P120 Refining MRI pattern in sarcoglycanopathies: upper body pattern and new approaches to assess disease progression
Sarcoglycanopathies are autosomal recessive limb-girdle muscular dystrophies caused by mutations in γ, α, β, and δ sarcoglycan genes. The lower limb (LL) MRI pattern has already been reported and gives diagnostic clues. Instead, the MRI pattern of the upper body (UB) has not been described and could be valuable to understand the imaging phenotype and progression of muscle involvement in sarcog lycanopathies. To describe the UB MRI pattern in sarcoglycanopathies and its correlation with pattern of the LL, disease duration and motor status. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: L Costa Comellas, Á Sánchez-Montáñez, L. Maggi, J. Díaz-Manera, A. D'Amico, A. Pichiecchio, E. Pegoraro, M. Monforte, N. Løkken, C. Marini-Bettolo, D. Vlodavets, M. Walter, N. Voermans, S. Monges, K. Claeys, J. Bevilacqua, J. Alonso, G. Comi, C. Bru Source Type: research

P121 Long-term follow-up study of muscle MRI in myotonic dystrophy type 1: correlations with demographic and clinical characteristics
Muscle MRI is a useful biomarker of disease activity and severity in neuromuscular disorders. In the gene-therapy era, objective evaluation of natural history of progressive diseases and their correlations with clinical evolution are warranted. Herein, we report on long-term longitudinal study of muscle MRI in 29 patients affected by Myotonic Dystrophy type 1 (DM1). Twenty-nine consecutive patients with genetically confirmed DM1 were included in this prospective, longitudinal study. Each patient underwent a complete neurologic examination including Muscular Impairment Rating Scale (MIRS) and an MRI study at baseline and at...
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: L. Fionda, A. Lauletta, L. Tufano, E. Bucci, G. Antonini, M. Garibaldi Source Type: research

P122 Longitudinal Dixon Magnetic Resonance Imaging in dysferlinopathy patients can provide a powerful tool in assessing outcomes of therapeutic interventions.
In this study, we looked at a cohort of 11 patients from the JAIN COS natural history study who had been scanned at least 6 times over a 10-year period. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: I. Wilson, H. Reyngoudt, C Bolano Diaz, E. Araujo, U. Moore, H. Hilsden, J Diaz Manera, V. Straub, P. Carlier, A. Blamire Source Type: research

P123 MRI based criteria to differentiate dysferlinopathies from other genetic muscle diseases
Muscle MRI is a useful tool for the diagnosis of neuromuscular diseases as it identifies selective patterns of pathology that are characteristic of a specific diagnosis. In the case of dysferlinopathy (DYSF), we have described the muscle MRI features of 182 patients included in the Clinical Outcome Study for Dysferlinopathies (COS1). Using this data, we were able to identify eight characteristic MRI features labelled “pattern rules” based on the semi-quantitative Mercuri score that were present in nearly 90% of patients. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: C Bola ño Diaz, J. Verdu-Diaz, A. Gonzalez-Chamorro, V. Straub, J Diaz Manera Source Type: research

P124 A series of dysferlinopathy patients showing fluctuations in muscle fat fraction and contractile cross-sectional area values (cCSA) over a 3-year follow-up period
Dysferlinopathy is produced by mutations in the DYSF gene causing loss of dysferlin expression leading to progressive muscle weakness. Patients show different trajectories of muscle decline, the reasons for which are not completely understood. The Clinical Outcome Study for Dysferlinopathy (COS1) is a natural history study that followed 193 dysferlinopathy patients over 3 years. We identified 7 patients in whom the muscle MRI fat fraction (FF) from Dixon sequences showed a reduction in the leg and/or thigh at least between 2 visits. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: C Bola ño Diaz, I. Wilson, H. Borland, E Caldas de Almeida Araujo, J Diaz Manera, V. Straub Source Type: research

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