Clinical and biological progress over 50 years in Rett syndrome

In the 50 years since Andreas Rett first described the syndrome that came to bear his name, and is now known to be caused by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, a compelling blend of astute clinical observations and clinical and laboratory research has substantially enhanced our understanding of this rare disorder. Here, we document the contributions of the early pioneers in Rett syndrome (RTT) research, and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation, and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, considering the lessons learned from both cell and animal models, and how they might inform future clinical trials. With a focus on the core criteria, we examine the relationships between genotype and clinical severity. We review current knowledge about the many comorbidities that occur in RTT, and how genotype may modify their presentation. We also acknowledge the important drivers that are accelerating this research programme, including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we highlight the major milestones since 1966, and what they mean for the day-to-day lives of individuals with RTT and their families

Assessing the Risk-Benefit Ratio of Scoliosis Surgery in Cerebral Palsy: Surgery Is Worth It

BACKGROUND: The true benefits of scoliosis surgery in cerebral palsy (CP) remain uncertain. Our aims were to determine the benefits of spinal fusion according to health-related quality of life (HRQoL) improvement at long-term follow-up and to explore the effect of surgery-related complications on clinical outcomes. METHODS: The cases of consecutive patients who had Gross Motor Function Classification System (GMFCS) level-IV or V cerebral palsy with 5-year follow-up from a prospective, longitudinal, multicenter database were analyzed. Caregivers completed the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire and 4 Likert-type anchor questions preoperatively and at 1, 2, and 5 years of follow-up. Data on complications were collected prospectively. Preoperative CPCHILD scores were compared with postoperative scores at the 1, 2, and 5-year follow-up evaluations. Preoperative CPCHILD scores were compared with postoperative scores at the 1, 2, and 5-year follow-up evaluations using repeated-measures analysis of variance (ANOVA). Spearman correlation coefficient was used to explore the association between changes in the CPCHILD at 1, 2, and 5-year follow-up and the reported complications within the follow-up period. Similarly, a comparative analysis between the percentage distribution of the answers to the 4 anchor questions and the reported complications was also performed. RESULTS: Sixty-nine patients with a mean age (and standard deviation) of 13.4 ± 2.6 years at enrollment were analyzed. The major Cobb angle was a mean of 81.9° ± 26.7° preoperatively and improved to a mean of 28.7° ± 14.4° at 2 years and 30.7° ± 15.3° at 5 years postoperatively. Significant improvements in CPCHILD personal care, positioning, and comfort domains were noted at all time points. The mean increase in the total score was 7.19 (p < 0.001) at 1 year, and the score gain was maintained at 2 and 5 years postoperatively. The overall complication rate was 46.4% at 1 year, 1.4% between 1 and 2 years, and 4.3% at 2 to 5 years postoperatively, with surgical intervention required in 6 patients within 1 year and in 2 additional patients within 5 years following scoliosis surgery. There was no correlation between complications and CPCHILD scores postoperatively at all time points, with the only exception of a weak correlation (ρ = -0.450, p = 0.002) with CPCHILD comfort score at 1 year after surgery. CONCLUSIONS: Scoliosis surgery in patients with CP leads to a significant improvement in HRQoL, which is maintained 5 years following surgery. The substantial complication rate does not correlate with HRQoL changes postoperatively, suggesting that the benefits of surgery outweigh the risks in this fragile population. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Pediatric scoliosis

Pediatric scoliosis is a relatively uncommon condition typically first noticed due to altered stature or by routine spine screenings by a school nurse or pediatrician. The formal diagnosis is made with spine radiographs, with coronal curvature measurement of 10° or greater. Treatment may consist of serial observation, bracing until skeletal maturity, or surgery for correction and fusion/stabilization of severe or progressive deformity. Overall success for non-operative management of scoliosis is affected by the etiology for the deformity, close follow up and monitoring for evolution of the deformity, and patient compliance with their treatment regimen. The most common surgical technique is a posterior approach spine fusion with implanted instrumentation, and patients are typically back to their activities of daily living by 6 months postoperatively. Continued intermittent monitoring of the scoliosis throughout adulthood is recommended, to detect late deformity progression, development of arthritis symptoms, or other associated issues