Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

Population-based study of ischemic stroke risk after trauma in children and young adults.

OBJECTIVE:To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. METHODS:We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. RESULTS:From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). CONCLUSIONS:Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Treatment efficacy for infantile epileptic spasms syndrome in children with trisomy 21

BackgroundInfantile Epileptic Spasms Syndrome (IESS) is the most common epilepsy syndrome in children with trisomy 21. First-line standard treatments for IESS include adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Among children with trisomy 21 and IESS, treatment with ACTH or oral corticosteroids may yield higher response rates compared with vigabatrin. However, supporting data are largely from single-center, retrospective cohort studies.MethodsLeveraging the multi-center, prospective National Infantile Spasms Consortium (NISC) database, we evaluated the efficacy of first-line (standard) treatments for IESS in children with trisomy 21. We assessed clinical spasms remission at two weeks, clinical spasms remission at three months, and improvement of EEG (resolution of hypsarrhythmia) three months after initiation of treatment.ResultsThirty four of 644 (5.3%) children with IESS were diagnosed with trisomy 21. In all children with trisomy 21, epileptic spasms was their presenting seizure type. Twenty of 34 (59%) children were initially treated with ACTH, nine (26%) with oral corticosteroids, and five (15%) with vigabatrin. Baseline demographics did not vary among treatment groups. The overall clinical remission rate after two weeks of treatment was 53% including 13 of 20 (65%) receiving ACTH, three of nine (33%) receiving oral corticosteroids, and two of five (40%) receiving vigabatrin (p = 0.24). The continued clinical response rate at three months was 32% including 8 of 20 (40%) receiving ACTH, two of nine (22%) receiving oral corticosteroids, and one of five (20%) receiving vigabatrin. Thirty of the 34 (88%) children presented with hypsarrhythmia (88%). EEG improvement at three months was better for children treated with ACTH (74%) or oral corticosteroids (83%) than vigabatrin (20%; p = 0.048). Adjustment for time from epileptic spasms onset to treatment did not alter results.ConclusionsIn our cohort, epileptic spasms were the first presenting seizure type in all children with trisomy 21. Among first-line standard treatment options, ACTH may have superior efficacy for clinical and electrographic outcomes for IESS in children with trisomy 21

The use of chest ultrasonography in suspected cases of COVID-19 in the emergency department

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases. Patients & methods: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods. Results: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%. Conclusion: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19. The gold standard for diagnosis of COVID-19 is RT-PCR. During a pandemic emergency, it may be useful to identify suspect symptomatic patients who may safely be observed without undergoing testing for COVID-19. In this work, a simple model based on the findings of lung ultrasound, AST levels and fever showed an overall accuracy of 91% to predict the results of RT-PCR

Neonatal Seizures and Associated Neurobehavioral Profiles in Preschool Age Children

BackgroundNeonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone.MethodsNeonates with acute provoked seizures born from July 2015 to March 2018 were enrolled at nine Neonatal Seizure Registry sites. Composite scores from parent-completed standardized ratings assessed Adaptive, Social, Externalizing, Internalizing, Self-Regulation, and Sensory Seeking domains. Linear regression demonstrated relationships between composite scores for children who developed postneonatal epilepsy compared with those who did not. Results were adjusted for seizure etiology, sex, gestational age, and cerebral palsy (CP) severity.ResultsA total of 151 children (n = 20, 13% with postneonatal epilepsy), 4.1 years median age, participated. Children with epilepsy had impaired adaptive (Cohen d = 1.62, P < 0.0001), social (Cohen d = 0.86, P = 0.004), and executive functioning (Cohen d = 0.56, P = 0.06) compared with children without epilepsy. Mean scores for children without epilepsy were within average range. Risk for impairment among children with epilepsy persisted after adjusting for neonatal seizure etiology, sex, and gestational age, but not when adjusting for CP severity.ConclusionsThere was higher incidence of adverse neurobehavioral outcomes among preschool children diagnosed with postneonatal epilepsy compared with those without epilepsy. CP severity was associated with greater impairment; results also suggest that epilepsy is an independent predictor of adaptive functioning. Children with postneonatal epilepsy should be screened for neurobehavioral problems to facilitate early identification and developmental support

Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans

Preferred Parental Language and Neurodevelopmental Outcomes Among Infants With Acute Provoked Neonatal Seizures in the United States

BackgroundParental non-English language preference (NELP) is associated with worse pediatric health outcomes. However, little is known about its relationship with developmental outcomes in infants with neonatal seizures. This study evaluated the relationship between parental NELP and neurodevelopment in a multicenter cohort of infants with neonatal seizures.MethodsInfants in the Neonatal Seizure Registry-II were included. Parental NELP was defined by the use of a professional interpreter for research consent and survey completion. The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment was conducted at age 24 months. Multivariate regression was used to examine the association between parental NELP and WIDEA-FS. Functional developmental impairment was defined as a WIDEA-FS score 2 S.D.s below the normative mean.ResultsAmong 270 infants with neonatal seizures, 15 (6%) had parental NELP. Children with parental NELP had a WIDEA-FS score that was on average 13 points lower than that of infants without parental NELP (95% confidence interval [CI]: -27 to 1, P = 0.08) and over five times the odds of functional developmental impairment (odds ratio 4.9, 95% CI: 1.3 to 18.4, P = 0.017).ConclusionsChildren with parental NELP were more likely to have functional developmental impairment at age 24 months when compared with children without parental NELP. Since parental NELP does not have a biologically plausible impact on neurodevelopment it likely reflects discriminatory experiences that affect developmental opportunities. These findings highlight the importance of identifying social drivers to decrease potential gaps in neurodevelopmental attainment for children with parental NELP