Advanced therapeutical approaches in neuromuscular disorders: the role of innovative outcome measures in rare diseases (evaluation scales, imaging, biomarkers)

The advances in the multidisciplinary care and the approval of disease-modifying therapies (DMTs) have changed the natural history of spinal muscular atrophy (SMA). There is raising evidence of newly emerging phenotypes, and my PhD project focused on two under-investigated aspects: 1) the communication abilities of long-surviving children with SMA type 1; 2) the trajectories of secondary outcomes of spinal surgery in children with SMA type 2 and 3. Methods: 1) Scoping review on brain involvement, cognition, and language in SMA1 followed by a cross-sectional study testing the MacArthur-Bates Communicative Development Inventory and the Social Communication Questionnaire as screening tools for expressive language and social communication in 41 treated SMA1 children. 2) 12 years-long retrospective study and survey for parents/caregivers and patients collecting data on postsurgical changes in respiratory function, motor function, weight, pain, and satisfaction in 32 untreated SMA2 and SMA3 children. Results: 1) In the study, 86% of patients acquired verbal skills, although with scores below normal ranges; 11% scored above the threshold for social communication difficulties suggesting the need of further investigations for autism spectrum disorders. 2) The study showed a positive impact of scoliosis surgery on respiratory function and overall satisfaction with posture and physical appearance but a negative impact on motor function, weight, pain, mobility, and care needs. Additions to the current state of the art: These results highlight the importance of large prospective studies to better interpret the impact of DMTs on communication development and scoliosis management in SMA.