Modelling disability trajectories over the disease course in Multiple Sclerosis patients

Background: Multiple Sclerosis (MS) is a chronic autoimmune disease that attacks the CNS. The immune attack on the CNS cause the damage of a substance, called myelin, which surrounds and protects the nerve fibres. MS is one of the most common causes of neurological disability in young adults. It is well established that axonal injury is a feature of multiple sclerosis (Charcot JM, 1880), that the extent of axonal injury is correlated with the degree of inflammation (Trapp BD, 1998) at least in relapsing multiple sclerosis, and that a close association between inflammation and neurodegeneration might exist in all disease stages of multiple sclerosis (Kutzelnigg A, 2005; Frischer J, 2009). However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits remain ambiguous. Nevertheless, this point is central for understanding the mechanism of tissue injury in multiple sclerosis, which may have an effect on treatment. It has therefore been suggested that disability accrual at later MS stages is primarily driven by neurodegeneration and is largely independent of inflammation. These observations have led to a two-stage hypothesis, with the first stage representing a therapeutic window for modifying disease trajectory, which then becomes uniform in the second stage of disease (Leray E, 2010). This concept was also confirmed in others studies (Scalfari A, 2010; Stys PK, 2012).