Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy

Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age.

The aim of this study was to describe systematically the best available intervention evidence for children with cerebral palsy (CP). This study was a systematic review of systematic reviews. The following databases were searched: CINAHL, Cochrane Library, DARE, EMBASE, Google Scholar MEDLINE, OTSeeker, PEDro, PsycBITE, PsycINFO, and speechBITE. Two independent reviewers determined whether studies met the inclusion criteria. These were that (1) the study was a systematic review or the next best available; (2) it was a medical/allied health intervention; and (3) that more than 25% of participants were children with CP. Interventions were coded using the Oxford Levels of Evidence; GRADE; Evidence Alert Traffic Light; and the International Classification of Function, Disability and Health. Overall, 166 articles met the inclusion criteria (74% systematic reviews) across 64 discrete interventions seeking 131 outcomes. Of the outcomes assessed, 16% (21 out of 131) were graded 'do it' (green go); 58% (76 out of 131) 'probably do it' (yellow measure); 20% (26 out of 131) 'probably do not do it' (yellow measure); and 6% (8 out of 131) 'do not do it' (red stop). Green interventions included anticonvulsants, bimanual training, botulinum toxin, bisphosphonates, casting, constraint-induced movement therapy, context-focused therapy, diazepam, fitness training, goal-directed training, hip surveillance, home programmes, occupational therapy after botulinum toxin, pressure care, and selective dorsal rhizotomy. Most (70%) evidence for intervention was lower level (yellow) while 6% was ineffective (red). Evidence supports 15 green light interventions. All yellow light interventions should be accompanied by a sensitive outcome measure to monitor progress and red light interventions should be discontinued since alternatives exist. © 2013 Mac Keith Press.

Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.