Lesion distribution and excitability in peripheral nerve axons in multiple sclerosis

Abstract

In this thesis, a group of patients with multiple sclerosis who had heterogeneous lesion topography were studied using the technique of nerve excitability. Previously, Ng et al. (2008, 2013) found different changes in the excitability of motor and sensory peripheral axons in multiple sclerosis. The question then arose as to why these peripheral nerve abnormalities were present in the first place. At the same time, peripheral nerve abnormalities had also been detected in other central nervous system diseases such as stroke (Jankelowitz et al., 2007a; Huynh et al., 2013) and spinal cord injury (Lin et al., 2007; Boland et al., 2011). Twenty-four patients with multiple sclerosis were studied, consisting of three groups of patients divided based on where their lesions were predominantly located in the central nervous system: Brain, Spinal Cord and Mixed (brain and spinal cord group). The aim of this thesis was to firstly, reproduce the findings by Ng et al. (2008, 2013), and secondly, determine whether peripheral nerve excitability changes that were identified previously were due to the disease process itself (i.e. systemic inflammation) or due to lesion topography (i.e. downstream effect from the central nervous system) by comparing the findings of each group with the findings from those with stroke and spinal cord injury. The results were unexpected. The motor and sensory studies in this thesis did not reproduce the excitability findings reported by Ng et al. (2008, 2013) and there were no differences between subgroups, excluding topography of lesions as a major factor. In fact, nerve excitability results in patients with multiple sclerosis were found to be like those in healthy subjects. Reasons for the differences may be due to the current studied patient cohort having less severe disease with a higher proportion on arguably stronger immunomodulatory therapies. Future studies could be directed pursuing changes found by Ng et al. in larger and differently constituted subgroups of multiple sclerosis, perhaps dividing by patients by disability or by clinical phenotypes.