Longitudinal community walking activity in Duchenne muscular dystrophy.

INTRODUCTION: Natural history studies for Duchenne muscular dystrophy (DMD) have not included measures of community ambulation. METHODS: Step activity (SA) monitors quantified community ambulation in 42 boys (ages 4-16 years) with DMD with serial enrollment up to 5 years by using a repeated-measures mixed model. Additionally, data were compared with 10-meter walk/run (10mWR) speed to determine validity and sensitivity. RESULTS: There were significant declines in average strides/day and percent strides at moderate, high and pediatric high rates as a function of age (P < 0.05). Significant correlations for 10mWR versus high and low stride rates were found at baseline (P < 0.05). SA outcomes were sensitive to change over 1 year, but the direction and parameter differed by age group (younger vs. older). Changes in strides/day and percentages of high frequency and low frequency strides correlated significantly with changes in 10mWR speed (P < 0.05). DISCUSSION: Community ambulation data provide valid and sensitive real-world measures that may inform clinical trials. Muscle Nerve 57: 401-406, 2018.

A Longitudinal Study of Quantitative Muscle Strength and Functional Motor Ability in Ambulatory Boys with Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7-13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care. OBJECTIVE: The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures. METHODS: Eighty-four ambulatory boys with DMD (49-180 months), 70 on CS, 14 corticosteroid naïve (NCS), participated in this 8-year multi-site study. Outcomes included; isokinetic dynamometry, the Standing (STD) and Walking/Running/jumping (WRJ) dimensions of the Gross Motor Function Measure (GMFM), and Timed Function Tests (TFTs). Nonlinear mixed modeling procedures determined the rate of change with age and the influence of steroids. RESULTS: Despite CS therapy the rate of decline in strength with age was significant in all muscle groups assessed. CS therapy significantly slowed decline in knee extensor strength, as the NCS group declined at 3x the rate of the CS group. Concurrently, WRJ skills declined in the NCS group at twice the rate of the CS group. 4-stair climb and 10 meter walk/run performance was superior in the boys on CS therapy. CONCLUSION: CS therapy slowed the rate of muscle strength decline and afforded longer retention of select gross motor skills in boys on CS compared to boys who were NCS. Isokinetic dynamometry, Walk/Run/Jump skills, and select TFTs may prove informative in assessing the efficacy of new therapeutics in ambulatory boys with DMD.

Efficacy of corticosteroid in decreasing scoliosis and extending time to loss of ambulation in a single clinic: an effectiveness trial.

PURPOSE: Pharmacologic doses of corticosteroid (CS) have been shown to ameliorate the progression of Duchenne muscular dystrophy (DMD) preserving strength, pulmonary function and ambulation as well as reducing the incidence of scoliosis. However, there are serious side effects of CS, which may impact dose tolerance. The purpose of this study was to compare the magnitude of positive CS effects on patients in our clinic to those reported in the literature. METHODS: We retrospectively reviewed medical records and radiographs of 142 DMD patients who were seen between 1st January 1991 and 31st December 2017. RESULTS: In total, 101 boys met study inclusion criteria. Of these 32 were steroid naïve, 37 took the recommended dose (standard of care, SOC) of Prednisone or Deflazacort, and 32 took a lower dose (LD). Following initiation of CS, both treatment groups showed an increase in weight velocity and decrease in linear growth velocity. Although there was a trend to later loss of ambulation (LOA) in the SOC group relative to the naïve group by one year, this was not significant, however, a small subgroup of boys on Deflazacort showed a 3.4 year later LOA than the naïve group. The incidence of scoliosis was reduced from 69% in the naïve, to 41% in the LD and 47% in the SOC group. CONCLUSIONS: Although there was a reduction in the incidence of scoliosis, it was not as robust as seen elsewhere. Many published studies have inadequate data on scoliosis probably due to the lack of inclusion of orthopaedists in the study group. LEVEL OF EVIDENCE: IV.

An exploratory study investigating the multidimensional factors impacting the health and well-being of young adults with cerebral palsy.

BACKGROUND: For young adults with cerebral palsy, changes in psychological and social development, in conjunction with the progression of musculoskeletal deformities and the onset of secondary conditions, make the transition to adulthood a difficult developmental phase. Preliminary evidence shows that many of the physical impairments reported in adults with cerebral palsy begin during late adolescence; however, there is little information about prevalence of impairments and the combined role impairments, psychological and social factors have on the health and well-being of young adults with cerebral palsy. METHODS: A cross-sectional, multidimensional survey approach was used to examine the ambulatory decline, pain, pain interference, depression, fatigue, locus of control, emotional support, overall health status and satisfaction with life of young adults with cerebral palsy, age 18-30 years. RESULTS: Ninety-seven surveys (57 self-report and 40 proxy report) were completed across all gross motor function classification system levels. No significant differences were found amongst functional levels for pain, pain interference, fatigue or depression. Only pain interference significantly contributed to the variance in health status, while emotional support significantly contributed to the variance in satisfaction with life. CONCLUSIONS: The large percentage of young adults in this study reporting pain, fatigue and depression indicates that the onset of these impairments may begin at an earlier age. This study found that emotional support from family facilitates improved health status and enhanced satisfaction with life in young adults with cerebral palsy. Similar to physical impairments, social and psychological factors also contribute to the health and well-being of young adults with cerebral palsy, a holistic approach to care that includes preventative strategies to address both mental and physical health outcomes should begin well in advance to their transition into young adulthood in order to mitigate the impact these factors have on health and well-being during this critical developmental time. Implications for Rehabilitation Pain, fatigue and depression were reported for all levels of GMFCS and should be assessed and addressed with appropriate treatment early in order to determine whether there are surgical, pharmacological, rehabilitative or counseling services that could be implemented at a younger age to improve outcomes in young adulthood. For young adults with CP, emotional support plays a significant role in the health status and satisfaction with life and strategies to enhancing support beyond the family could enhance health status and satisfaction with life.