Background Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. MethodsWe did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005-2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017-2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France.

Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics. We show that DLG4 (PSD95) protein is synthesised by microglia in immature mouse and human, developmentally regulated, and modulated by inflammation; DLG4 is a hub protein in the microglial inflammatory response; and genetic variation in DLG4 is associated with structural differences in the preterm infant brain. DLG4 is thus apparently involved in brain development and impacts inter-individual susceptibility to injury after preterm birth.

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.

We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.

Disorders of the developing brain represent a major health problem. The neurological manifestations of brain lesions can range from severe clinical deficits to more subtle neurological signs or behavioral problems and learning disabilities, which often become evident many years after the initial damage. These long-term sequelae are due at least in part to central nervous system immaturity at the time of the insult. The blood-brain barrier (BBB) protects the brain and maintains homeostasis. BBB alterations are observed during both acute and chronic brain insults. After an insult, excitatory amino acid neurotransmitters are released, causing reactive oxygen species (ROS)-dependent changes in BBB permeability that allow immune cells to enter and stimulate an inflammatory response. The cytokines, chemokines and other molecules released as well as peripheral and local immune cells can activate an inflammatory cascade in the brain, leading to secondary neurodegeneration that can continue for months or even years and finally contribute to post-insult neuronal deficits. The role of the BBB in perinatal disorders is poorly understood. The inflammatory response, which can be either acute (e.g., perinatal stroke, traumatic brain injury) or chronic (e.g., perinatal infectious diseases) actively modulates the pathophysiological processes underlying brain injury. We present an overview of current knowledge about BBB dysfunction in the developing brain during acute and chronic insults, along with clinical and experimental data.

Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukomalacia) is the predominant form in premature infants and the most common antecedent of cerebral palsy. Stem cell treatment has proven effective in restoring injured organs and tissues in animal models. The potential of stem cells for self-renewal and differentiation translates into substantial neuroprotection and neuroregeneration in the animal brain, with minimal risks of rejection and side effects. Stem cell treatments described to date have used neural stem cells, embryonic stem cells, mesenchymal stem cells, umbilical cord stem cells, and induced pluripotent stem cells. Most of these treatments are still experimental. In this review, we focus on the efficacy of stem cell therapy in animal models of cerebral palsy, and discuss potential implications for current and future clinical trials.

Objectives: Minor infection can trigger adult arterial ischemic stroke (AIS) and is common in childhood. We tested the hypotheses that infection transiently increases risk of AIS in children, regardless of stroke subtype, while vaccination against infection is protective. Methods:The Vascular Effects of Infection in Pediatric Stroke study is an international casecontrol study that prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years old) and 354 stroke-free controls. To determine prior exposure to infections and vaccines, we conducted parental interviews and chart review.Results: Median (interquartile range) age was 7.6 years for cases and 9.3 for controls (p 5 0.44).Infection in the week prior to stroke, or interview date for controls, was reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk of AIS (p , 0.0001); upper respiratory infections were most common. Prevalence of preceding infection was similar across stroke subtypes: arteriopathic, cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly low in both groups. Children with some/few/no routine vaccinations were at higher stroke risk than those receiving all or most (odds ratio [OR] 7.3, p 5 0.0002). In an age-adjusted multivariate logistic regression model, independent risk factors for AIS included infection in the prior week (OR 6.3, p , 0.0001), undervaccination (OR 8.2, p 5 0.0004), black race (compared to white; OR 1.9, p 5 0.009), and rural residence (compared to urban; OR 3.0, p 5 0.0003).Conclusions: Infection may act as a trigger for childhood AIS, while routine vaccinations appear protective. Hence, efforts to reduce the spread of common infections might help prevent stroke in children. Neurology ® 2015;85:1459-1466 GLOSSARY AIS 5 arterial ischemic stroke; CI 5 confidence interval; IQR 5 interquartile range; OR 5 odds ratio; PFO 5 patent foramen ovale; SES 5 socioeconomic status; VIPS 5 Vascular Effects of Infection in Pediatric Stroke.

The presence of migraine in children and adolescents aged 6 to 18 years was associated with a history of infantile colic. Additional longitudinal studies are required.