Abdel-Mannan, Omar; (2025) Imaging Biomarkers in Paediatric Acquired Demyelinating Syndromes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The overall aim of this thesis is to improve understanding of paediatric multiple sclerosis (MS) and other acquired demyelinating syndromes (ADS) through epidemiological, clinical, and imaging studies. I investigated how clinical and radiological data can: (i) determine the long-term outcomes and incidence of ADS phenotypes in children, (ii) evaluate the real-world effectiveness of disease-modifying therapies (DMTs) in paediatric MS, and (iii) differentiate between paediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and MS to improve diagnostic accuracy and treatment decision-making. Paediatric ADS represent a spectrum of heterogeneous disorders affecting the central nervous system, with paediatric MS, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and MOGAD being the most defined forms. While clinical and paraclinical investigations are key in diagnosing children suspected of having MS, differentiation among disease phenotypes remains challenging due to overlapping features. This distinction is crucial because treatment strategies differ significantly, influencing both short- and long-term outcomes. I first used long-term follow-up data from a UK-wide prospective surveillance study to determine the incidence and outcomes of ADS in children. To address the evolving MS treatment landscape, I then conducted a large-scale, multicentre retrospective study evaluating the real-world effectiveness of newer DMTs versus injectables in paediatric MS. This provided key insights into treatment efficacy, relapse reduction, and its impact on clinical and radiological outcomes. I prospectively investigated the efficacy and safety of ocrelizumab, a newer monoclonal antibody, in paediatric MS within a real-world setting, contributing to understanding high-efficacy therapies in disease management and long-term safety. Finally, using multicentre retrospective MS and MOGAD cohorts, I identified lesion dynamics distinguishing the two diseases and explored MRI biomarkers for disease monitoring, prognostic assessment, and treatment response evaluation. These studies collectively aim to enhance our ability to diagnose and manage paediatric demyelinating disorders effectively, inform treatment decisions, and improve long-term neurological outcomes for affected children.

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