Knee Strength and Ankle Range of Motion Impacts on Timed Function Tests in Duchenne Muscular Dystrophy: In the Era of Glucocorticoids

2021 ◽  
pp. 1-13
Author(s):  
Tina Duong ◽  
Jennifer Canbek ◽  
Alicia Fernandez-Fernandez ◽  
Erik Henricson ◽  
Marisa Birkmeier ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Range Of Motion ◽  
Rate Of Change ◽  
Standards Of Care ◽  
Muscle Testing ◽  
Knee Strength ◽  
Function Tests ◽  
Ambulatory Ability ◽  
Loss Of Strength

Background: Duchenne Muscular Dystrophy (DMD) is a neuromuscular disorder that presents in childhood and is characterized by slowly progressive proximal weakness and lower extremity contractures that limit ambulatory ability [1, 2]. Contractures develop in the ankles, knees, and hips due to muscle imbalances, fibrotic changes, loss of strength, and static positioning [2, 5]. Currently, standards of care guidelines emphasize the importance of maintaining good musculoskeletal alignment through stretching, bracing, and glucocorticoid (GC) therapy to preserve strength and function. Methods: This is a retrospective analysis of prospectively collected data through the CINRG Duchenne Natural history study (DNHS). The objectives of this analysis are to understand the progression of ankle contractures for individuals with DMD and to investigate the relationship between progressive lower limb contractures, knee strength, and Timed Function Tests. A collection of TFTs including supine to stand (STS), 10 meter walk test (10MWT), and timed stair climbing (4SC) have been used to monitor disease progression and are predictive of loss of ambulation in these patients [4]. Multiple factors contribute to loss of ambulation, including progressive loss of strength and contracture development that leads to changing biomechanical demands for ambulation. A better understanding of the changes in strength and range of motion (ROM) that contribute to loss of function is important in a more individualized rehabilitation management plan. In this longitudinal study, we measured strength using quantitative muscle testing (QMT) with the CINRG Quantitative Measurement System (CQMS)), ROM was measuresed with a goniometer and TFTs were measured using a standard stopwatch and methodology. Results: We enrolled 440 participants; mean baseline age was 8.9 (2.1, 28.0) years with 1321 observations used for analysis. GC use was stratified based on duration on drug with 18.7%at <  6 months or naïve; 4.3%<1 year; 58.0%1 <  10 years; and 19.3%between 10-25 years of GC use. Ankle ROM was better for those on GC compared to GC naive but did not significantly influence long-term progression rates. QMT, ROM, age and GCs contribute to speed of TFTs. Knee extension (KE) strength and Dorsiflexion (DF) ROM are significant predictors of speed for all TFTs (p <  0.001). Of the variables used in this analysis, KE strength is the primary predictor of walking speed, estimating that every pound increase in KE results in a 0.042 m/s improvement in 10MWT, and a smaller similar increase of 0.009 m/s with every degree of ankle DF ROM. Conclusion: GC use provides an improvement in strength and ROM but does not affect rate of change. Knee strength has a greater influence on speed of TFTs than DF ROM, although both are statistically significant predictors of speed. Results show that retaining knee strength [1, 2], along with joint flexibility, may be important factors in the ability to perform walking, climbing and supine to stand activities.

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

2021 ◽  
pp. 1-14
Author(s):  
Cathleen E. Buckon ◽  
Susan E. Sienko ◽  
Eileen G. Fowler ◽  
Anita M. Bagley ◽  
Loretta A. Staudt ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Genetic Disorder ◽  
Knee Extensor ◽  
Standard Of Care ◽  
Rate Of Change ◽  
Isokinetic Dynamometry ◽  
Gross Motor

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.

Registries versus tertiary care centers: How do we measure standards of care in Duchenne muscular dystrophy?

2016 ◽  
Vol 26 (4-5) ◽  
pp. 261-263 ◽  
Author(s):  
Eugenio Mercuri ◽  
G. Baranello ◽  
R. Battini ◽  
A. Berardinelli ◽  
E. Bertini ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Tertiary Care ◽  
Standards Of Care ◽  
Tertiary Care Centers

Reduced mandibular range of motion in Duchenne Muscular Dystrophy: predictive factors

2015 ◽  
Vol 42 (6) ◽  
pp. 430-438 ◽  
Author(s):  
H. W. van Bruggen ◽  
L. Van Den Engel-Hoek ◽  
M.H. Steenks ◽  
E.M. Bronkhorst ◽  
N.H.J. Creugers ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Range Of Motion ◽  
Predictive Factors

Improving Temporomandibular Range of Motion in People With Duchenne Muscular Dystrophy and Spinal Muscular Atrophy

2020 ◽  
Vol 74 (2) ◽  
pp. 7402205080p1
Author(s):  
Evan Harry Lloyd Morris ◽  
Timothy Estilow ◽  
Allan M. Glanzman ◽  
Stacy Victoria Cusack ◽  
Sabrina W. Yum
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Spinal Muscular Atrophy ◽  
Range Of Motion ◽  
Muscular Atrophy

scholarly journals A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy

Neurology ◽  
2017 ◽  
Vol 89 (17) ◽  
pp. 1811-1820 ◽  
Author(s):  
Ronald G. Victor ◽  
H. Lee Sweeney ◽  
Richard Finkel ◽  
Craig M. McDonald ◽  
Barry Byrne ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Upper Limb ◽  
Low Dose ◽  
Controlled Trial ◽  
High Dose ◽  
Ambulatory Ability ◽  
Efficacy Measure ◽  
Efficacy Measures ◽  
Primary Hypothesis

Objective:To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).Methods:Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg−1·d−1, tadalafil 0.6 mg·kg−1·d−1, or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome.Results:Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p= 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p= 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state.Conclusions:Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age.Clinicaltrials.gov identifier:NCT01865084.Classification of evidence:This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.

scholarly journals New Perspectives on the Diagnosis and Management of Duchenne Muscular Dystrophy

2015 ◽  
Vol 10 (01) ◽  
pp. 73 ◽  
Author(s):  
Francesco Muntoni ◽  
Annemieke Aartsma-Rus ◽  
Eugenio Mercuri ◽  
Hanns Lochmüller ◽  
◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Patient Care ◽  
Neuromuscular Diseases ◽  
Test Reliability ◽  
Standards Of Care ◽  
Specialist Care ◽  
6Mwt Distance ◽  
Care And Treatment ◽  
The Impact

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder that occurs in around one in 5,000 male births. The prevalence of DMD is expected to rise due to improved standards of care and implementation of guidelines, leading to longer survival. Specialist genetic confirmation of a DMD diagnosis is typically followed by access to specialist care and treatment: the exact DMD-causing mutation should be identified because it can influence prognosis and identify patients eligible for treatment. Since the majority of patients has a deletion or duplication of one or more exons (~70 %), generally multiplex ligation-dependent probe amplification suffices to identify the mutation. Exon sequencing is performed to pick up small mutations (~30 %). Greater awareness of DMD is needed among healthcare professionals to enable earlier diagnosis, which would facilitate family planning, as well as patient care and treatment. In DMD patients who are still able to walk, the 6-minute walk test (6MWT) has been shown to be a valid measure of physical functioning and a predictor of disease progression, with high inter-test reliability. In a study of the natural history of DMD, change in 6MWT of around 30 metres has been indicated to be clinically relevant and clinically meaningful. DMD patients responded to treatment as shown by the improvement in the 6MWT score in the large multinational trial of the nonsense mutation readthrough agent, ataluren (Translarna™) 40 mg/kg/day, where treatment was associated with a 31.3 metres improvement on the 6MWT distance, after 48 weeks, compared with placebo. The Translational Research in Europe–Assessment & Treatment of Neuromuscular Diseases (TREAT-NMD) network was launched to provide an infrastructure to accelerate research and therapy development, increasing collaboration, improving patient care and helping to support ‘clinical trial readiness’. As such, the TREAT-NMD registry network is well placed to support further understanding of DMD and the impact of therapies that may be used over the long term, permitting a host of research questions to be explored.

Sign in / Sign up

Export Citation Format

Share Document