Single-centre parental survey of paediatric rehabilitation services for children with cerebral palsy

Cerebral palsy (CP) is the most common childhood motor disability. The dose of usual care for rehabilitation therapies is unknown. The purpose of this study was to describe current dosage of rehabilitation services for children with CP recruited from a paediatric hospital system in the USA. 96 children with CP were included in this cross-sectional survey. Parents reported frequency, intensity, time and type of therapy services. Weekly frequency was the most common. Children with CP received 0.9–1.2 hours/month of each discipline in the educational setting and 1.5–2.0 hours/month in the clinical setting, lower than the recommendations for improvements in motor skills

Retrospective analysis of motor development in infants at high and low risk for autism spectrum disorder

Objective: To measure upper-extremity and gross motor skill development in infants with and without risk factors for autism spectrum disorder (ASD). Method: Data were coded retrospectively from 39 infants who participated in longitudinal structured early developmental assessments. Twenty-five infants were at high risk for ASD, and the remaining 14 infants were classified as low risk. Upper-extremity and motor skill development were coded at ages 2, 4, and 6 mo. Five infants went on to receive an ASD diagnosis at age 2-4 yr. Results: Infants at high risk for ASD demonstrated fewer midline behaviors with the upper extremities and delayed motor skill development than the low-risk group. Differences in motor skills were most apparent at age 4 mo. Conclusion: Early monitoring for motor delay in infants at high risk for ASD is warranted. Midline control and play with the upper extremities and overall motor skill development are possible assessment and therapeutic targets

3D Motion Capture May Detect Spatiotemporal Changes in Pre-Reaching Upper Extremity Movements with and without a Real-Time Constraint Condition in Infants with Perinatal Stroke and Cerebral Palsy: A Longitudinal Case Series

Perinatal stroke (PS), occurring between 20 weeks of gestation and 28 days of life, is a leading cause of hemiplegic cerebral palsy (HCP). Hallmarks of HCP are motor and sensory impairments on one side of the body—especially the arm and hand contralateral to the stroke (involved side). HCP is diagnosed months or years after the original brain injury. One effective early intervention for this population is constraint-induced movement therapy (CIMT), where the uninvolved arm is constrained by a mitt or cast, and therapeutic activities are performed with the involved arm. In this preliminary investigation, we used 3D motion capture to measure the spatiotemporal characteristics of pre-reaching upper extremity movements and any changes that occurred when constraint was applied in a real-time laboratory simulation. Participants were N = 14 full-term infants: N = six infants with typical development; and N = eight infants with PS (N = three infants with PS were later diagnosed with cerebral palsy (CP)) followed longitudinally from 2 to 6 months of age. We aimed to evaluate the feasibility of using 3D motion capture to identify the differences in the spatiotemporal characteristics of the pre-reaching upper extremity movements between the diagnosis group, involved versus uninvolved side, and with versus and without constraint applied in real time. This would be an excellent application of wearable sensors, allowing some of these measurements to be taken in a clinical or home setting

Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by deficient synthesis of dopamine and serotonin. It presents in early infancy, and causes severe developmental disability and lifelong motor, behavioral, and autonomic symptoms including oculogyric crises (OGC), sleep disorder, and mood disturbance. We investigated the safety and efficacy of delivery of a viral vector expressing AADC (AAV2-hAADC) to the midbrain in children with AADC deficiency (ClinicalTrials.gov Identifier NCT02852213). Seven (7) children, aged 4-9 years underwent convection-enhanced delivery (CED) of AAV2-hAADC to the bilateral substantia nigra (SN) and ventral tegmental area (VTA) (total infusion volume: 80 µL per hemisphere) in 2 dose cohorts: 1.3 × 1011 vg (n = 3), and 4.2 × 1011 vg (n = 4). Primary aims were to demonstrate the safety of the procedure and document biomarker evidence of restoration of brain AADC activity. Secondary aims were to assess clinical improvement in symptoms and motor function. Direct bilateral infusion of AAV2-hAADC was safe, well-tolerated and achieved target coverage of 98% and 70% of the SN and VTA, respectively. Dopamine metabolism was increased in all subjects and FDOPA uptake was enhanced within the midbrain and the striatum. OGC resolved completely in 6 of 7 subjects by Month 3 post-surgery. Twelve (12) months after surgery, 6/7 subjects gained normal head control and 4/7 could sit independently. At 18 months, 2 subjects could walk with 2-hand support. Both the primary and secondary endpoints of the study were met. Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function