on parenchymal findings on preoperative brain MRI to predict long-term outcomes for surgically treated pediatric patients with moyamoya. METHODS: A retrospective surgical cohort of pediatric patients (≤ 18 years of age at the time of the initial surgery) with moyamoya from a single center were studied. Radiological variables with existing correlations between outcomes in moyamoya or other vascular diseases were chosen to score preoperative MRI based on easily defined parenchymal findings that could be rapidly assessed and used to make a numeric score. Calculated scores were correlated with clinical outcome measures using the Pearson correlation coefficient and area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 35 children with moyamoya disease or moyamoya syndrome were included in the study, with a median follow-up time of 2.6 years from the time of surgery. The pediatric moyamoya MRI score (PMMS) consists of ischemic changes (0-2; 0 = none, 1 = focal, 2 = diffuse), encephalomalacia (0-2; 0 = none, 1 = focal, 2 = diffuse), and hemorrhage (0-1; 0 = not present, 1 = present). PMMSs were highly correlated with pediatric modified Rankin Scale scores at the last follow-up (r = 0.7, 95% CI 0.44-0.84; p < 0.001) as a six-point scale, and when dichotomized (AUROC = 0.85). CONCLUSIONS: The PMMS was found to be a simple tool based on preoperative MRI data that could be quickly and easily calculated and correlated with disability. This scoring method may aid future development of predictive models of outcomes for children with moyamoya disease and moyamoya syndrome.

Multiple Tumor-Associated Intracranial Aneurysms Adjacent to a Suprasellar Germ Cell Tumor: Case Report and Review of Literature.

INTRODUCTION: Tumor-associated intracranial aneurysms are rare and not well understood. CASE PRESENTATION: We describe a 4-year-old female with multiple intracranial aneurysms intimately associated with a suprasellar germ cell tumor (GCT). We provide the clinical history, medical, and surgical treatment course, as well as a comprehensive and concise synthesis of the literature on tumor-associated aneurysms. DISCUSSION: We discuss mechanisms for aneurysm formation with relevance to the current case, including cellular and paracrine signaling pertinent to suprasellar GCTs and possible molecular pathways involved. We review the complex multidisciplinary treatment required for complex tumor and cerebrovascular interactions.

Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture.

BACKGROUND AND PURPOSE: Do children have an increased risk for brain arteriovenous malformation (AVM) recurrence compared with adults and does this risk vary depending on initial presentation with AVM rupture? METHODS: We retrospectively studied 115 patients initially presenting with brain AVM under age 25 years who underwent complete surgical resection of the AVM as documented by digital subtraction angiography (DSA) and had delayed follow-up DSA to evaluate for AVM recurrence after apparent initial cure. RESULTS: The mean time from baseline DSA to follow-up DSA was 2.3 years, ranging from 0 to 15 years. Twelve patients (10.4% of the 115 patient cohort and 16.7% of 72 patients with hemorrhage at initial presentation) demonstrated AVM recurrence on follow-up DSA. All patients with recurrence initially presented with intracranial hemorrhage, and intracranial hemorrhage was a significant predictor of recurrence (log rank P=0.037). Among patients with initial hemorrhage, the 5-year recurrence rate was 17.8% (95% CI, 8.3%-35.7%). All recurrences occurred in patients who were children at the time of their initial presentation; the oldest was 15 years of age at the time of initial AVM surgery. The 5-year recurrence rate for children (0-18 years of age) with an initial presentation of hemorrhage was 21.4% (95% CI, 10.1%-41.9%). Using Cox regression, we found the risk of AVM recurrence decreased by 14% per each year increase in age at the time of initial surgical resection (hazard ratio=0.86 [95% CI, 0.75-0.99]; P=0.031). CONCLUSIONS: There is a high rate of recurrence of apparently cured brain AVMs in children who initially present with AVM rupture. Imaging follow-up is warranted to prevent re-rupture.

Validation of the pediatric stroke outcome measure for classifying overall neurological deficit.

BACKGROUND: The pediatric stroke outcome measure (PSOM) is a standardized, disease-specific outcome measure. We aimed to validate the overall classification of neurological deficit severity using PSOM. METHODS: We identified 367 neonates/children with arterial ischemic stroke (AIS) (Derivation Cohort). We analyzed the PSOM subscales (scored as 0 [no deficit], 0.5 [minimal/mild deficit; normal function], 1 [moderate deficit; slowing function], or 2 [severe deficit; missing function]) to derive severity levels using latent class analysis (LCA). We validated a severity classification scheme (PSOM-SCS) in: (a) children who had Pediatric Evaluation of Disability Inventory (PEDI; n = 63) and/or the Pediatric Quality-of-Life Inventory (PedsQL; n = 97) scored; and (b) an external cohort (AIS; n = 102) with concurrently scored modified Rankin Scale (mRS), King's Outcome Scale for Childhood Head-Injury (KOSCHI) and PSOM. RESULTS: Within the Derivation Cohort, LCA identified three severity levels: "normal/mild," "moderate," and "severe" (83.7%, 13.3%, and 3%, respectively). We developed severity classification based on PSOM subscale scores: "normal/mild"-normal function in all domains or slowing in one domain, "moderate"-slowing in ≥2 domains or missing function in one domain, and "severe"-missing function in ≥2 domains or slowing in ≥1 plus missing in one domain. PEDI and PedsQL both differed significantly across the severity groups. PSOM-SCS displayed high concordance with mRS (agreement coefficient [AC2] = 0.88) and KOSCHI (AC2 = 0.79). CONCLUSION: The PSOM-SCS constitutes a valid tool for classifying overall neurological severity emphasizing function and encompassing the full range of severity in pediatric stroke. IMPACT: Arithmetic summing of the PSOM subscales scores to assess severity classification is inadequate.The prior severity classification using PSOM overestimates poor outcomes.Three distinct severity profiles using PSOM subscales are identified.The PSOM-SCS is in moderate to excellent agreement with other disability measures.PSOM-SCS offers a valid tool for classifying the overall neurological deficit severity.

Review on the Diagnosis and Treatment of Reversible Cerebral Vasoconstriction Syndrome in Children and Adolescents.

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiologic diagnosis that affects children and adolescents, but it is much more frequently reported in adults. Clinically, patients present with severe and commonly recurrent thunderclap headaches. Typical precipitating triggers include vasoactive substances, serotonergic agents, and the postpartum period. There may be associated neurologic complications at presentation or in the weeks following, such as convexity subarachnoid hemorrhage, stroke, cerebral edema, cervical artery dissection (CeAD), and seizures. Angiographically, the cerebral arteries demonstrate segmental vasoconstriction and dilation, although imaging early in the clinical course may be normal. Work-up is performed to exclude intracranial disorders such as vasculitis, subarachnoid hemorrhage due to ruptured aneurysm, meningitis, and intracranial venous sinus thrombosis. Within 1 month of initial symptom onset, clinical symptoms such as severe headache have ceased, and within 3 months, the cerebral vasoconstriction is much improved or resolved. Management involves avoidance of precipitating triggers and potentially short-term pharmacotherapy with calcium channel blockers for patients with associated neurologic complications. Steroids are not recommended and may worsen the clinical outcome. Prognosis is excellent in the large majority of patients, and only 5% of patients experience a recurrence of RCVS.

Development and validation of the mental health professionals' attitude towards people living with HIV/AIDS scale (MHP-PLHIV-AS).

This study focused on the creation and validation of an instrument to measure mental health professionals' attitudes towards people living with HIV/AIDS. Rasch analyses (Rash, 1960, 1980) provided evidence to support a twodimensional (societal and personal dimensions) measurement of this attitude construct.

Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management.

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

Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk.

AIM: To determine epilepsy risk factors after pediatric stroke. METHOD: A cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression. RESULTS: Among 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305). INTERPRETATION: Pediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner.

Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of Stroke Cause and Recurrence.

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

Community-based case-control study of childhood stroke risk associated with congenital heart disease.

BACKGROUND AND PURPOSE: A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based case-control study. METHODS: From 2.5 million children (aged <20 years) enrolled in a Northern California integrated healthcare plan, we identified children with ischemic and hemorrhagic strokes and randomly selected age- and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed before stroke) and used conditional logistic regression to analyze stroke risk factors. RESULTS: CHD was identified in 15 of 412 cases (4%) versus 7 of 1236 controls (0.6%). Cases of childhood stroke (occurring between ages 29 days to 20 years) with CHD had 19-fold (odds ratio, 19; 95% confidence interval 4.2-83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold (odds ratio, 31; confidence interval 4-241) increased risk of stroke in children with CHD when compared with controls. After excluding perioperative strokes, the history of CHD surgery still increased the childhood stroke risk (odds ratio, 13; confidence interval 1.5-114). The majority of children with stroke and CHD were outpatients at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD. CONCLUSIONS: CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside the perioperative period and would benefit from optimized long-term stroke prevention strategies.