Giulia Canella

Background: Natural history data are crucial for supporting clinical trial readiness in muscular dystrophies. Multisystemic and slowly progressive diseases, such as myotonic dystrophy type 1 (DM1), require significant efforts to define the different aspects of evolution across multiple systems. Methods: Our study aimed to model the progression of different functions (namely, muscular, motor, and respiratory) over more than 20 years in 3 different DM1 subtypes (congenital, childhood, and adult forms) related to disease duration. Results: We defined disease progression curves of different functions (muscular assessed through MRC scale during 565 visits, motor assessed through MFM scale during 409 visits, and respiratory assessed through spirometry and nocturnal saturation during 533 visits) in 9 congenital, 25 childhood, and 45 adult form, related to disease duration through a linear mixed model. The shape and slope of the progression curves differ across phenotypes, with some functional domains showing earlier and steeper declines. Conclusion: The progression curves confirm some clinical observations: (1) the decline of the upper limbs’ strength is more evident in the distal portion; (2) the decline of the lower limbs is due to ankle muscles; (3) the lung restriction and nocturnal oxygen desaturation parallel obesity onset. In addition, they show that the D1 sub- scale of the MFM scale is the most affected functional motor parameter, with a trend of decline similar to the ankle strength and the 6-minute walking test. Taken together, our data provide important guidance for the design of future clinical studies in DM1.

Background/Objectives: Duchenne muscular dystrophy (DMD) is often discussed in the literature with regard to physical impairments. This narrative review aims to show that living with DMD involves psychological, psychosocial, and cognitive aspects in addition to the well-known physical complications. Methods: Firstly, this review examines the main cognitive functions affecting subjects with DMD and the possible role of dystrophin gene mutations on the central nervous system. Secondly, it analyzes the comorbidity between DMD, neurodevelopmental disorders (autism spectrum disorders, attention-deficit/hyperactivity disorder, obsessive–compulsive disorder) and psychopathological traits (anxiety and/or depressive symptoms). Finally, the review addresses the relatively sparse literature investigating the positive aspects associated with the experience of DMD, like psychosocial resources, resilience, subjective well-being, positive individual and social functioning, and social support. Results: DMD has a significant impact on cognitive areas, probably due to dystrophin deficiency in the brain. The prevalence of neurodevelopmental comorbidities and psychopathological symptoms is also higher in people with DMD than in the general population. Despite these challenges, emerging studies highlight the role of psychosocial and environmental resources, including resilience and supportive social relations, in promoting a good quality of life and successful adaptation to disease progression. Conclusions: Early recognition of the above difficulties and strengths could ensure better care and promote an overall better quality of life for people with DMD and their families, physically, psychologically, and socially. Preclinical and clinical research is moving in the direction of finding new therapies, treatments, and psychosocial interventions to pursue these goals.