title: Associations between environmental or behavioural factors and natural history of MS
Creators: name: Tao, C
Publisher: name: University of Tasmania
Year: 2018

description: The aetiology of multiple sclerosis (MS) is unclear, but an aberrant immune response to Epstein-Barr virus (EBV) and infectious mononucleosis,a history of tobacco smoking, insufficient exposure to ultraviolet radiation, or decreased levels of 25-hydroxy vitamin D [25(OH)D] contribute to the onset in genetically susceptible individuals. Other factors such as human herpesvirus 6 (HHV6) infection, stressful life events (SLEs), number of offspring, and marijuana use may be associated with MS onset, but the evidence is currently less consistent. The effects of these factors on the age of symptom onset (ASO) and clinical course of patients with MS are also still uncertain. This thesis used three databases to investigate the roles of these established/potential risk factors in ASO and the clinical course of MS. MSBase (chapter 4) is an international neurologist database, which I used to assess whether a latitudinal gradient of ASO exists in MS patients. The Ausimmune study (chapter 5) is a population-based incident case-control study conducted in four different locations in eastern Australia that I used to assess whether environmental/behavioural factors could influence the ASO in MS patients. The AusLong study (chapters 6 and 7) is a prospective cohort study that followed cases in the Ausimmune Study for at least 5 years; I used the latter to assess whether HHV6/EBV infection and SLEs could influence MS clinical course. Within MSBase, including 22,162 patients from 21 countries, I found an inverse association between latitude and ASO, such that each 10° of increased latitude was associated with a 0.8-year earlier onset. Variation of ultraviolet radiation may play an important role in this latitudinal gradient. Using the Ausimmune Study, I showed that higher offspring number, a history of tobacco smoking, cerebral dysfunction at their first clinical diagnosis of CNS demyelination (FCD), and a primary progressive MS (PPMS) onset type were associated with a later onset, whereas a history of marijuana use was associated with an earlier onset. Both of these analyses supported the effects of modifiable factors on the age of symptom onset in MS, which may help improve surveillance and diagnostic efforts, as well as aid in planning for future case load. Using the AusLong Study, I found little evidence supporting associations between immune response to EBV/HHV6 and MS clinical course, indicating that the viral infection repertoire detected at baseline could not predict the subsequent disease course or prognosis of MS. However, using this study I found a protective effect of perceived positive SLEs on MS disease activity, such that preceding perceived positive SLEs (number, severity, and duration) were associated with a decreased hazard of subsequent conversion to MS or relapses. These results support the important role of maintaining a positive psychological well-being in reduction of the frequency of disease activity. The findings of the significant associations between environmental/behavioural factors and age of symptom onset and disease activity of MS, if replicated in other studies, will be useful for the prediction of MS onset and prognosis.