Tao_whole_thesis_ex_pub_mat.pdf (6.51 MB)
Associations between environmental or behavioural factors and natural history of MS
thesisposted on 2023-05-28, 09:50 authored by Tao, C
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¬¨‚àû 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.
Rights statementCopyright 2018 the author Chapter 3 appears to be the equivalent of a pre-print version of an article published as: Tao, C., Simpson Jr, S., Taylor, B. V., van der Mei, I. 2017 Association between human herpesvirus & human endogenous retrovirus and MS onset & progression, Journal of the neurological sciences, 372, 239-249 Chapter 4 appears to be the equivalent of a pre-print version of an article published as: Tao, C., Simpson Jr., S., van der Mei, I., et al. 2016. Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis, Journal of neurology, neurosurgery, and psychiatry, 87(12), 1343-1349 Chapter 5 appears to be the equivalent of a pre-print version of an article published as: Tao, C., Simpson Jr., S., Taylor, B. V., Blizzard, L., Lucas, R. M., Ponsonby, A.-L., Broadly, S., AusLong/Ausimmune Investigators Group, van der Mei, I., et al., 2018. Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset, Frontiers in neurology, 9, 418. Copyright Copyright 2018 the authors. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.