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

• Published in: Neuromuscular disorders : NMD Vol. 33; p. S78
• Main Authors: Diaz, C Bolaño, Wilson, I., Borland, H., de Almeida Araujo, E Caldas, Manera, J Diaz, Straub, V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2023
• DOI: 10.1016/j.nmd.2023.07.059
• EISSN: 1873-2364
• ISSN: 0960-8966

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. Here, we describe this series of cases.
We scanned patients once every year. To reduce variability between scans, the Dixon images were assessed longitudinally by measuring the subcutaneous fat, if this was steady and above 90% across them, we considered it a true result. Six patients were female, median age 36 years (R 29-50) and median disease duration 15 years (R 11-22). Four were non-ambulant. The decrease in FF was seen in 6 patients over a 1-year period and in 1 patient over a 3-year period in lower legs (LL). Median decrease in thigh FF was -0.78% (R -9.29 – -0.14) and -8.58% (R -11.75 – -1.85) in LL. Median cCSA decreased in thighs (-8.8cm2, R -70.7 – 270.5) and increased in LL (52.5cm2, R 2.2 – 95), whereas median fat mass decreased in both segments (thigh -14.3cm2, R -173.6 – 30.3; LL -43.3cm2, R -84.8 – 61.4). There were no correlations between changes in FF and in NSAD, MMT or BMI, that were otherwise stable. Four patients reported an increase in physical activity and 2 had miscarriages. Two patients started taking multivitamins, 1 protein supplements and 1 stopped receiving hormone replacement therapy. Only one patient, by the end of study, had lower levels on FF in both thigh and LL compared to baseline. Here, we report fluctuations in FF, cCSA and fat mass over time in dysferlinopathy patients. We think that these observations are important to be aware of, as they could influence results in interventional clinical studies.