Beyond muscle: a multidisciplinary approach to the involvement of the Central Nervous System in neuromuscular diseases

This PhD project focused on the neuropsychological profile of pediatric patients with Duchenne Muscular Dystrophy and the implementation of technological devices in their rehabilitation. In this disease it is known the relationship between dystrophin deficiency and neurodevelopmental disorders and neuropsychological impairments, which are frequent but often overshadowed by the more apparent motor disabilities. With the advent of novel treatments there is an even more urgent need to address the cognitive and neuropsychological manifestations of the disease. The primary goal of the project was to address some of the unmet needs in DMD by further describing the CNS-related phenotype (particularly exploring unexplored domains like social cognition), contributing to the development of a standardized toolkit for neuropsychological assessment, and investigating the potential of integrating technology into rehabilitation. The introductory Chapter 1 summarizes the main evidence from the current literature about the CNS-related phenotype of DMD, some of the currently unmet needs, and the possible role of technologies applied to rehabilitation of this pathology. Chapter 2 focused on the clinical assessment of social cognition, one of the less explored domains of the neuropsychological phenotype of DMD patients, even if potentially linked to the expression profile of the isoforms of dystrophin. The chapter includes a scoping review that provides an overview of the standardized tools previously adopted and described in the literature for the neuropsychological assessment of DMD patients, the application of an innovative clinical protocol including the assessment of social cognition, and a specific experimental setting based on implicit cognition and subliminal priming developed to further explore the social cognition deficit and its possible neural substrate. Chapter 3 is dedicated to the challenges of implementing technologies in the rehabilitation of pediatric neuropsychiatric disorders, in general, and neuromuscular disorders, in particular. It includes a comprehensive overview of the multifaceted landscape of technologies applied to the rehabilitation of pediatric neurological and neurodevelopmental diseases, in particular their implementation to telerehabilitation. Furthermore, starting from this background, the chapter address the issue of the innovative multi-modal technological interventions with the report of a case series and a clinical protocol, both based on technological devices applied to the rehabilitation of DMD patients. This doctoral project contributed to the study of the wide spectrum of neuropsychological manifestations of DMD. Our results provide preliminary evidence of a possible involvement of social cognition skills, in particular in emotion recognition. Defining the neuropsychological profile of DMD patients in detail is critical for improving their rehabilitative care and providing tailored support for their academic and daily life goals. Furthermore, some of the studies included in this project explored another area with great potential for enhancing care in DMD: the integration of technological devices and telerehabilitation. The adoption of advanced technologies and multidomain interventions have the potential to revolutionize the neurodevelopmental rehabilitation by creating immersive, adaptive, and engaging therapeutic environments. By testing the potential of these technologies, this project represented a pilot-experience of more effective interventions that are tailored to the unique challenges faced by DMD patients, enhancing their overall quality of life and long-term outcomes.