Cross-cultural adaptation and test-retest reliability of the Italian version of the Pediatric Balance Scale in children with typical and atypical development.

BACKGROUND: Balance disorders in children are complex and disabling. The pediatric balance scale assesses functional balance in the contest of everyday tasks. It is recommended for balance assessment in children. The cross-cultural validation of an assessment instrument allows to assess individuals in the appropriate cultural context. We designed our study with the aim of translating and cross-cultural adapting the Pediatric Balance Scale into Italian, and investigating the reliability of the translated version. METHODS: Two forward translation of the Pediatric Balance Scale were conducted. Two blind backward translations were subsequently performed. A multidisciplinary group compared the content of the translations with those of the original Pediatric Balance Scale. Ambiguities and discrepancies were amended. To assess conceptual equivalence of the translation, we conducted cognitive debriefing involving physiotherapists, parents, and children. Suggestions for rewording were sought and considered for eventual modification. The Italian Pediatric Balance Scale was administered to 18 children with typical development (age 4.7-7.9 years, female 61.1%, scores 51-56), and to 18 children with atypical development (age 4.9-15.0 years, female 44.4%, scores 38-56). Test-retest reliability (i.e., intrarater and interrater reliability, and agreement between raters) of the scale was assessed by mean of single-rating, absolute-agreement, two-way mixed effects model intra-class correlation coefficients (ICC3,1) and the Bland-Altman method. The standard error of measurement and the minimal detectable change were subsequently computed. RESULTS: The forward and backward translations showed no substantial differences in content; wording discrepancies were resolved by consensus. The multidisciplinary group proposed some minor changes. Twenty-three physiotherapists, 36 parents, and 36 children participated in cognitive interviewing and further changes were made. Perfect agreement was observed in test-retest reliability assessment of the Italian pediatric balance scale in children with typical development. High reliability (intrarater: ICC3,1 0.998, 95% CI 0.994 to 0.999; interrater: ICC3,1 0.994, 95% CI 0.984 to 0.998) and agreement among raters (Bland-Altman plots: 89%, 95% CI 67% to 97%, of the data within the 95% CI limits of the bias estimate) were found assessing children with atypical development. Very small standard error of measurement and the minimal detectable change values were observed (intrarater: 0.212 and 0.588; interrater: 0.368 and 1.019). CONCLUSIONS: The present study provides a translated and cross-culturally adapted Italian version of the Pediatric Balance Scale. The full cross-cultural validity of the tool requires further steps to complete the psychometric testing.

Prevention of hip dislocation in severe cerebral palsy (GMFCS III-IV-V): an interdisciplinary and multi-professional Care Pathway for clinical best practice implementation.

BACKGROUND: Hip displacement (HD) and dislocation in severe Cerebral Palsy (CP) (GMFCS III, IV, V) are important causes of worsening disability and quality of life. Prevention must be started from the first months of life through screening programs and early treatments, both conservative and surgical. Evidence from Clinical Practice Guidelines also suggests the development of Care Pathways for good clinical practice. At the beginning of 2020 an interdisciplinary, multi-professional working group, composed of 26 members (including Physiatrists, Physiotherapist, Neuro-psychomotor Therapists and Orthopedists representing the respective Italian Scientific Societies) with the involvement of the FightTheStroke Foundation families' association, was set up. AIM: The aim of the multi-professional panel was the production of evidence-based recommendations for the Care Pathway "Prevention of Hip Displacement in children and adolescents with severe CP" for best clinical practice implementation in our national context. DESIGN: Clinical Care Pathway (Clinical Practice Guideline). SETTING: Inpatient and outpatient. POPULATION: Children with severe CP (GMFCS III-IV-V). METHODS: The recommendations of this Care Pathway were developed using the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) guidelines for Care Pathways development and the Grading of Recommendations Assessment Development and Evaluation (GRADE ADOLOPMENT) working group for adoption or adaption or de novo development of recommendations from high-quality guidelines. In 2020 a multidisciplinary working group (WG) developed four research questions on the prevention of HD on the following topics: screening, botulinum toxin treatment, postural management and preventive soft tissue surgery. A comprehensive review of the biomedical literature was performed on each question. Guidelines, Systematic Reviews and Primary studies were retrieved through a top-down approach. References were screened according to inclusion criteria and quality was assessed by means of specific tools. A list of recommendations was then produced divided by intervention (screening programs, postural management, botulinum toxin, preventive surgery). In a series of meetings, the panel graduated recommendations using the GRADE evidence to decision frameworks. RESULTS: Fifteen recommendations were developed: seven on screening programs, four on postural management strategies, one on botulinum toxin, and three on preventive surgery. Evidence quality was variable (from very low to moderate) and only a few strong recommendations were made. CONCLUSIONS: In severe CP at high risk of hip dislocation, it is strongly recommended to start early hip surveillance programs. In our national context, there is a need to implement Screening programs and dedicated Network teams. We also strongly recommend a comprehensive approach shared with the families and goal-oriented by integrating the different therapeutic interventions, both conservative and not, within Screening programs. CLINICAL REHABILITATION IMPACT: Implementing a comprehensive multi-professional approach for the prevention of hip dislocation in severe CP.

Functional characterization of ryanodine receptor (RYR1) sequence variants using a metabolic assay in immortalized B-lymphocytes.

Mutations in the RYR1 gene are linked to malignant hyperthermia (MH), central core disease and multi-minicore disease. We screened by DHPLC the RYR1 gene in 24 subjects for mutations, and characterized functional alterations caused by some RYR1 variants. Three novel sequence variants and twenty novel polymorphisms were identified. Immortalized lymphoblastoid cell lines from patients with RYR1 variants and from controls were stimulated with 4-chloro-m-cresol (4-CmC) and the rate of extracellular acidification was recorded. We demonstrate that the increased acidification rate of lymphoblastoid cells in response to 4-CmC is mainly due to RYR1 activation. Cells expressing RYR1 variants in the N-terminal and in the central region of the protein (p.Arg530His, p.Arg2163Pro, p.Asn2342Ser, p.Glu2371Gly and p.Arg2454His) displayed higher activity compared with controls; this could account for the MH-susceptible phenotype. Cell lines harboring RYR1(Cys4664Arg) were significantly less activated by 4-CmC. This result indicates that the p.Cys4664Arg variant causes a leaky channel and depletion of intracellular stores. The functional changes detected corroborate the variants analyzed as disease-causing alterations and the acidification rate measurements as a means to monitor Ca(2+)-induced metabolic changes in cells harboring mutant RYR1 channels.

Identification of new polymorphisms in the CACNA1S gene.

We identified four novel polymorphisms in the CACNA1S gene that encodes the alpha1-subunit of the dihydropyridine receptor. Mutations in this gene are associated with two genetic diseases: malignant hyperthermia and hypokalemic periodic paralysis. The nucleotide substitutions c2403T --> C and c5398T --> C did not result in amino acid replacement, the nucleotide substitution c4475C --> A caused the replacement of the Ala1492 with an Asp residue and an A insertion was identified in intron 36. By using methods based on digestion with restriction enzymes we calculated the frequencies of these novel polymorphisms, as well as heterozygosity, in normal subjects from southern Italy.