OBJECTIVE:To determine if children enrolled in the International Pediatric Stroke Study (IPSS) database (4294 patients enrolled, 2003-2014, neonates through 18 years of age) demonstrate demographic, clinical, radiographic, and therapeutic characteristics that relate to age and development at the time of stroke. STUDY DESIGN:Participants with arterial ischemic stroke or cerebral sinus venous thrombosis were enrolled using standardized consent and case report forms. Data were entered on-site and electronically transferred to a central data storage site in Toronto, Canada. Children were stratified into 4 age groups for analysis of developmental features: neonates (0-28 days of age); infants (29 days to <2 years of age); young children (2 years to <10 years old), and adolescents (≥10 years to <18 years old). Continuous and categorical variables were examined using appropriate statistical techniques in SAS (SAS Institute, Inc). RESULTS:Three thousand eight-hundred nine children were analyzed: 1112 (29.2%) neonates, 728 (19.1%) infants, 1088 (28.6%) young children, and 881 (23.1%) adolescents. Arterial ischemic stroke alone occurred in 3201 (916 neonates; 2285 older children) and cerebral sinovenous thrombosis alone occurred in 608 (196 neonates; 412 older children). Age group specific clinical and neuroimaging features that segregate by ischemic stroke type were identified and are reported. CONCLUSIONS:The IPSS database comprises a very large, structured pediatric stroke database used by investigators to advance the understanding and treatment of pediatric stroke. Developmentally based analyses of IPSS data reveal features of childhood stroke that segregate by ischemic stroke type and age at stroke occurrence. These features should aid in understanding age-related pathophysiology and in clinical stroke recognition.

Background: Studies evaluating long-term neurologic outcomes following NAIS are scanty. We aimed to study the emergence pattern of neurologic deficits following NAIS. Methods: Neonates diagnosed with AIS were prospectively enrolled and outcomes were evaluated using the validated Pediatric Stroke Outcome Measure-Severity Classification Scheme. Neurologic outcomes were classified as normal/mild, moderate or severe. Trend analysis was conducted using Cochran-Armitage test. Results: A total of 126 neonates (59% males) were followed for a median of 5.2 years (IQR:3.4-6.4 years). The proportion of children classified as normal/mild declined from 94% to 76% >5 years post-stroke (p<0.01). Moderate and severe outcomes increased from 5% to 15% and 1% to 8% (p=0.01), respectively. Sensorimotor, language and cognitive deficits emerged in 16%, 14%, and 17% of enrolled neonates, respectively. Of those who had normal/mild outcomes at baseline, 83 remained stable throughout the study. Improvement in neurologic outcomes was seen in 8 children. Thirty-five neonates had emerging deficits at one point during follow-up. Congenital heart disease predicted the emergence of deficits (odds ratio=3.3, 95% confidence interval:1.01-10.5). Conclusions: Emerging deficits following NAIS are not uncommon and can equally manifest in sensorimotor, language or cognitive domains. Thus, long-term follow-up and close monitoring of outcomes following NAIS is crucial.

Introduction: Clinical outcome from childhood cerebral sinovenous thrombosis (CSVT), particularly in younger children, is poor. Most studies report “general” neurological outcomes; few describe neuropsychological outcomes. Objectives: To study the spectrum of neuropsychological deficits following childhood CSVT.  Methods: Retrospective analysis of neuropsychological testing (NPT) performed in children with CSVT from 1995-2011. NPT included IQ [Wechsler Intelligence Score for Children (WISC-IV), Wechsler Preschool & Primary Scale of intelligence (WPPSI-III)], executive function [Behaviour Rating Inventory of Executive Function (BRIEF)] and attention [Test of everyday attention (Tea-Ch)]. Full scale IQ (FSIQ) included verbal comprehension (VCI), perceptual reasoning (PRI), working memory (WMI) and processing speed (PSI) index. Results: NPT [mean age: 5.4-years (neonatal CSVT), 8.5-years (non-neonatal CSVT)] was performed in 48/206 patients. Forty-one (34 males) were included [exclusions: cavernous sinus thrombosis (5), prematurity (1), co-existing arterial stroke (1)]. NPT revealed some abnormality in 87% [across one (29%)/multiple (58%) domains] compared to normative population. FSIQ was abnormal in 64% [VCI-69%, PRI-80%, WMI-71%, PSI-79%). FSIQ (p=0.026), VCI (p=0.608), PRI (p= 0.032), WMI (0.124) and PSI (p=0.007) scores were lower. No differences were seen in FSIQ between groups [neonates/non-neonates (p=0.827), single/multiple sinus thrombosis (p=0.2), present/absent parenchymal lesions (p=0.991)] except gender. Males had lower FSIQ (p=0.006) [PRI (p=0.004), WMI (p=0.002), PSI (p=0.002)], BRIEF [metacognition (p=0.061), executive composite (p=0.0950)] and Tea-Ch (p=0.046) scores.  Conclusions: Many childhood CSVT survivors (males > females) have significant residual cognitive deficits detectable only by NPT on long-term follow-up. NPT is indicated for more accurate CSVT outcome assessment.

Idiosyncratic drug induced liver injury (DILI) is a rare adverse drug reaction that poses major challenges to healthcare practitioners and regulatory agencies. We aimed to update the clinical characteristics and outcomes of DILI patients, and the drugs frequently implicated in hepatotoxicity in Spain. We analyzed 915 DILI cases (842 single episodes, 55 re-challenges, 18 double-episodes due to different drugs) in 857 patients included in the Spanish DILI Registry from 1994 to 2015. Cases were adjudicated using expert clinical judgment/RUCAM scale and compared according to pattern of liver damage (hepatocellular, HC; cholestatic, Chol or mixed, Mix). The cohort median age was 57 years (range: 11-90 y) with a mean body mass index of 25.8 ± 3.8 kg/m2. Male gender predominated (52%). HC, Chol and Mix patterns of liver damage were identified in 65%, 18% and 17% of cases, respectively. More than half of the cases were of moderate severity (58%). Patients with Chol and Mix pattern were older (median 64 y and 62 y, respectively) than HC patients (median 52 y), p<0.001. Anti-infectives, central nervous system, cardiovascular and anti-inflammatory agents were the most commonly implicated therapeutic classes accounting for 37%, 14%, 11% and 9% of cases, respectively. Amoxicillin/clavulanate remains the agent responsible for the highest number of DILI (21% of cases). Substantial increase in anabolic androgenic steroid-induced hepatotoxicity was observed in recent years. A cluster of DILI cases reported to the registry (i.e. ebrotidine, tetrabamate, nimesulide, amoxicillin-clavulanate, Exolise®, Epistane®) contributed to adoption of regulatory measures. The pioneering prospective Spanish DILI Registry proved to be very valuable for in-depth clinical phenotyping of hepatotoxicity, providing consistent figures in clinical characteristic outcomes and implicated drugs. It also constitutes an important tool for public health promotion in postmarketing drug surveillance.

Drug-induced liver injury (DILI) remains one of the most challenging diseases due to the absence of diagnostic tests and biomarkers. DILI usually presents as an acute hepatitis-like picture requiring extensive differential diagnosis, hepatitis E virus (HEV), which is considered a rare condition in Spain, is not usually ruled out during acute hepatitis assessment. Analysis of a cohort of 180 patients from the Spanish DILI Registry diagnosed with DILI was undertaken. We analyzed HEV immunoglobulin (Ig) G and M from two groups of serum samples based on the time point of collection (27 samples during the episode of liver damage and 153 at different time points after resolution). In patients showing anti-HEV-IgM+, AgHEV and RNA-HEV were performed. Out of 180 patients included, 60 (33, 3%) were tested positive for anti-HEV IgG and 6 for anti-HEV IgM (1 positive for HEV-RNA and 2 for Ag-HEV). In the group of samples collected during the episode, 3/27 (11%) were positive for IgM-HEV. Table. Demographic and clinical data of patients with positive IgM anti-HEV.Tabled 1Case nºAge (years)SexSuspected DrugLatency (days)Peak ALT(1) or AST(2)HEV RNAAg HEV149FemaleParacetamol91840 (2)NegativePositive274MaleCefditoren404191 (1)PositivePositive326FemaleDexketoprofen81561 (1)NegativeNegative456FemaleIsoniazid27 954 (1)NegativeNegative535MaleErythromycin272469 (1)NegativeNegative675MaleAmoxicillin42967 (1)NegativeNegative Open table in a new tab Evidence of hepatitis E infection is present in a significant number of patients suspected to have DILI. Seroprevalence of IgG HEV is also very high. Hepatitis E should be ruled out in all patients suspected to suffer from DILI in Spain.