Recent Advances in Neuropsychological Outcomes and Intervention in Pediatric Stroke.

Over the past 15 years, there have been significant advances in the treatment of acute and chronic medical consequences of stroke in childhood. Given high rates of survival in pediatric stroke, practitioners are tasked with treating the ongoing motor and neuropsychological sequelae in patients over the course of their development. This article provides a review of the current literature on neuropsychological outcomes in pediatric stroke, including intelligence, academics, language, visual-spatial skills, attention, executive functions, memory, and psychosocial function. Recent developments in functional neuroimaging are discussed, with a particular focus on language outcomes. We further review the current research on cognitive and behavioral rehabilitation and introduce intervention models in pediatric stroke. In the final section, we discuss future directions for clinical practice and research in pediatric stroke.

Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate.

UNLABELLED: Glycerol phenylbutyrate is under development for treatment of urea cycle disorders (UCDs), rare inherited metabolic disorders manifested by hyperammonemia and neurological impairment. We report the results of a pivotal Phase 3, randomized, double-blind, crossover trial comparing ammonia control, assessed as 24-hour area under the curve (NH3 -AUC0-24hr ), and pharmacokinetics during treatment with glycerol phenylbutyrate versus sodium phenylbutyrate (NaPBA) in adult UCD patients and the combined results of four studies involving short- and long-term glycerol phenylbutyrate treatment of UCD patients ages 6 and above. Glycerol phenylbutyrate was noninferior to NaPBA with respect to ammonia control in the pivotal study, with mean (standard deviation, SD) NH3 -AUC0-24hr of 866 (661) versus 977 (865) µmol·h/L for glycerol phenylbutyrate and NaPBA, respectively. Among 65 adult and pediatric patients completing three similarly designed short-term comparisons of glycerol phenylbutyrate versus NaPBA, NH3 -AUC0-24hr was directionally lower on glycerol phenylbutyrate in each study, similar among all subgroups, and significantly lower (P < 0.05) in the pooled analysis, as was plasma glutamine. The 24-hour ammonia profiles were consistent with the slow-release behavior of glycerol phenylbutyrate and better overnight ammonia control. During 12 months of open-label glycerol phenylbutyrate treatment, average ammonia was normal in adult and pediatric patients and executive function among pediatric patients, including behavioral regulation, goal setting, planning, and self-monitoring, was significantly improved. CONCLUSION: Glycerol phenylbutyrate exhibits favorable pharmacokinetics and ammonia control relative to NaPBA in UCD patients, and long-term glycerol phenylbutyrate treatment in pediatric UCD patients was associated with improved executive function (ClinicalTrials.gov NCT00551200, NCT00947544, NCT00992459, NCT00947297). (HEPATOLOGY 2012).

Functional magnetic resonance imaging of working memory and response inhibition in children with mild traumatic brain injury.

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and "real world" measures of executive functioning, but not on traditional "paper and pencil" tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data.

Neuropsychological implications of Cobalamin C (CblC) disease in Hispanic children detected through newborn screening.

Cobalamin C (CblC) disease is the most common inborn error of cobalamin metabolism and recent data has indicated a higher prevalence among children of Hispanic heritage in particular. The purpose of this study was to (a) describe the neuropsychological characteristics of a pilot sample of Hispanic children with CblC disease and (b) explore potential differences in outcome based on underlying genetic mutation(s) and biochemical levels. Six Hispanic children (ages 2-10) diagnosed with CblC disease through newborn screening (NBS) underwent neuropsychological evaluation with a bilingual examiner. Biochemical levels and underlying mutation(s) were obtained through medical records. The overall sample performed below normative expectations across neuropsychological domains, including general cognition, adaptive functioning, language ability, and visual-motor integration. Underlying mutations and associative clinical phenotypes were found to significantly predict general cognitive abilities, while plasma methionine and Hcy at the time of diagnosis were significantly correlated with language outcomes. Despite limited sample size, results indicate that Hispanic children with CblC disease detected through NBS and treated early experience neuropsychological deficits even when treated with current standard treatments. However, consistent with prior research in non-Hispanic children with CblC disease, underlying mutations and early biochemical levels may predict better outcomes in this population as well.

Executive functioning profiles from the BRIEF across pediatric medical disorders: Age and diagnosis factors.

The objective of the study was to compare executive functioning (EF) profiles across several pediatric medical conditions and explore the influence of age of diagnosis and evaluation. A retrospective, cross-sectional study of 734 children aged 5 to 18 years was conducted across five medical groups (brain tumor, leukemia [ALL], epilepsy [EPI], neurofibromatosis type 1 [NF1], and ornithine transcarbamylase deficiency [OTC-D]), attention deficit hyperactivity disorder (ADHD) controls, and matched healthy controls. We compared groups across the scales of a parent-completed Behavior Rating Inventory of Executive Functioning (BRIEF) using a repeated measures analysis of variance (ANOVA). Separate ANOVAs were conducted to look at age factors. The results showed that the ADHD group differed from all other groups and had the highest level of reported EF problems. The NF1 and OTC-D groups differed significantly from the healthy comparison group for overall EF problems, while the EPI and cancer groups did not. Working memory was the most elevated scale across medical groups, followed by plan/organize. Children with medical disorders were two to four times more likely than healthy controls to have clinically significant problems in several EF domains. There was a main effect for age at diagnosis and age at evaluation. A subset of children with medical disorders were found to have parent-reported EF difficulties, with particular vulnerability noted in working memory and organizational/planning skills. This has relevance for the development of interventions that may be helpful across disorders. Children with particular diagnoses and earlier age of diagnosis and evaluation had greater reported EF problems.