How long is the presymptomatic phase of multiple sclerosis?

Abstract

An emerging challenge in neurodegeneration is diagnosing disease in the preclinical phase prior to onset of irreversible damage (Dubois et al., 2010). The hypothesis is that if a relatively safe disease-modifying therapy could be given, or started, early enough in the course of a neurodegenerative disease we may be able to prevent, or delay, the onset of clinical disease or at least reduce the consequences of the disease. Multiple sclerosis (MS) is not too dissimilar to other neurodegenerative diseases in this regard with evidence demonstrating a presymptomatic phase. In this context the presymptomatic phase is distinct to the prodromal phase of MS, or period of latency (Kurtzke, 2000), which refer to the so called ‘at risk’ period prior to the onset of focal inflammatory pathology that defines MS pathologically (Ramagopalan et al., 2010). Migration studies suggest the period of latency from exposure to putative causal environmental risk factors and the onset of biological disease, i.e. presymptomatic or clinical disease, is between 10 and 20 years (Kurtzke, 2000). MS prevention strategies would need to target the periods prior to, and during, the period of latency. This has practical implications in that prevention strategies may only work in the prodromal phase of the disease, prior to the onset of biological disease, or focal inflammatory pathology, and hence the distinction between a pre-disease state and a disease state is not trivial. In comparison, disease-modifying therapies could potentially target the disease after of the onset of focal MS pathology and could be given in either the presymptomatic (radiologically isolated syndrome-RIS) or symptomatic phase (clinically isolated syndrome or multiple sclerosis).