P125 Quantitative MRI in upper limb muscles of patients with dysferlinopathy: 6-months and 12-months longitudinal data from the natural history Jain COS 2 project
In dysferlinopathy patients, the upper limb muscles are affected in the later stages of the disease, and muscle fat replacement of arm and forearm muscles follows thigh and leg involvement. Additionally, increased disease activity (such as inflammation) in lower limb muscles has been reported to be a feature in patients with dysferlinopathy. Adding to the COS1 results, a longitudinal quantitative MRI study in upper limbs was set up in four clinical centers (UK, France, Italy, USA), investigating both muscle fat fraction (FF; reflecting the extent of muscle fat replacement) and water T2 (reflecting the extent of muscle infl...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: I. Wilson, H. Reyngoudt, E Caldas de Almeida Araujo, P. Baudin, B. Marty, C. Bolano-Diaz, J. Diaz-Manera, L. Rufibach, H. Hilsden, G. Querin, E. Pegoraro, J. Mendell, T. Stojkovic, V. Straub, A. Blamire, P. Carlier Source Type: research
P126 Muscle MRI-histology matching: data from 130 MRI-based muscle biopsies
We report on data from 130 MRI-based muscle biopsies from various conditions, aiming to elucidate the matching between muscle MRI features and histopathological findings. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. Garibaldi, L. Tufano, G. Merlonghi, A. Lauletta, L. Fionda, G. Antonini Source Type: research
P127 Fat-fraction quantification using Dixon technique in Duchenne muscular dystrophy and its correlation with clinical progression and genotypic characteristics
Fat fraction quantification using Dixon technique is a relatively novel method that can be used to accurately quantify the extent of fatty infiltration in diseased muscle. While studies have found a correlation with muscle fat fraction (MFF) with disease severity in Duchenne muscular dystrophy (DMD), the current study additionally explores its correlation with the rate of functional decline in terms of MRC sumscore, North Star Ambulatory Assessment Score (NSAA), six-minute walk test (6MWT) and also with the disease genotype. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. Mohanty, D. Menon, M. Kumar, A. Nalini, J. Saini, S. Vengalil, S. Nashi Tags: DMD - IMAGING AND OUTCOME MEASURES Source Type: research
P128 Quantitative ultrasonography reveals skeletal muscle abnormalities in female carriers of DMD pathogenic variants
The objectives were to compare lower limb NMUS findings in female carriers (FcDMD) vs non-carriers (FncDMD) of DMD pathogenic variants. Twenty-eight women (15 FcDMD and 13 FncDMD) underwent detailed clinical evaluation and NMUS. We collected information about muscle-related complaints and assessed muscle strength using the MRC scale. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M Cavalcante Fran ça, B. Loureiro, M. Brito, C. Iwabe, S. Dertkigil Source Type: research
P129 Givinostat in DMD: results of the Epidys study with particular attention to MR measures of muscle fat fraction
A randomized, double blinded, placebo controlled, multicenter Phase 3 clinical trial (Epidys; NCT02851797) examined the safety and efficacy of givinostat, an orally active histone deacetylase inhibitor in development, in ambulant boys with Duchenne muscular dystrophy (DMD). A total of 179 DMD boys aged ≥6 years at baseline were enrolled and treated for 18 months. The primary efficacy assessment was the time to climb 4 standard stairs (4SC). The primary endpoint was complemented by six key secondary efficacy endpoints: NSAA, time to rise from floor, 6MWT, knee extension and elbow flexion muscle s trength, and a biomarker ...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: K. Vandenborne, R. Willcocks, G. Walter, S. Forbes, S. Cazzaniga, P. Bettica, E. Mercuri, C. McDonald Source Type: research
P130 Two-year muscle MRI observations from a phase 1b trial of fordadistrogene movaparvovec (PF 06939926) for Duchenne muscular dystrophy (DMD)
Fordadistrogene movaparvovec (PF 06939926) is an adeno-associated virus serotype-9 (AAV9) gene-replacement construct containing a mini-dystrophin being developed for DMD, which aims to restore functional protein to muscle. Magnetic resonance imaging (MRI) is an important non-invasive tool that can be used for monitoring disease progression and can inform future functional changes. Here we present 2-yr quantitative MRI measurements from 16 ambulatory participants with a genetic diagnosis of DMD from a phase 1b, multicenter, single-arm, open-label trial (NCT03362502). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: S. Sherlock, H. Li, R. Butterfield, P. Shieh, E. Smith, T. McDonnell, K. Ryan, M. Binks Source Type: research
P131 MRI fat fraction distribution in Duchenne muscular dystrophy (DMD): effect size comparison to identify optimal biomarker for early efficacy assessment
Changes in mean MRI proton density fat fraction (MRI-PDFF) in DMD and other neuromuscular trials are assessed as a potential early biomarker of efficacy. However, mean MRI-PDFF within the muscle region of interest (ROI) may not reflect pathologically relevant changes in the distribution of fatty infiltration with disease modifying treatments. We hypothesized that other biomarkers indicative of changes in the distribution may have a larger effect size (Cohen's d) thereby increasing statistical power to detect efficacy if utilized in clinical trials. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: M. Hammond, J. Harris, B. Luna, F. Roche, F. Vincent, M. Berger, S. Zabbatino, R. Scheyer, S. Holland Source Type: research
P132 Quantifying skeletal muscle fat fraction and function using whole body magnetic resonance imaging (MRI) in men with Becker muscular dystrophy
Becker Muscular Dystrophy (BMD) results in impaired function of dystrophin and leads to fat replacement of skeletal muscle impacting function. There is a growing interest in drug development for BMD, and biomarkers that characterize muscle quality and their relationships to function are needed. Quantitative magnetic resonance (qMR) imaging of muscle fat fraction (FF) is highly reliable and sensitive to disease progression in muscular dystrophy. Whole-body quantitative three-point Dixon (3PD) imaging (WBI) has efficient acquisition and the ability to analyze multiple muscles to develop body segment-specific FF composites. (...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: K. Rock, R. Willcocks, S. Forbes, A. Barnard, D. Lott, B. Smith, S. Prabhakaran, W. Rooney, M. Daniels, S. Subramony, N. Chahin, G. Walter, K. Vandenborne Source Type: research
P133 Influence of X-chromosome activation pattern in muscles on symptoms and progression of cardiac and muscle symptoms signs in women with pathogenic dystrophin gene variants: a 6-year follow-up of 53 patients
Duchenne and Becker muscular dystrophies are caused by mutations of the dystrophin gene. The gene mutation causes the absence or very severe reduction of dystrophin protein in the muscle and heart cells. Female carriers who have both muscular and cardiac involvement are classified as “manifesting carriers”. However, the incidence of skeletal muscle involvement among female carriers of DMD was 2.5%–19%, and of dilated cardiomyopathy (DCM) 7.3%–16.7% for DMD carriers and 0%–13.3% for BMD carriers, but in one of the latest cross-sectional studies with some of the most sen sitive outcome measures to date, 81 % showed...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: Z. Lyu, N. Poulsen, H. Joensen, C. Lando, M. Dun ø, H. Bundgaard, N. Vejlstrup, J. Vissing Source Type: research
P134 Energetics and acid-base status of skeletal muscle at rest and following isometric dorsiflexion and plantar flexion contractions in Duchenne muscular dystrophy
In this study, we evaluated ambulatory participants with DMD (n=20, 8.7±2.0 years) and u naffected age-matched controls (n=18, 8.5±2.6 years) using a 3T Philips MR system. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: P. Awale, C. Lopez, T. Taivassalo, K. Vandenborne, G. Walter, S. Forbes Source Type: research
P135 Facilitators and barriers in living the desired adult life, despite having Duchenne muscular dystrophy (DMD)
This study explored the desired situation for adolescents and adults with Duchenne Muscular Dystrophy (DMD) concerning making their own choices during adult life. Besides, the view and role of parents in this process was explored. At last, the gap was captured between the current situation and the desired situation, with attention for the factors which are of influence on this gap. A prospective, cross-sectional survey was conducted. Topics from the survey were based on literature study, an expert meeting, and 20 interviews with adolescents and adults with DMD and their parents. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: Y. Veenhuizen, L. Merkenhof, E. Vroom, E. Cup, J. Groothuis, S. Houwen Source Type: research
P136 Using the North Star and timed function test centiles in boys with Duchenne muscular dystrophy – a prospective study
The North Star Ambulatory Assessment (NSAA) is a functional scale to assess motor function in patients with Duchenne Muscular Dystrophy (DMD) and scores ranging from 0 - 34. The two-timed function tests (TFT), 10m walk/run (Item 17 on the NSAA) and rise from floor (Item 11 on the NSAA), have been shown to be strongly correlated with the total NSAA score. However, there is significant heterogeneity in the trajectories of patients due to several factors including genetics, steroid regime, comorbidities, and differences in care. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: A. Wolfe, G. Stimpson, E. Milev, E. O'Reilly, A. Manzur, A. Sarkozy, F. Muntoni, G. Baranello Source Type: research
P137 Prophylactic use of cardiac medications and prolonged survival in Duchenne muscular dystrophy
Evidence for prolonged survival after prophylactic treatment of left ventricular dysfunction in Duchenne muscular dystrophy (DMD) is limited. We used retrospective, population-based surveillance data collected during 2004-2016 by the Muscular Dystrophy Surveillance, Tracking and Research Network to describe survival among treated and untreated individuals. We analyzed 327 males with confirmed DMD who were: 1) born during 1982-2009, 2) ≥6 years of age at last visit, and 3) started on cardiac prophylaxis before 14 years of age or did not receive prophylactic treatment. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: K. Conway, S. Thomas, E. Ciafaloni, J. Mann, P. Romitti, K. Mathews Source Type: research
P138 Development and evaluation of a composite time-to-progression endpoint that spans ambulatory and non-ambulatory stages of Duchenne muscular dystrophy (DMD)
This study developed and characterized a composite endpoint for clinically meaningful progression in DMD across three domains: ambulatory motor, upper-limb motor, and pulmonary function. Progression criteria were evaluated in each domain: A) loss of ≥ 3 NSAA total score points; B) loss of ≥ 3 PUL1.2 total score points; C) decline of FVC %-predicted [FVC%p] ≥ 10% points. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: C. McDonald, F. Muntoni, J. Marden, N. Goemans, A. Gomez-Lievano, A. Zhang, Z. Chen, S. Ward, J. Signorovitch Source Type: research
P139 Correlation and validation of the North Star Ambulatory Assessment, timed test and motor function measure centiles for boys with Duchenne muscular dystrophy
There is significant heterogeneity in the North Star Ambulatory Assessment (NSAA) trajectories of boys with DMD, which may present a challenge for clinical care and development of clinical trials. Centiles quantify the cross-sectional variability in cohorts, are easily interpretable for patients and parents, and have been described for the Motor Function Measure (MFM) in boys both on and off corticosteroids (CS). We used the NorthStar Database to develop NSAA, Rise from Floor (RFF) and 10m Walk (10MWR) centiles-for-age for boys with DMD on CS. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: E. Milev, G. Stimpson, M. van der Holst, A. Wolfe, E. O'Reilly, A. Manzur, E. Niks, S. Houwen-Opstal, G. Baranello, F. Muntoni Source Type: research
