EXPLORING THE INTERACTION BETWEEN FOCAL INFLAMMATION AND AXONAL INJURY IN MULTIPLE SCELROSIS: A NEW MECHANISM-DRIVEN FRAMEWORK TO MONITOR DISEASE ACTIVITY AND PROGRESSION

Despite significant progress in comprehending the pathophysiology of multiple sclerosis (MS) and the availability of treatments to prevent relapses, the challenges of halting and reversing disease progression persist. In this context, methods to identify and quantify mechanisms of injury at the patient level in a minimally invasive manner and integrate the relevant measures into both clinical trials and everyday clinical practice are warranted. With the present PhD project, we conducted different and independent studies combining clinical-radiological-serum biomarker, which involved individuals with diverse rates of disease progression, irrespective of relapses and active lesions on MRI, to deepen our knowledge into mechanisms potentially involved tissue damage and disease-related clinical course over time. Overall, our findings support the concepts that (i) coagulation activation at the level of BBB and neurovascular unit might induce and sustain inflammatory processes underlying the pathophysiology of MS, and that (ii) microstructural injury of the subventricular zone - occurring in the context of a diffuse brain tissue damage which characterize MS progression and patients’ aging - reflects a loss of multipotent neural stem cells’ neurogenic and neuroprotective functions, possibly contributing to disease progression. In parallel, the results of our longitudinal, prospective, and real-life studies - correlating imaging and other paraclinical tools with clinical outcomes - underline the importance of early treatment commencement in order to prevent disease activity and disability accrual, and support the use of OCT as a biomarker to capture both inflammatory and neurodegenerative phenomena occurring within the CNS.