Multiple Sclerosis - Predicting The Next Attack

Abstract

MS is a complex disease characterized by a large heterogeneity in radiological and pathological findings but also in clinical disease course and treatment response. Prognostic factors are needed to. reliably counsel patients about their prognosis, differentiate between CIS/MS and other causes of the symptoms, . be able to start the appropriate treatment at the right moment in the right patient, and . gain more insight into the pathogenesis of MS (and . to try to prevent MS in some cases, knowing that the incidence of MS is increasing, probably caused by a, so far unknown, environmental factor). This thesis focuses on predictive factors in patients with CIS and relapsing-remitting MS (RRMS). In this introduction, an overview of the known prognostic factors is given, including clinical and bedside factors as well as genetics and body fluid biomarkers. First, an overview of risk factors for MS in the general population is given. Second, predictive factors for the next attack are described for patients with CIS and RRMS. For patients with CIS, the next attack is disease-defining, leading to the diagnosis of clinically definite MS (CDMS). In patients with RRMS, there is some controversy regarding the importance of relapses. Because the progressive phase of the disease (see figure 1) causes most of the long-term disability in MS patients, and this is independent of the location, severity and recovery of previous relapses, some people feel that relapses do not matter in relation to long-term disability. However, it is also known that relapses are associated with residual neurological deficit in 40-50% of cases, and that relapses early in the disease course (year 1 and 2) do seem to affect later disability. Furthermore, relapses have physical, emotional and financial consequences, and may lead to hospitalization and time away from work and home. Especially in early disease, relapses are the main cause of disability in MS patients. Because relapses are also the main target for all current MS therapies, it is an important topic in MS research. Because progressive MS was not investigated in the research described in this thesis, these MS subtypes are not discussed here.