Children with sickle cell anemia have a high prevalence of silent cerebral infarcts (SCIs) that are associated with decreased full-scale intelligence quotient (FSIQ). While the educational attainment of parents is a known strong predictor of the cognitive development of children in general, the role of parental education in sickle cell anemia along with other factors that adversely affect cognitive function (anemia, cerebral infarcts) is not known. We tested the hypothesis that both the presence of SCI and parental education would impact FSIQ in children with sickle cell anemia. A multicenter, cross-sectional study was conducted in 19 US sites of the Silent Infarct Transfusion Trial among children with sickle cell anemia, age 5–15 years. All were screened for SCIs. Participants with and without SCI were administered the Wechsler Abbreviated Scale of Intelligence. A total of 150 participants (107 with and 43 without SCIs) were included in the analysis. In a multivariable linear regression model for FSIQ, the absence of college education for the head of household was associated with a decrease of 6.2 points (P=0.005); presence of SCI with a 5.2 point decrease (P=0.017); each $1000 of family income per capita with a 0.33 point increase (P=0.023); each increase of 1 year in age with a 0.96 point decrease (P=0.023); and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point decrease (P=0.030). In conclusion, FSIQ in children with sickle cell anemia is best accounted for by a multivariate model that includes both biologic and socioenvironmental factors.
Background and Purpose The implementation of uniform nomenclature and classification in adult arterial ischemic stroke (AIS) has been critical for defining outcomes and recurrence risks according to etiology and in developing risk-stratified treatments. In contrast, current classification and nomenclature in childhood AIS are often overlapping or contradictory. Our purpose was to develop a comprehensive consensus-based classification system for childhood AIS. Methods Utilizing a modified-Delphi method, members of the International Pediatric Stroke Study (IPSS) developed the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria. Two groups of pediatric stroke specialists from the IPSS classified seven test cases using two methods each: 1) classification typical of the individual clinician’s current clinical practice, 2) classification based on the CASCADE criteria. Group 1 underwent in-person training in the utilization of the CASCADE criteria. Group 2 classified the same cases via an online survey including definitions but without training. Inter-rater reliability (IRR) was assessed via multi-rater unweighted kappa statistic. Results In Group 1 (with training), IRR was improved using CASCADE criteria (κ=0.78, 95% CI=[0.49, 0.94]) compared to typical clinical practice (κ=0.40, 95%CI=[0.11, 0.60]). In Group 2 (without training), IRR was lower than among trained raters, (κ=0.61, 95%CI=[0.29,0.77]); but higher than current practice (κ=0.23, 95%CI=[0.03,0.36]). Conclusions A new, consensus-based classification system for childhood AIS, the CASCADE criteria, can be used to classify cases with good IRR. These preliminary findings suggest that the CASCADE criteria may be particularity useful in the setting of prospective multicenter studies in childhood-onset AIS, where standardized training of investigators is feasible.
Background and Purpose Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported five-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods The Vascular effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009–2014, and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of stroke etiologies, including arteriopathies. Other predictors were measured via parental interview or chart review. Results Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0–3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% CI 4.6–10%) at one month and 12% (8.5–15%) at one year. The sole predictor of recurrence was presence of an arteriopathy, which increased the risk of recurrence 5-fold compared to an idiopathic AIS (hazard ration 5.0, 95% CI 1.8–14). The one-year recurrence rate was 32% (95% CI 18–51%) for moyamoya, 25% (12–48%) for transient cerebral arteriopathy, and 19% (8.5–40%) for arterial dissection. Conclusions Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.
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
Discrimination among the vast array of odors requires that the brain discern which of the numerous odorant receptors have been activated. If individual olfactory neurons express only a subset of the odorant receptor repertoire, then the nature of a given odorant can be discerned by identifying which cells have been activated. We performed in situ hybridization experiments demonstrating that individual olfactory neurons express different complements of odorant receptors and are therefore functionally distinct. Thus, a topographic map, defining either the positions of specific neurons in the epithelium or the positions of their projections, may be employed to determine the quality of an olfactory stimulus. Neurons expressing specific receptors appear to be randomly distributed within the olfactory epithelium. These data are consistent with a model in which randomly dispersed olfactory neurons with common receptor specificities project to common glomeruli in the olfactory bulb.
We hypothesized that the silent cerebral infarcts (SCI), which affect up to 40% of children with sickle cell disease (SCD), could occur in the setting of acute anemic events. In a prospective observational study of children with and without SCD hospitalized for an illness associated with acute anemia, we identified acute silent cerebral ischemic events (ASCIE) in 4 (18.2%) of 22 with SCD and in 2 (6.7%) of 30 without SCD, using diffusion-weighted magnetic resonance imaging. Children with ASCIE had lower hemoglobin concentration than those without (median 3.1 vs 4.4 g/dL, P ؍ .003). The unique temporal features of stroke on diffusionweighted magnetic resonance imaging permit estimation of incidence rates for ASCIE of 421 (95% confidence interval, 155-920) per 100 patient-years during acute anemic events for all patients. For children with SCD, the estimated incidence was 663 (95% confidence interval, 182-1707) which is much higher than previously reported. Acute anemic events are common in children with SCD and prevalence could partially account for the high SCI. Some ASCIE (1 of 4 in our study) may be reversible. Alterations in management may be warranted for children with severe anemia to identify unrecognized ischemic brain injury that may have permanent neurocognitive sequelae. (Blood. 2012;120(19):3891-3897)
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