The utility of ocular motor assessment in patients with a clinically isolated syndrome suggestive of multiple sclerosis
thesisposted on 27.02.2017, 02:37 by Clough, Meaghan
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised pathologically by areas of demyelination, t-cell predominant perivascular inflammation, and axonal degeneration. Approximately 85% of patients with MS initially present with a clinically isolated syndrome (CIS), which manifests as an acute or subacute episode consistent with white-matter lesion(s) in eloquent areas of the central nervous system. At present there is little understanding of either the pathological processes or the consequential functional capacity occurring at CIS. Preliminary evidence suggests that cognitive changes are present at CIS, potentially predate overt clinical symptoms, and represent an early marker of disease processes in MS. However, these deficits are often subtle and largely subclinical, with widely used measures lacking sufficient precision to elucidate changes informatively. As such, there is a clinical and research imperative to identify alternate measures that can sensitively characterise deficit. Ocular motor (OM) assessment provides an opportunity to measure a range of cognitive processes within the context of a system with a stereotyped output. This system is highly ramified and sensitive to the detection of subtle and diffuse pathological changes to the functionality of cognitive networks, and which are consequential of discrete isolated pathology (lesions) and/or (micro)structural changes, all of which occur in CIS. Previous work in patients with a confirmed diagnosis of MS has demonstrated the utility of OM assessment in these individuals, by characterising a range of deficits not demonstrable using standard clinical assessments. This thesis therefore aimed to determine the utility of OM assessment in measuring cognitive deficit in patients with CIS, both at presentation (visit 1) and over time (one year post visit 1). Given the subtlety of deficit at CIS, a range of cognitively challenging tasks were created, which place increased demands on specific cognitive domains demonstrated to be implicated in clinically definite MS (CDMS); specifically, inhibition, working memory, executive control. For all tasks, CIS patients performed significantly more poorly than neurologically healthy individuals, with deficits reflecting disruption to inhibitory control (Chapter 3) working memory (maintenance: Chapter 4), and executive control processes (cognitive flexibility and top down control: Chapter 5). Further, results suggested that inhibitory control deficits might be consequential of deficits in working memory, affecting the efficiency of top down control mechanisms (Chapter 6). Lastly, longitudinal assessment of inhibitory control demonstrated functional change both within and between patients, with a cluster of deficits appearing to predict the likelihood of conversion to CDMS. Significantly, standard neuropsychological assessment failed to demonstrate similar sensitivity both as an assessment of functional change over time, as well as a discrete measure at visit 1. Overall, results highlight the utility of OM assessment in CIS, affording the sensitive and informative characterisation of cognitive deficits in these patients. Due to the simple and quick nature of assessment, and the robust results found herein, it is proposed that OM assessment might be a clinically viable means of measuring deficit and of monitoring progression from CIS to CDMS.