Gait classification for growing children with Duchenne muscular dystrophy.

Classifying gait patterns into homogeneous groups could enhance communication among healthcare providers, clinical decision making and clinical trial designs in boys with Duchenne muscular dystrophy (DMD). Sutherland's classification has been developed 40 years ago. Ever since, the state-of-the-art medical care has improved and boys with DMD are now longer ambulatory.

Respiratory morbidity in patients with spinal muscular atrophy-a changing world in the light of disease-modifying therapies.

Respiratory complications are common in spinal muscular atrophy (SMA) and significantly contribute to morbidity and mortality in these patients. Generalized respiratory and bulbar muscle weakness translates into diverse and complex clinical consequences necessitating strict follow-up and specialized care. The natural history of SMA has evolved drastically in recent years as a result of the introduction of novel, disease-modifying therapies.

Instrumented strength assessment in typically developing children and children with a neural or neuromuscular disorder: A reliability, validity and responsiveness study.

The aim of this study was to determine the clinimetric properties, i.e., reliability, validity and responsiveness of an instrumented strength assessment in typically developing (TD) children and children with cerebral palsy (CP) and Duchenne muscular dystrophy (DMD).

Longitudinal Alterations in Gait Features in Growing Children With Duchenne Muscular Dystrophy.

Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Three-dimensional gait analysis (3DGA) could provide sensitive parameters to study the efficacy of clinical trials aiming to preserve ambulation. However, quantitative descriptions of the natural history of gait features in DMD are first required.

Clinical Variability in Spinal Muscular Atrophy Type III.

Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status.

Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models.

Muscle weakness has a limited effect on motor control of gait in Duchenne muscular dystrophy.

Aim: Our aim was to determine if synergy weights and activations are altered in Duchenne muscular dystrophy (DMD) and if these alterations could be linked to muscle weakness.

Methods: In 22 children with DMD and 22 typical developing (TD) children of a similar age, surface electromyography (sEMG) of the gluteus medius, rectus femoris (REF), medial hamstrings, tibialis anterior, and medial gastrocnemius (GAS) were recorded during gait. Muscle weakness was assessed with maximal voluntary isometric contractions (MVIC).

Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: A multi-institutional collaboration.

The timed 4-stair climb (4SC) assessment has been used to measure function in Duchenne muscular dystrophy (DMD) practice and research. We sought to identify prognostic factors for changes in 4SC, assess their consistency across data sources, and the extent to which prognostic scores could be useful in DMD clinical trial design and analysis. Data from patients with DMD in the placebo arm of a phase 3 trial (Tadalafil DMD trial) and two real-world sources (Universitaire Ziekenhuizen, Leuven, Belgium [Leuven] and Cincinnati Children's Hospital Medical Center [CCHMC]) were analyzed.

Normative data and percentile curves for the three-minute walk test and timed function tests in healthy Caucasian boys from 2.5 up to 6 years old.

The three-minute walk test (3MWT) and timed function tests (TFTs) (rise from floor, 10 m run, climbing and descending four stairs) are currently used to evaluate functional capacity in young boys with neuromuscular disorders. This study aimed to generate normative data in healthy boys aged 2.5 up to 6 years for these tests and to provide percentile curves according to age and height.

Gait deviations in Duchenne muscular dystrophy-Part 2. Statistical non-parametric mapping to analyze gait deviations in children with Duchenne muscular dystrophy.

Background: Prolonged ambulation is considered important in children with Duchenne muscular dystrophy (DMD). However, previous studies analyzing DMD gait were sensitive to false positive outcomes, caused by uncorrected multiple comparisons, regional focus bias, and inter-component covariance bias. Also, while muscle weakness is often suggested to be the main cause for the altered gait pattern in DMD, this was never verified.

Gait deviations in Duchenne muscular dystrophy-Part 1. A systematic review.

Background: Although prolonged ambulation is considered important in children with Duchenne muscular dystrophy (DMD), articles describing gait deviations in DMD are scarce.

Research Question: Therefore, our research questions were the following: 1) what are the most consistently reported spatiotemporal-, kinematic-, kinetic-, and muscle activity deviations in children with DMD in literature, 2) what is the quality of the studies describing these deviations, and 3) is there need for further research?

Methods: We conducted a systematic literature search for studies published before the end of June 2017 in six online databases. We created a data extraction form to define information on materials and methods and on the analyzed gait parameters for each paper included in the review.

Comparison of ambulatory capacity and disease progression of Duchenne muscular dystrophy subjects enrolled in the drisapersen DMD114673 study with a matched natural history cohort of subjects on daily corticosteroids.

Duchenne muscular dystrophy is a rare genetic disorder with life-limiting pathology. Drisapersen induces exon 51 skipping, thereby producing a shorter but functional dystrophin protein. The longest available data are from an open-label extension study (PRO051-02) treating 12 boys with drisapersen (6 mg/kg/week subcutaneously).

Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.

Background: Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations.

Methods: This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks.

Patterns of disease progression in type 2 and 3 SMA: Implications for clinical trials.

The aim of the study was to establish 12-month changes in the Hammersmith Functional motor scale in a large cohort of SMA patients, to identify patterns of disease progression and the effect of different variables. 268 patients were included in this multicentric study. Their age ranged between 2.

Old measures and new scores in spinal muscular atrophy patients.

Introduction: A recent Rasch analysis performed on the Hammersmith Functional Motor Scale-Expanded (HFMSE) in patients with spinal muscular atrophy (SMA) identified issues impacting scale validity, redundant items, and disordered thresholds on some items.

Methods: We modified the HMFSE scoring based on the Rasch analysis and on expert consensus to establish whether the traditional scoring overestimated the number of patients with changes within 2 points from baseline. Data were collected retrospectively from multicenter data sets in 255 type 2 and 3 SMA patients.

Six-minute walk test: reference values and prediction equation in healthy boys aged 5 to 12 years.

Objective: This study aimed to (1) generate normative data in healthy boys aged 5-12 years for the six-minute walk test (6MWT), an outcome measure currently used in clinical trials in Duchenne muscular dystrophy (DMD), (2) to describe the relation with anthropometric variables and myometry, and (3) to compare our data with published equations.

Methods: The 6MWT was conducted in 442 boys according to a standardized protocol, as currently used in clinical trials in DMD. Maximal voluntary isometric contractions for knee flexion and extension were recorded with a hand-held myometer.

Ambulatory capacity and disease progression as measured by the 6-minute-walk-distance in Duchenne muscular dystrophy subjects on daily corticosteroids.

In order to understand contemporary natural history of Duchenne muscular dystrophy (DMD), we report 6-minute walk distance (6MWD) and its change over time from a large single centre population of corticosteroid treated DMD boys. Sixty-five boys on daily corticosteroid treatment were identified with a mean (SD) age of 9.5 (2.

Test-retest reliability and developmental evolution of the 6-min walk test in Caucasian boys aged 5-12 years.

The 6-min walk test (6MWT) assesses functional capacity and has been used as outcome measure in therapeutic studies in childhood neuromuscular disorders. The objectives were to evaluate test-retest reliability of the 6MWT and to generate normative data for healthy boys aged 5-12 years. Ninety boys (mean age 8 years 10 months) were recruited over four age subcategories (5-6, 7-8, 9-10, 11-12 years).

Effects of glucocorticoids and idebenone on respiratory function in patients with duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD) progressive weakness of respiratory muscles leads to a restrictive pulmonary syndrome that contributes to early morbidity and mortality. Currently no curative treatment exists for DMD. In a Phase II randomized placebo-controlled study (DELPHI) in 21 DMD boys at age 8-16 years, idebenone (450 mg/d) showed trends of efficacy for cardiac and respiratory endpoints.

Gait assessment in children with duchenne muscular dystrophy during long-distance walking.

The aim of this study was to investigate the alteration of the gait pattern in 25 children with Duchenne muscular dystrophy, using body-worn inertial sensors during a long walking distance. Normalized spatiotemporal gait parameters and their variability were extracted from the angular velocity of the shanks; the smoothness of the trunk movement was assessed based on the spectral entropy of the acceleration norm. As compared to healthy children, patients with Duchenne muscular dystrophy showed significantly lower stride velocity and a less smooth trunk movement.

Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial.

Early mortality in Duchenne muscular dystrophy (DMD) is related to cardiac and respiratory complications. A phase IIa double-blind randomized placebo-controlled clinical trial was conducted to investigate the tolerability and efficacy of idebenone therapy in children with DMD. Twenty-one DMD patients (aged 8-16 years) were randomly assigned to daily treatment with 450 mg idebenone (Catena®) (n=13) or placebo (n=8) for 12 months.

CINRG pilot trial of oxatomide in steroid-naïve Duchenne muscular dystrophy.

The authors report a pilot open-label two-center therapeutic trial of oxatomide in 14 steroid-naive DMD boys aged 5-10 years. Comparison of linear evolutions between 3 months medication-free lead-in periods and 6 months treatment periods showed no significant differences in quantitative (QMT) and manual (MMT) measurements of muscle strength and timed functional tests. A modest mitigation of strength deterioration over time cannot be excluded.