Evangelos Katsarogiannis: Multiple Sclerosis: A Comprehensive Journey from Oligoclonal Bands to Cutting-Edge MRI Techniques

Abstract

Background:Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system characterized by heterogeneous clinical courses and overlapping inflammatory and vascular mechanisms. Over the turn of the past two decades, there have been substantial advances made in diagnostic criteria and therapies for patients suffering from MS. However, misdiagnosis, incomplete biomarkers, and limited quantitative monitoring remain major challenges. This thesis aims to refine diagnostic precision, assess treatment-related neural recovery, and explore advanced MRI methods for characterizing myelin pathology.

Methods:Study I reviewed all oligoclonal band (OCB)–negative cases in the Swedish MS Registry within the Uppsala region. Clinical charts, MRI scans, and cerebrospinal fluid data were re-evaluated to verify true MS and identify misdiagnoses.Study II prospectively assessed patients with relapsing–remitting MS undergoing autologous hematopoietic stem cell transplantation (AHSCT). Clinical disability (EDSS, MSIS-29) and multimodal evoked potentials (VEP, SEP, MEP) were recorded at baseline and during follow-up to quantify functional recovery.Study III longitudinally applied the Rapid Estimation of Myelin for Diagnostic Imaging (REMyDI) protocol in patients treated with rituximab or AHSCT. Whole-brain and regional myelin and volumetric values were analyzed using mixed-effects models.Study IV compared quantitative Synthetic MRI (SyMRI) parameters between MS and ischemic-stroke cohorts to differentiate demyelinating from vascular white-matter lesions and to examine normal-appearing white matter (NAWM) integrity.

Results:In Study I, one-third of OCB-negative cases were reclassified as non-MS disorders, underscoring the need for cautious interpretation of negative CSF findings. In Study II, AHSCT induced significant improvements in sensory and motor nerve conduction, paralleling clinical improvements and suggesting partial remyelination. In Study III, REMyDI detected treatment-related myelin increases, particularly following rituximab, while AHSCT showed more variable effects, reflecting different disease stages. In Study IV, SyMRI parameters distinguished typical MS lesions from vascular ones and revealed subtle NAWM abnormalities when age was controlled for.

Conclusions:Across complementary methodologies, these studies demonstrate that combining refined immunological, electrophysiological, and quantitative MRI approaches enhances both the diagnostic as well as the pathophysiological understanding of MS. Utilizing such a combined approach could ultimately improve individualized care and follow-up procedures in patients with MS.