Magnetic resonance imaging markers of long term disability in relapse-onset multiple sclerosis patients

The aim of this thesis is to assess the ever challenging role of MRI in predicting disability in relapse-onset Multiple Sclerosis (MS) patients. It consists of four parts. In part one a brief overview of MS is given, looking at the most up-to-date knowledge on aetiology, pathogenesis, most common clinical presentations and the evolution in diagnostic process, prognosis and ever increasing treatment options for MS patients. Then, a brief review of the basic physics concepts and the techniques used to assess disability in MS is given using both conventional and non-conventional MRI. In part two, the relationship of T2 white matter lesion volume (T2WMLV) with long-term disability is assessed in a unique cohort of MS patients seen from the disease onset with a clinically isolated syndrome and followed up with clinical and MRI data every 5 years up to 20 years. In part three, using cross-sectional data from the same cohort of patients, the role of tissue specific i.e. grey matter and white matter changes in predicting disability at 20 years is assessed, using both atrophy measurements and magnetisation transfer ratio. Comparisons between sub-group of MS patients and controls are also assessed. Furthermore, the relationship of longitudinal T2WMLV changes with atrophy measurements at 20 years is also explored. In the fourth and final part of this thesis, a summary of the main findings of this work is given and there is discussion on what the future holds for the role of imaging in predicting disability in MS

Do Early Relapses Predict the Risk of Long-Term Relapsing Disease in an Adult and Paediatric Cohort with MOGAD?

OBJECTIVE: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer-term relapse risk is unknown. Here, we investigate whether early relapses increase longer-term relapse risk in patients with MOGAD. METHODS: A retrospective analysis of 289 adult- and pediatric-onset patients with MOGAD followed for at least 2 years in 6 specialized referral centers. "Early relapses" were defined as attacks within the first 12 months from onset, with "very early relapses" defined within 30 to 90 days from onset and "delayed early relapses" defined within 90 to 365 days. "Long-term relapses" were defined as relapses beyond 12 months. Cox regression modeling and Kaplan-Meier survival analysis were used to estimate the long-term relapse risk and rate. RESULTS: Sixty-seven patients (23.2%) had early relapses with a median number of 1 event. Univariate analysis revealed an elevated risk for long-term relapses if any "early relapses" were present (hazard ratio [HR] = 2.11, p < 0.001), whether occurring during the first 3 months (HR = 2.70, p < 0.001) or the remaining 9 months (HR = 1.88, p = 0.001), with similar results yielded in the multivariate analysis. In children with onset below aged 12 years, only delayed early relapses were associated with an increased risk of long-term relapses (HR = 2.64, p = 0.026). INTERPRETATION: The presence of very early relapses and delayed early relapses within 12 months of onset in patients with MOGAD increases the risk of long-term relapsing disease, whereas a relapse within 90 days appears not to indicate a chronic inflammatory process in young pediatric-onset disease. ANN NEUROL 2023

Advances in imaging to support the development of novel therapies for multiple sclerosis.

Multiple sclerosis (MS) is a common neurological disease in North America and Europe. Although most patients develop major locomotor disability over the course of 15-20 years, in approximately one-third of patients the long-term course is favorable, with minimal disability. Although current disease-modifying treatments reduce the relapse rate, their long-term effects are uncertain. MS treatment trials are challenging because of the variable clinical course and typically slow evolution of the disease. Magnetic resonance imaging (MRI) is sensitive in monitoring MS pathology and facilitates evaluation of potential new treatments. MRI measurements of lesion activity have identified new immunomodulatory treatments for preventing relapse. Quantitative measurements of tissue volume and structural integrity, capable of detecting neuroprotection and repair, should facilitate new treatments designed to prevent irreversible disability. Higher-field MR scanners and new positron emission tomography (PET) radioligands are providing new insights into cellular and pathophysiological abnormalities, and should be valuable in future therapeutic trials. Retinal axonal loss measured using optical coherence tomography (OCT) can assess acute neuroprotection in optic neuritis