Neurological Outcome In Children Research Articles

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study

IntroductionIn light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their...

Abstract TP96: Association Between Infarct Volume, Neighborhood-Level Deprivation, and Outcomes in Pediatric Stroke

Introduction: Recent studies in adults have reported an association between neighborhood-level deprivation, infarct volume and outcome. However, this is yet to be investigated in pediatric arterial ischemic stroke (AIS). Our study aimed to assess the relationship between neighborhood-level deprivation, infarct volume, and neurological outcome in children diagnosed with AIS. Methods: We conducted a study of a consecutive cohort of children aged > 28 days-18 years and diagnosed with AIS between 2004 and 2019 at a comprehensive stroke center. Patient demographic, clinical characteristics and neighborhood material deprivation data including household income, parental educational attainment, the proportion of single-parent families, and housing quality were collected. Lesion volumes were determined by conducting semi-automatic segmentation of diffusion-weighted MRI brain scans at stroke presentation. Neurological outcome was assessed using the Pediatric Stroke Outcome Measure Severity Classification System wherein poor outcome was defined as moderate-to-severe deficit at 18 months post-stroke. Wilcoxon rank sum test was conducted. Results: Seventy-two patients were included in the study (62% male, median age of stroke onset 6.1 years [IQR 1.0-12.7]). 39% of patients were White, 72% lived in an urban region, and 64% in highly deprived neighborhoods. 70% of patients arrived within 6 hours from onset of stroke. Cardiac disease and other risk factors including infection and head trauma represented the most common risk factor. 55% presented with moderate stroke severity (as per the PedNIHSS). Median lesion volume was 14 cm 3 (IQR 2-51) and a mean infarct volume of 3% was reported. Race, rurality, and neighborhood-level material deprivation were not significantly associated with either percent infarct volume or neurological outcome; however, percent infarct volume was significantly associated with neurological outcome at 18 months post-stroke (W = 79, p = 0.025). Conclusion: Our study findings confirm the relationship between infarct volume and pediatric AIS outcomes. Future multi-center studies are warranted to further understand the interplay between material deprivation, infarct volume, and post-AIS neurological outcomes in children.

Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy

BackgroundAcute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. MethodsAll patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. ResultsTwenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). ConclusionsFerritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.

Hydroxyurea Improves Intelligence Quotient Scores in Children with Sickle Cell Anemia and Elevated Transcranial Doppler Velocity

Introduction: Structural brain abnormalities resulting from sickle cell disease because of strokes, silent cerebral infarcts (SCI) and other biophysical characteristics of parenchymal damage from repeated sickling affect cognitive functioning. Hydroxyurea therapy reduces transcranial Doppler (TCD) velocities and improves SCI and other neurological outcomes in children with sickle cell anaemia. Hence the objectives of EXpanding Treatment for Existing Neurological Disease (EXTEND, NCT02556099), a phase 2 clinical trial, was to determine whether hydroxyurea titrated to maximum tolerated dose was effective in lowering transcranial Doppler (TCD) velocities and improving cognitive function in Jamaican children with sickle cell anemia (SCA) with increased stroke risk. Methods: Full-Scale Intelligence Quotient (FSIQ), verbal and nonverbal IQ were measured with the Wechsler Abbreviated Scale of Intelligence (WASI-II) at baseline and after 18 months of hydroxyurea treatment in 30 of the 43 enrolled children. Verbal Comprehension Index (VCI) was assessed using the Vocabulary and Similarities subtests. Perceptual Reasoning Index (PRI) was scored with the Block Design and Matrix Reasoning subtests. Members of the team conducting the tests were trained and test results were verified by an experienced member of the Epidemiology Research Unit, Caribbean Institute for Health Research. Participants were enrolled in the EXTEND trial based on a pre-treatment conditional or abnormal TCD velocity. They were assigned to one of three risk categories according to treatment status and stroke history at study enrollment: Group 1 (low stroke risk: no previous stroke, on hydroxyurea treatment n= 12), Group 2 (medium stroke risk: no previous stroke, no hydroxyurea, n=10) and Group 3 (High stroke risk: previous stroke, no hydroxyurea n=8). Anthropometric variables, including height and weight, were recorded as well as oxygen saturation and hematological variables. Differences in post treatment outcome were modelled using mixed linear regression. A p-value of &amp;lt;0.05 was considered statistically significant. Results: There was no difference in mean anthropometric values or gender distribution at baseline by stroke risk category groups (Table 1). The mean(sd) age in years of participants in Group 1 was 8.2(1.7), while for Group 2 the average age was 7.7(2.1) and for Group 3 it was 10.5(2.8). The mean age of Group 3 was significantly greater than Group 1. After 18 months of hydroxyurea treatment, participants were taking an average dose of 25 mg/kg/d, range 13.7 to 34.9 mg/kg/d. On treatment TCD velocities decreased by mean(sd) of 29.5 cm/sec (31.5). Hemoglobin (Hb) concentration was lowest in Group 3 but all groups showed increases during treatment with the rate of increase in Groups 2 and 3 being greater than Group 1 (p&amp;lt;0.001). Absolute neutrophil counts and absolute reticulocyte counts were not different by group, and both decreased significantly post treatment (p&amp;lt;0.001) (Table 1). At both time points, the VCI, PRI and FSIQ mean scores in Group 3 were low [Overall means(sd); 71(11.7), 71(12.6),69(11.6), respectively] and were significantly lower compared with Group 1 (p&amp;lt;0.001) (Table 1). While there was no significant effect of treatment on VCI and PRI scores, the mean FSIQ score increased on average by 2.9 units (95%CI 0.3, 5.4) post treatment among participants. Adjusting for age at enrollment had no effect on the improvement on FSIQ, however adjusting for changes in hemoglobin resulted in an increase in FSIQ by 3.3 units (95%CI -0.4, 7.0) which approached statistical significance (p=0.079). Conclusion: Participants treated with hydroxyurea at maximum tolerated dose for 18 months with or without a previous stroke had significant improvement in hematological variables and neuropsychological scores. Children with sickle cell anemia with high risk of stroke may benefit from routine neuropsychological testing, hydroxyurea treatment in addition to educational interventions.

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial

ObjectiveTo investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.DesignPhase 3b multicentre, double-blind, randomised placebo-controlled trial.SettingTwenty-one hospitals in the UK.ParticipantsChildren aged...

Electroencephalogram pattern predicting neurological outcomes of children with seizures secondary to abusive head trauma

BackgroundThe clinical presentations of abusive head trauma can abruptly worsen, so the occurrence of seizures and changes of EEG can be variable according to patients’ conditions. Since the changes of EEG background waves reflect the cortical function of children, we aimed to find out whether the timing of EEG background, epileptiform discharges and seizure patterns were associated with the outcomes of patients with AHT. Material and methodsUsing seizure type and acute stage electroencephalographic (EEG) characteristics to assess adverse neurological outcomes in children with seizures secondary to abusive head trauma (AHT). Children who were hospitalized with AHT at a tertiary referral hospital from October 2000 to April 2010 were evaluated retrospectively. A total of 50 children below 6 years of age admitted due to AHT were included. KOSCHI outcome scale was used to evaluate the primary outcome and neurological impairment was used as secondary outcome after 6 months discharge. ResultsChildren with apnea, cardiac arrest, reverse blood flow and skull fracture in clinic had a higher mortality rate even in the no-seizure group (3/5 [60%] vs. 3/45 [6.7%], odds ratio [OR] = 11; 95% CI = 2.3–52; p = 0.025). Seizure occurrence reduced mostly at the second day after admission in seizure groups; but children with persistent seizures for 1 week showed poor neurological outcomes. The occurrence of initial seizure was frequency associated with younger age; focal seizure, diffuse cortical dysfunction in acute-stage EEG, and low Glasgow Coma Scale (GCS) score were significantly related to poor outcomes after 6 months. Diffuse cortical dysfunction was also associated with motor, speech, and cognitive dysfunction. ConclusionsDiffuse cortical dysfunction in acute-stage EEG combined with low GCS score and focal seizure may related to poor outcomes and neurological dysfunctions in children with AHT.

Measuring the impact of deprivation on learning difficulties and behaviour among infants born preterm: A cohort study.

Preterm birth and social deprivation are known risk factors for learning difficulties. However there has been little work looking into the interaction between these two risks. We aimed to identify if children born preterm to families with higher levels of social deprivation are disproportionately more likely to have learning difficulties than those with lower levels of social deprivation. Data from the RANOPS (Respiratory And Neurological Outcomes in children born Preterm Study) was used to assess prevalence of learning difficulties. The effects of preterm birth and deprivation were reviewed. Multi-level logistic regression models were used to examine if gestational age and deprivation impacts interacted after adjustment for possible confounders. Primary outcome measure was parent-reported learning difficulties. Secondary outcome measures were parent-reported behavioural problems and a statement of special educational need. We investigated the developmental outcomes of 6,691 infants with a median age of 5 years at time of survey (IQR 5). Deprivation decile (OR 1.08 (1.03,1.12)) and preterm birth (OR 2.67 (2.02,3.53)) were both associated with increased risk of learning difficulties. There was little evidence for any interaction between preterm birth and deprivation (p = 0.298) and the risk of learning difficulties. Deprivation and preterm birth have significant associations with learning difficulties. While deprivation does not appear to have potentiated the impact of preterm birth, preterm infants in the most deprived areas have the highest risk of learning difficulties with almost 1 in 3 extremely premature infants with a learning difficulty in the most deprived areas.

Seizures in Pediatric Moyamoya: Risk Factors and Functional Outcomes

BackgroundChildren with moyamoya arteriopathy are at high risk for stroke and seizures. Risk factors for seizures and the impact of seizures on neurological outcomes in children with moyamoya are unknown. MethodsThis is a single-center retrospective cohort study of children with moyamoya evaluated between 2003 and 2021. Functional outcome was assessed using the Pediatric Stroke Outcome Measure (PSOM). Associations between clinical variables and seizure occurrence were assessed using univariate and multivariable logistic regression. Associations between clinical variables and final PSOM score were assessed using ordinal logistic regression. ResultsEighty-four patients met inclusion criteria, and 34 (40%) children experienced seizure. Factors associated with seizures included moyamoya disease (vs syndrome; odds ratio [OR] 3.43, P = 0.008) and the presence of infarcts on baseline neuroimaging (OR 5.80, P = 0.002). Factors associated with decreased likelihood of experiencing seizures included older age at initial presentation (OR 0.82, P = 0.002) and asymptomatic (radiographic) presentation (OR 0.05, P = 0.006). Both older age at presentation (adjusted OR [AOR] 0.80, P = 0.004) and incidental radiographic presentation (AOR 0.06, P = 0.022) remained significant after adjusting for potential confounders. Seizures were associated with worse functional outcomes as assessed by the PSOM (regression coefficient 2.03, P < 0.001). This association remained significant after adjusting for potential confounders (adjusted regression coefficient 1.54, P = 0.025). ConclusionsYounger age and symptomatic presentation are associated with increased likelihood of seizures among children with moyamoya. Seizures are associated with worse functional outcomes. Prospective studies should clarify how seizures impact outcomes and how effective seizure treatment modifies this relationship.

Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism caused by an activating GLUD1 mutation. The aim of this study was to determine the clinical profile and long-term neurological outcomes in children with HI/HA syndrome. This study is a retrospective review of patients with GLUD1 mutation, treated at two centers in the UK and Russia, over a 15-year period. Different risk factors for neuro-developmental disorders were analysed by Mann-Whitney U test and Fisher's exact P test. We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 h-18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. Twenty four cases responded to diazoxide and protein restriction whilst one patient underwent partial pancreatectomy. In total, 13 cases (52%) developed neurodevelopmental manifestations. Epilepsy (n = 9/25, 36%), learning difficulties (n = 8/25, 32%) and speech delay (n = 8/25, 32%) were the most common neurological manifestation. Median age of presentation for epilepsy was 12 months with generalised tonic-clonic seizures being the most common (n = 4/9, 44.4%) followed by absence seizures (n = 3/9, 33.3%). Early age of presentation (P = 0.02), diazoxide dose (P = 0.04) and a mutation in exon 11 or 12 (P = 0.01) were associated with neurological disorder. HI/HA syndrome is associated with wide spectrum of neurological disorders. These neurological manifestations were more frequent in cases with mutations affecting the GTP-binding site of GLUD1 in our cohort.

Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.

To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.

Abstract Number ‐ 48: Cerebral Sinus Venous Thrombosis Secondary to Chronic Inflammatory Disorders in Children

Introduction Cerebral Sinus Venous Thrombosis (CSVT) is a rare form of venous thromboembolism that can lead to significant morbidity and mortality predominantly in young people. While previous literature has identified prothrombotic and infectious pathologies as significant risk factors for CSVT, chronic systemic conditions such as connective tissue diseases (CTD) are less studied. The purpose of the current study is to describe the clinical features, neuroimaging characteristics, treatment, and long‐term neurological outcomes in children with CSVT secondary to CTD. Methods We reviewed electronic medical records of patients under 18 years of age diagnosed with CSVT secondary to CTD between 2002–2018 in a single center. We analyzed data regarding demographics, comorbidities, neuroimaging and neurological examination findings during the initial encounter. Subsequent long‐term follow‐up neurological examinations, lab and imaging workup, and medical management was also analyzed. Results Eight patients (Male:Female: 6:2) met the criteria and were included in the analysis. The patient’s age ranged from 6 weeks to 17 years. CTDs include Behcet’s (n = 2), Kawasaki (n = 1), systemic lupus erythematosus (n = 1), Wegener granulomatosis (n = 1), sarcoidosis (n = 1), and inflammatory bowel disease (n = 1). Five patients had a normal neurological examination on initial presentation, two had papilledema, and one had hypotonia and poor suck reflex. On initial neuroimaging, the most common thrombosis locations were transverse sinuses (n = 7). All patients received anti‐thrombolytic therapy (heparin, warfarin, or Lovenox) between 2.5 to 6 months. Three patients had complete resolution and one had partial resolution of thrombosis on follow‐up neuroimaging (average = 4.3 months, range 3–8 months). On long‐term clinical follow‐up (average: 41.3 months, SD: 62.1), all patients had normal neurological examinations. Conclusions Our case series demonstrated that 50% of patients with CSVT secondary to CTD showed full/partial resolution of thrombosis on follow‐up neuroimaging. In addition, they also had good clinical outcomes on long‐term clinical follow‐up with anticoagulation or antithrombotic treatment. This study uncovers the favorable outcomes of CSVT associated with CTD in children, but more cohort studies are required in order to make accurate conclusions.

Cerebral Oxygen Saturation in Pediatric Patients On ECMO

Investigators from Johns Hopkins University School of Medicine report that decreased cerebral regional oxygenation saturation (rSO2) was associated with higher mortality and poor short-term neurologic outcomes in children supported on extracorporeal membrane oxygenation (ECMO).

Development and Validation of a Prognostic Model and Bedside Score for the Neurological Outcome in Children with Tuberculous Meningitis.

Only a few studies have explored prognostic factors for tuberculous meningitis (TBM) in children, and an easily applicable bedside prognostic score for TBM has not been developed yet. We compared the sociodemographic, clinical, radiological, and cerebrospinal fluid parameters in the cohort of 94 TBM cases aged 1 to 18 years, with at least 6 months of completed follow-up and determined the prognostic factors associated with poor functional outcome. We assessed our proposed prognostic model using both discrimination and calibration and subsequently used the bootstrap method to validate the model internally. We finally derived an easily applicable bedside prognostic score by rounding off the regression coefficients to the nearest integers. A total of 39 (41%) and 55 (59%) patients had poor and good functional outcomes, respectively, at the end of 6 months (12 died, 13%). In multivariate analysis, a high baseline Pediatric Cerebral Performance Category (PCPC) score, brain infarction in neuroimaging, tonic motor posturing, younger age, and stage III TBM were independent predictors of poor functional outcomes. The final model showed good discrimination (area under the curve = 88.2%, P < 0.001) and good calibration (Hosmer-Lemeshow test, P = 0.53). Bootstrapping also confirmed the internal validity of this model. The PITAS (PCPC score [P], brain infarction in neuroimaging [I], tonic motor posturing [T], age [A], and stage of TBM [S]) score developed from this model has a score ranging from 0 to 12, with a higher score predicting a higher risk of poor functional outcome. The PITAS score performed better than medical research council staging alone in predicting poor functional outcomes (area under the curve = 87.1% versus 82.3%). Our study's PITAS score, developed and internally validated, has good sensitivity and specificity in predicting poor functional outcomes in pediatric TBM cases at 6 months.

Limbic pathway vulnerability associates with neurologic outcome in children after cardiac arrest

AimTo analyze whether brain connectivity sequences including diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (rsfMRI) identify vulnerable brain regions and networks associated with neurologic outcome after pediatric cardiac arrest. MethodsChildren aged 2 d-17 y with cardiac arrest were enrolled in one of 2 parent studies at a single center. Clinically indicated brain MRI with DTI and rsfMRI and performed within 2 weeks after arrest were analyzed. Tract-wise fractional anisotropy (FA) and axial, radial, and mean diffusivity assessed DTI, and functional connectivity strength (FCS) assessed rsfMRI between outcome groups. Unfavorable neurologic outcome was defined as Pediatric Cerebral Performance Category score 4–6 or change > 1 between 6 months after arrest vs baseline. ResultsAmong children with DTI (n = 28), 57% had unfavorable outcome. Mean, radial, axial diffusivity and FA of varying direction of magnitude in the limbic tracts, including the right cingulum parolfactory, left cingulum parahippocampal, corpus callosum forceps major, and corpus callosum forceps minor tracts, were associated with unfavorable neurologic outcome (p < 0.05). Among children with rsfMRI (n = 12), 67% had unfavorable outcome. Decreased FCS in the ventromedial and dorsolateral prefrontal cortex, insula, precentral gyrus, anterior cingulate, and inferior parietal lobule were correlated regionally with unfavorable neurologic outcome (p < 0.05 Family-Wise Error corrected). ConclusionDecreased multimodal connectivity measures of paralimbic tracts were associated with unfavorable neurologic outcome after pediatric cardiac arrest. Longitudinal analysis correlating brain connectivity sequences with long term neuropsychological outcomes to identify the impact of pediatric cardiac arrest in vulnerable brain networks over time appears warranted.

Factors associated with poor neurological outcome in children after abusive head trauma: A multicenter retrospective study

BackgroundAbusive Head Trauma (AHT) remains the leading cause of brain injury in infants. ObjectiveThis study aims to describe a cohort of patients with AHT and identify early risk factors associated with poor neurological outcome. Participants and settingChildren under one year old admitted to a Pediatric Intensive Care Unit (PICU) with a suspected or confirmed diagnosis of AHT were included. Neurological outcome was assessed by the Pediatric Overall Performance Category score (POPC) at discharge from the hospital and at two years of follow-up. MethodsA multicentre retrospective study was conducted over 8 years (from January 2012 to December 2020). ResultsA total of 117 patients (mean age 4.3 (+/− 2.5) months, 61 % boys) from three PICUs were included. A total of 99 (85 %) patients completed a 2-year follow-up. Sixty-one (52 %) and 47 (40 %) children with AHT had a POPC (pediatric overall performance category) score ≥ 2 at discharge from ICU and discharge from hospital, respectively (meaning they had at least a moderate disability). Fifty-one (44 %) had a POPC score ≥ 2 at 2-year follow-up, including 19 patients (19 %) with severe disabilities. The main neurological disabilities were neurodevelopmental (n = 38, 35 %), hyperactivity disorder (n = 36, 33 %) and epilepsy (n = 34, 31 %). After analysis according to the hierarchical model, the occurrence of a cardiorespiratory arrest and a low Glasgow Coma Score at admission stand out as factors of poor neurological outcome. ConclusionThis study highlights the wide range of neurological disabilities in children with AHT. Early and multidisciplinary follow-up is crucial to limit the impact of neurological disability.

Neuroimaging and neurological outcome of children with acute encephalitis.

AimTo investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis.MethodChildren with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years–11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re‐evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short‐term (<3 months from discharge) follow‐up, and at long‐term (>1 year from discharge) follow‐up was assessed from medical records using the Glasgow Outcome Scale.ResultsLong‐term recovery was poor in 24 of 82 (29%) children with follow‐up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re‐evaluation from 74 of 82 patients with follow‐up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery.InterpretationThe risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings.What this paper adds Poor long‐term recovery was found in 29% of children with encephalitis.Severe disability measured by Glasgow Outcome Scale was found in 8%.The most severe neuroimaging findings were a risk factor for severe acute illness and poor long‐term recovery.

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.

Pediatric ECMO: unfavorable outcomes are associated with inflammation and endothelial activation.

Background:Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO.Methods:We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ, interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course.Results:All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition.Conclusions:High levels of circulating inflammatory, endothelial activation and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO.

Effects of the L-tyrosine-derived bacterial metabolite p-cresol on colonic and peripheral cells.

Specific families of bacteria present within the intestinal luminal content produce p-cresol from L-tyrosine. Although the hosts do not synthesize p-cresol, they can metabolize this compound within their colonic mucosa and liver leading to the production of co-metabolites including p-cresyl sulfate (p-CS) and p-cresyl glucuronide (p-CG). p-Cresol and its co-metabolites are recovered in the circulation mainly conjugated to albumin, but also in their free forms that are excreted in the urine. An increased dietary protein intake raises the amount of p-cresol recovered in the feces and urine, while fecal excretion of p-cresol is diminished by a diet containing undigestible polysaccharides. p-Cresol in excess is genotoxic for colonocytes. In addition, in these cells, this bacterial metabolite decreases mitochondrial oxygen consumption, while increasing the anion superoxide production. In chronic kidney disease (CKD), marked accumulation of p-cresol and p-CS in plasma is measured, and in renal tubular cells, p-cresol and p-CS increase oxidative stress, affect mitochondrial function, and lead to cell death, strongly suggesting that these 2 compounds act as uremic toxins that aggravate CKD progression. p-Cresol and p-CS are also suspected to play a role in the CKD-associated adverse cardiovascular events, since they affect endothelial cell proliferation and migration, decrease the capacity of endothelial wound repair, and increase the senescence of endothelial cells. Finally, the fact that concentration of p-cresol is transiently increased in young autistic children biological fluids, and that intraperitoneal injection of p-cresol in animal models induces some behavioral characteristics observed in the autism spectrum disorders (ASD), raise the view that p-cresol may possibly represent one of the components involved in ASD etiology. Further pre-clinical and clinical studies are obviously needed to determine if the lowering of p-cresol and/or p-CS circulating concentrations, by dietary and/or pharmacological means, would allow, by itself or in combination with other interventions, to improve CKD progression and associated cardiovascular outcomes, as well as some neurological outcomes in children with an early diagnosis of autism.

Associations of initial haemodynamic profiles and neurological outcomes in children with traumatic brain injury: a secondary analysis

IntroductionInitial low systolic blood pressure (SBP) in paediatric traumatic brain injury (TBI) is associated with mortality. There is limited literature on how other haemodynamic parameters including heart rate (HR); diastolic...