Markers of Secondary Progression in Multiple Sclerosis

Abstract

Introduction: There is no accepted definition of Secondary Progressive Multiple Sclerosis (SPMS) or set of unambiguous clinical, radiological, or other criteria that can accurately identify patients who transition to SPMS. Thus, the SPMS diagnosis is almost always a retrospective and frequently delayed process. Objective: The aim of this study was to elucidate the current understanding of phenotypic changes throughout MS course and provide insights into the detection of SPMS from the available literature on this diagnostic landscape. Methods: Comprehensive literature review aiming at detecting the transition from RRMS to SPMS. A search for relevant publications was conducted across different databases, scrutinizing studies that investigated tools and biomarkers for an accurate diagnosis of SPMS. Results: Studies from the past two decades were included. The EDSS-plus was shown to be more sensitive than the EDSS alone in identifying disability progression. Older age at onset, spinal cord lesions, higher EDSS and cerebellar dysfunction at baseline correlate with earlier transition to SPMS. We found some helpful indicators for diagnosing SPMS, including cognitive impairment, particularly on working memory, information processing speed, and verbal fluency; presence of slowly expanding lesions on MRI; thinning of retinal layers on OCT. Also, glial markers as Glial Fibrillary Acidic Protein and Chitinase-3-like protein 1 might be more suitable to identify the conversion to progressive disease than Neurofilament light chain. Certain subjective symptoms seem to be more prevalent in the SPMS phase, although further studies are needed to understand whether patient reported outcomes' measures (PROMs) and which ones could be useful in detecting the transition to a progressive phenotype. Conclusion: Our review highlights the emergence of useful biomarkers in early detection of progression of MS, such as cognitive impairment, MRI, and glial markers. We are getting closer to revolutionising the SPMS diagnosis and clinical management as we get a deeper understanding of these biomarkers.