Expanding Perspectives in Neuromuscular Disorders: Central Nervous System Involvement and Imaging Advances

This PhD project pursued two translational and multidisciplinary aims: investigating central nervous system (CNS) involvement in neuromuscular disorders, particularly spinal muscular atrophy (SMA), and evaluating high- and ultra-high-field MRI as a biomarker in NMDs. The advent of disease-modifying therapies has changed the natural history of SMA, improving survival while raising new clinical challenges, including the assessment of CNS involvement. The findings on cognitive, language, and behavioural outcomes in SMA, showed possible CNS involvement in SMA type I and in infants identified through newborn screening, with evidence of developmental, language, and behavioural delays. The findings also highlighted limitations of current assessment tools, prompting consideration of alternative approaches. The second part of the project focused on imaging biomarkers in NMDs and rare diseases. It explored the role of muscle MRI as a diagnostic and monitoring tool, including the use of artificial intelligence, and evaluated the feasibility of ultra-high-field muscle spectroscopy with an innovative coil. Promising results were obtained using hydrogen, phosphorus, and deuterium spectroscopy in both healthy individuals and patients with neuromuscular disorders. The project also explored novel MRI sequences and techniques through selected case series. This doctoral project advanced the study of clinical and imaging biomarkers in neuromuscular disorders (NMDs). By integrating complementary clinical and neuroradiological approaches, it highlights the complexity of NMDs and the need for multidisciplinary management. The findings support earlier and more accurate diagnosis and have important implications for the design and implementation of future clinical trials.