Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

An innovative cycling exergame to promote cardiovascular fitness in youth with cerebral palsy.

OBJECTIVE: To evaluate the effects of an internet-platform exergame cycling programme on cardiovascular fitness of youth with cerebral palsy (CP). METHODS: In this pilot prospective case series, eight youth with bilateral spastic CP, Gross Motor Functional Classification System (GMFCS) level III, completed a six-week exergame programme. Outcomes were obtained at baseline and post-intervention. The primary outcome measure was the GMFCS III-specific shuttle run test (SRT-III). Secondary outcomes included health-related quality of life (HQL) as measured by the KIDSCREEN-52 questionnaire, six-minute walk test, Wingate arm cranking test and anthropomorphic measurements. RESULTS: There were significant improvements in the SRT-III (t = -2.5, p = 0.04, d = 0.88) post-intervention. There were no significant changes in secondary outcomes. CONCLUSION: An exergame cycling programme may lead to improvement in cardiovascular fitness in youth with CP. This study was limited by small sample size and lack of a comparison group. Future research is warranted.

Further evaluation of the scoring, reliability, and validity of the Hypertonia Assessment Tool (HAT).

We assessed the impact of videotape analysis on scoring of the Hypertonia Assessment Tool (HAT) that discriminates between hypertonia subtypes. The HAT was administered to 28 children with cerebral palsy (mean age 9 years, range 4-17 years, 61% male). HAT examinations were videotaped; scores were assigned before and after videotape review. Neurological examination provided the gold standard diagnosis. Interrater reliability, criterion validity and individual item validation were assessed using prevalence and bias-adjusted kappa (PABAK). Videotape review did not significantly change the HAT item scores or diagnoses. Item validation eliminated 1 dystonia item. Interrater reliability was moderate for dystonia (PABAK = 0.43) and excellent for spasticity and rigidity (PABAK = 0.86-1.0). Criterion validity was substantial for spasticity (PABAK = 0.71), moderate for dystonia (PABAK = 0.43-0.57) and excellent for the absence of rigidity (PABAK = 1.0). The HAT can be administered without videotape review. Dystonia item 1 did not change the HAT hypertonia diagnosis and will be removed from the HAT.

Interactive computer play as "motor therapy" for individuals with cerebral palsy.

The aim of the study was to evaluate the quality of evidence for interactive computer play (ICP) to improve motor performance (including motor control, strength, or cardiovascular [CVS] fitness) in individuals with cerebral palsy. A computer-assisted literature search was completed, focusing on ICP as a therapeutic modality to improve motor outcomes in individuals of all ages with cerebral palsy with a specific focus on upper and lower extremity motor outcomes and promotion of CVS fitness. Articles were classified according to American Academy of Neurology guidelines and recommendation classifications were given based on the levels of evidence. Seventeen articles underwent full-text review including 6 on upper extremity motor function, 5 on lower extremity motor function, 1 on CVS fitness, and 5 on studies with a combination of upper or lower extremity or CVS fitness focus or both. Overall, there was level B (probable) evidence for ICP interventions to improve lower extremity motor control or function. However, there was inadequate evidence (level U) for ICP interventions improving upper limb motor control or function or CVS fitness. Although promising trends are apparent, the strongest level of evidence exists for the use of ICP to improve gross motor outcomes. Additional evidence is warranted especially when evaluating the effect of ICP on upper limb motor outcomes and CVS fitness.

Development of the Hypertonia Assessment Tool (HAT): a discriminative tool for hypertonia in children.

AIM: The aim of this study was to develop a tool to identify paediatric hypertonia subtypes. METHOD: Items generated by experts were subscaled (spasticity, dystonia, rigidity). The tool was administered to 34 children (19 males, 15 females, mean age 8y 2mo, range 2y 5mo-18y 7mo) with hypertonia and cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels: I, n=7; II, n=5; III, n=7 level IV, n=7; and level V, n=8 level. Kuder-Richardson Formula 20 determined internal consistency. To assess reliability, two physicians administered the tool to 25 additional children with CP (15 males, 10 females; mean age 10y 8 mo; GMFCS levels I, n=4; II, n=3; III, n=7; IV, n=4; and V, n=7) on two occasions, 2 weeks apart. To evaluate validity, a third physician diagnosed the hypertonia by neurological examination. RESULTS: The internal consistency of the spasticity items was moderate (alpha = 0.58), and dystonia was high (a=0.79). Item reduction eliminated seven of the 14 original items. The agreement of the spasticity and rigidity subscales was adequate (prevalence-adjusted bias-adjusted kappa [PABAK] ranging from moderate [0.57] to excellent [1.0]) for validity, test-retest reliability, and interrater reliability. For dystonia agreement was lower, with PABAK ranging from fair (0.30) to good (0.65). Eighty-seven per cent had spasticity and 78% had dystonia. INTERPRETATION: The Hypertonia Assessment Tool has good reliability and validity for identifying spasticity and the absence of rigidity, and moderate findings for dystonia.

Initial development and validation of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD).

This paper reports the development and validation of a disease-specific measure of health status and well-being of children with severe cerebral palsy (CP). The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) was constructed from recommendations from caregivers, healthcare providers, and review of other measures. Items spanning six domains are rated on an ordinal scale. Standardized scores (0-100) are reported for each domain and in total. Primary caregivers (n = 77) of 45 males and 32 females between 5 and 18 years of age (mean age 13 y 5 mo [SD 3 y 4 mo]) with CP, categorized by the Gross Motor Function Classification System (GMFCS) level, completed the CPCHILD. Caregivers of children with severe CP (GMFCS Levels IV and V) also completed a second administration of the CPCHILD 2 weeks after the first. The mean CPCHILD score for children with severe CP was 56.2 (SD 15.7; range 24-93). The mean CPCHILD scores for children in GMFCS Levels I to V were 22.0, 38.2, 23.0, 44.5, and 59.3 respectively (p < 0.001). Reliability was tested in 41/52 caregivers who reported no change in health status between the two administrations of the CPCHILD. The intraclass correlation coefficient was 0.94 (95% confidence interval 0.90-0.97). The CPCHILD seems to be a reliable and valid measure of caregivers' perspectives on the health status, functional limitations, and well-being of these children.