Cognitive and behavioral functioning in two neurogenetic disorders; how different are these aspects in Duchenne muscular dystrophy and Neurofibromatosis type 1?

The presence of neurocognitive and behavioral problems are common features in various neurogenetic disorders. In Duchenne muscular dystrophy (DMD), these problems have been linked to mutations along the dystrophin gene affecting different brain dystrophin isoforms. However, comparable cognitive and behavioral problems have been found in Neurofibromatosis type 1 (NF1). This study aims to assess disorder specific differences in cognition and behavior between DMD and NF1. Retrospective data of 38 male patients with DMD were aged-matched with data of 38 male patients with NF1. Patients of both groups underwent neurocognitive assessment for regular clinical care. Intellectual abilities, sequential and simultaneous processing, verbal memory and sustained attention were evaluated. In addition, parents and teachers completed behavioral questionnaires. Males with DMD exhibited low intellectual abilities and sequential processing problems, but these outcomes not significantly differed from males with NF1. Simultaneous processing, verbal memory and sustained attention outcomes were equal for both groups. Outcomes of questionnaires displayed higher rates of aggressive behavior (13.2%) in DMD, whereas in NF1 higher rates of problems with thinking (15.8%), withdrawn (10.5%) and social behavior (10.5%) were noticed. In the neurogenetic disorders DMD and NF1, on average overlapping cognitive and behavioral problems are noticed, suggesting that these are not only caused by gene mutations resulting in a lack of one specific protein.

The current practice regarding neuro-prognostication for comatose children after cardiac arrest differs between and within European PICUs: A survey.

PURPOSE: To describe current practices in European Paediatric Intensive Care Units (PICUs) regarding neuro-prognostication in comatose children after cardiac arrest (CA). METHODS: An anonymous online survey was conducted among members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) and the European Paediatric Neurology Society (EPNS) throughout January and February 2019. The survey consisted of 49 questions divided into 4 sections: general information, cardiac arrest, neuro-prognostication and follow-up. RESULTS: The survey was sent to 1310 EPNS and 611 ESPNIC members. Of the 108 respondents, 71 (66%) (23 countries, 45 PICUs) completed the "neuro-prognostication" section. Eight PICUs (20%) had a local neuro-prognostication guideline. The 3 methods considered as most useful were neurological examination (92%), magnetic resonance imaging (MRI) (82%) and continuous electroencephalography (cEEG) (45%). In 50% a Pediatric Cerebral Performance Category (PCPC) score ≥ 4 was considered as poor neurological outcome. In 63% timing of determining neurological prognosis was based on the individual patient. Once decided that neurological prognosis was futile, 55% indicated that withdrawing life-sustaining therapy (WLST) was (one of) the options, whereas 44% continued PICU treatment (with or without restrictions). In 28 PICUs (68%) CA-survivors were scheduled for follow-up visits. CONCLUSION: Local guidelines for neuro-prognostication in comatose children after CA are uncommon. Methods to assess neurological outcome were mainly neurological examination, MRI and cEEG. Consequences of poor outcome differed between respondents. Inaccuracies in neuro-prognostication can result in premature WLST, thereby biasing outcome research and creating a self-fulfilling cycle. Further research is needed to develop scientifically based international guidelines for neuro-prognostication in comatose children after CA.

Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial.

CONTEXT: Neurofibromatosis type 1 (NF1) is among the most common genetic disorders that cause learning disabilities. Recently, it was shown that statin-mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores the cognitive deficits in an NF1 mouse model. OBJECTIVE: To determine the effect of simvastatin on neuropsychological, neurophysiological, and neuroradiological outcome measures in children with NF1. DESIGN, SETTING, AND PARTICIPANTS: Sixty-two of 114 eligible children (54%) with NF1 participated in a randomized, double-blind, placebo-controlled trial conducted between January 20, 2006, and February 8, 2007, at an NF1 referral center at a Dutch university hospital. INTERVENTION: Simvastatin or placebo treatment once daily for 12 weeks. MAIN OUTCOME MEASURES: Primary outcomes were scores on a Rey complex figure test (delayed recall), cancellation test (speed), prism adaptation, and the mean brain apparent diffusion coefficient based on magnetic resonance imaging. Secondary outcome measures were scores on the cancellation test (standard deviation), Stroop color word test, block design, object assembly, Rey complex figure test (copy), Beery developmental test of visual-motor integration, and judgment of line orientation. Scores were corrected for baseline performance, age, and sex. RESULTS: No significant differences were observed between the simvastatin and placebo groups on any primary outcome measure: Rey complex figure test (beta = 0.10; 95% confidence interval [CI], -0.36 to 0.56); cancellation test (beta = -0.19; 95% CI, -0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37); and mean brain apparent diffusion coefficient (beta = 0.06; 95% CI, -0.07 to 0.20). In the secondary outcome measures, we found a significant improvement in the simvastatin group in object assembly scores (beta = 0.54; 95% CI, 0.08 to 1.01), which was specifically observed in children with poor baseline performance (beta = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no significant effect of simvastatin treatment. CONCLUSION: In this 12-week trial, simvastatin did not improve cognitive function in children with NF1. Trial Registration isrctn.org Identifier: ISRCTN14965707.