Full-time Wheelchair Use Research Articles

Risk Factors for First Fractures Among Males With Duchenne or Becker Muscular Dystrophy.

Fractures are a significant concern for individuals with Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a fracture. Factors that increase or decrease the risk for fracture have been suggested in past research, although statistical risk has not been determined. In this retrospective cohort study, we used the Muscular Dystrophy Surveillance, Tracking and Research Network cohort, a large, population-based sample to identify risk factors associated with first fractures in patients with Duchenne or Becker muscular dystrophy. Our study cohort included males with Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively identified and followed through 2010. We utilized a multivariate Cox proportional hazard model to determine hazard ratios for relevant factors associated with first fracture risk including race/ethnicity, surveillance site, ambulation status, calcium/vitamin D use and duration, bisphosphonate use and duration, and corticosteroid use and duration. Of 747 cases, 249 had at least 1 fracture (33.3%). Full-time wheelchair use increased the risk of first fracture by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval, 1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D use did not significantly affect risk in the final adjusted model. In this cohort, first fractures were common and full-time wheelchair use, but not corticosteroid use, was identified as a risk factor. The impact of prevention measures should be more thoroughly assessed. Fractures are a significant concern for individuals with dystrophinopathies, but the contribution of various risk factors has not been consistently demonstrated.

UK Facioscapulohumeral Muscular Dystrophy (FSHD) Patient Registry

The United Kingdom (UK) Facioscapulohumeral Dystrophy (FSHD) Patient Registry launched in May 2013. Funded by the Muscular Dystrophy Campaign and supported by the TREAT-NMD Alliance. This patient driven registry collects the internationally agreed core dataset, an outcome of an ENMC Workshop held in 2010 [1], through a novel online portal (http://www.fshd-registry.org/uk). Genetic details are added by a nominated neuromuscular specialist. In addition questionnaires about pain, quality of life and scapular fixation are included. In the 12 months between May 2013 and May 2014 over 400 people registered, 92% with a diagnosis of FSHD1. Similar proportions of patients registered from both sexes and 59% of patients were between 40 and 70 years old (mean 47.39). Muscle weakness was widely reported with periscapular shoulder weakness occurring most frequently (89%) followed by weakness of the hip girdle (73%), facial muscles (72%) and foot dorsiflexor (71%). The onset of facial weakness was reported significantly earlier than weakness in other areas with 66% experiencing facial weakness before 20 years old. Full time wheelchair use was reported in 18% of cases, 62% having lost ambulation between 31 and 60 years old (mean 41.61). Use of a wheelchair or other assistive device part time was reported in 44% of cases. A small proportion of patients report hearing loss (18%), retinal vascular disease (2%) and using ventilation (7%). Additional questionnaires on pain were completed by 350 patients during this time and the majority reporting at least some pain, most often described as tiring or aching. Persistent pain (experienced for at least 3 months in a year) was reported by 92% with 53% of people describing this pain as distressing, horrible or excruciating. The location of the pain is variable but most often reported in the shoulder. A broad spectrum of patients has registered providing a new insight into the FSHD population in the UK. The Registry aims to help facilitate and accelerate clinical research and trials, sharing a common dataset with a growing number of FSHD registries around the world will allow the registry to achieve this locally and internationally. The registry is well placed to inform future clinical research and help develop of standards of care.

G.P.312: Intrafamilial variability in GMPPB associated alpha-dystroglycanopathy and broadening of the clinical phenotype

Alpha-dystroglycanopathies (αDGs) represent a heterogeneous group of muscular dystrophies. There are currently 18 known genes leading to forms of alphaDG, with mutations of GDP-mannose pyrophosphorylase B (GMPPB) being one of the most recently described in one case series. The spectrum of reported GMPPB patients spans from severe neonatal to a mild later onset limb-girdle muscular dystrophy (LGMD) phenotype with or without intellectual disability. GMPPB is important for synthesis of GDP-mannose, a mannosyl donor in 4 glycosylation pathways. We present a 3 affected siblings with compound heterozygous mutations (previously described p.Asp27His and novel p.Gln264TER) in GMPPB presenting as LGMD with variable degrees of muscle weakness but a broader spectrum of early intellectual impairment, epilepsy (1 of 3 patients), and ocular findings. Onset and degree of weakness was variable. Patient P1 has severe intellectual disability, cataracts, glaucoma, and a history of intractable epilepsy, but minimal weakness; while patient P2 has severe weakness with near full time wheelchair use since 16 years old. CK level was elevated in all patients (3015–18,685). Muscle biopsy in P2 revealed dystrophic changes with reduced αDG staining. Brain MRI showed mild posterior cortical thinning in P1. Neuropsychological testing revealed variable intellectual disability in all three patients. Muscle imaging revealed variable changes consistent with areas of fatty infiltration. These siblings further contribute to and expand the spectrum of patients with mutations of GMPPB highlighting that motor and cognitive phenotypes associated with GGMPPB related αDGpathy may not directly correlate. Cognitive deficits and epilepsy can precede recognition of muscle symptoms, thus delaying more targeted testing. Simple CK testing may identify a larger cohort of patients with αDGpathy presenting with minimal motor but more severe cognitive or seizure phenotype whose muscle disease had remained undetected.

Online Self-Report Data for Duchenne Muscular Dystrophy Confirms Natural History and Can Be Used to Assess for Therapeutic Benefits

To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings. Further, with the low barrier to participation, we anticipate substantial growth in the dataset in the coming years.

Clinical trial preparedness in facioscapulohumeral dystrophy: Outcome measures and patient access: 8–9 April 2013, Leiden, The Netherlands

Thirty participants from eight countries representing academic centers and advocacy groups met on 8–9 April, 2013 for a workshop on clinical trial preparedness in facioscapulohumeral muscular dystrophy (FSHD). The aims of the workshop were to discuss ways to facilitate patient access to clinical trials and to reach consensus on the development of the most appropriate clinical and surrogate outcome measures for future clinical trials. FSHD is one of the most common forms of muscular dystrophy with a prevalence of 1:15,000–1:20,000 [1,2]. A dominantly inherited disease, in its most common form, FSHD is slowly progressive and causes significant lifetime morbidity, with up to 20% above age 50 requiring full time wheelchair use. The clinical spectrum of disease severity is wide and the regional distribution of muscle weakness and the pattern of progression are unique. Muscle weakness typically starts in the face and shoulders, often with striking side-to-side asymmetry, with a descending progression to involve first the distal lower extremity muscle before affecting the hip girdle muscles. Non muscular involvement in FSHD includes hearing loss and retinal vascular disease, which are typically symptomatic only in patients with the largest deletions.

Fetal Spine Findings on MRI and Associated Outcomes in Children With Open Neural Tube Defects

The purpose of this study is to determine the relationship between abnormal fetal spine findings on MRI and adverse outcomes in children with open neural tube defects. This was a review of pregnancies complicated by myelomeningocele referred for fetal MRI from 2001 to 2007 and followed postnatally at a spina bifida treatment center. MRI scans were reviewed to determine lesion level (T-L2, L3-4, or L5-S), interpediculate distance (≤ 10 or > 10 mm), vertebral segment span, and presence or absence of covering membrane. Ambulation was assessed in children 3 years old or older. Bladder dysfunction was termed as high-risk if renal damage was present or if urodynamic studies indicated increased risk for renal damage. Statistical analyses included chi-square, Mantel-Haenszel test for trend, and logistic regression. MRI was performed in 36 pregnancies with fetal myelomeningocele at a mean (± SD) of 27 ± 6 weeks, with subsequent delivery at 38 ± 1 week. Outcomes were assessed at 3.2 years (range, 2.4-5.1 years), and 23 children were 3 years old or older. Higher lesion level was associated with dysphagia: T-L2, 50%; L3-4, 45%; and L5-S, 13% (p < 0.05). The absence of covering membrane was associated with scoliosis (36% vs 0% with membrane present) and with high-risk bladder dysfunction (71% vs 36%; both p < 0.05). Higher lesion level, larger segment span, and interpediculate distance greater than 10 mm were associated with full-time wheelchair use (all p < 0.05). In fetuses with myelomeningoceles, higher and larger lesions on MRI were significantly associated with full-time wheelchair use. High lesion level was associated with dysphagia. The absence of a covering membrane was associated with scoliosis and high-risk bladder dysfunction.

Use of Corticosteroids in a Population-Based Cohort of Boys With Duchenne and Becker Muscular Dystrophy

The use of corticosteroids for treatment of Duchenne and Becker muscular dystrophy in clinical practice from 1991 through 2005 was reviewed in a large population-based cohort (MD STARnet) of boys in 4 regional sites and 6 clinics of the United States. Corticosteroid use increased from 20% (11 of 56 individuals) in 1991 to 44% (93 of 218 individuals) in 2005. Average use varied by site and ranged from 15% to 49%. The median age of corticosteroid initiation was 6.9 years (range, 3.7-17.4 years). Dosage and growth information was available for 102 participants and showed a median dose as 0.729 mg/kg for prednisone and 0.831 mg/kg for deflazacort. T. The most common reasons that corticosteroids were discontinued included weight gain, behavioral side effects, and loss of ambulation, resulting in full-time wheelchair use. Substantial variations in clinical practice were identified among study sites.

Spina Bifida and Mobility in the Transition Years

Adolescents with spina bifida experience decreased mobility (Johnson KL, Dudgeon B, Kuehn C, et al: Am J Public Health 2007;97:330-6), especially during the time of transition from pediatric to adult care, but little research has been done on the relationships between mobility and self-management skills, psychological health, or quality of life. In this multicenter, interdisciplinary study, a convenience sample of 61 participants with spina bifida from regional spina bifida clinics (mean age = 21.0 +/- 2.1 yrs) participated in a structured clinical interview on self-management and completed standardized self-report measures of psychological distress, quality of life, and mobility status. Participants were divided into three mobility groups: ambulators, part-time wheelchair users, and full-time wheelchair users and were compared with respect to outcome measures. We found that full-time wheelchair use is associated with reduced quality of life but that psychological distress and problems with self-management are prevalent, regardless of mobility status. Research should be aimed at assessing life satisfaction as it relates to assistive technology use to delineate further how technological advancements in wheelchair design and universal design of homes and communities can have the greatest impact on mobility and quality of life.

Serial Manual Muscle Testing in Duchenne Muscular Dystrophy

Serial measurements of muscle strength of 34 muscle groups were obtained for up to a seven-year period using manual muscle testing (MMT) in a group of 63 boys (mean age = 11.5 years) with Duchenne muscular dystrophy (DMD) not using lower extremity bracing or corrective surgery for ambulation, in order to define the natural course of strength loss and its relation to anthropometric variables and ambulatory status. When correlating the first MMT assessment of each patient with age, strength was found to decrease linearly (-0.26 +/- 0.30 MMT units/year) with time until approximately age 14 when a marked decrease in progression was noted (-0.06 +/- 0.03 MMT units/year). Analyzing individual patients longitudinally yielded a similar rate of strength loss. The average muscle score was 3.0 MMT units at the point of full-time wheelchair use. The marked decline in MMT deterioration around age 14 may be an important consideration when assessing the efficacy of therapeutic interventions in adolescent boys with DMD.