Furby, J.; (2010) Investigation of neurodegeneration and neuroprotection in secondary progressive multiple sclerosis using volumetric MRI measures. Doctoral thesis , UCL (University College London).

Abstract

Multiple sclerosis (MS) is a disabling neurological disorder that affects young people. Neuroaxonal loss is believed to be the pathological correlate of the secondary progressive phase of this disease and whilst the earlier, relapsing disease is responsive to immunomodulatory treatments, progressive disease has proved resistant. Clinical trials in progressive multiple sclerosis are problematic due the variable nature of disability progression and the insensitivity of currently available disability scales. Volumetric magnetic resonance imaging (MRI) measures of brain and spinal cord atrophy are pathologically non-specific but are likely to reflect destructive processes such as neuroaxonal loss and could be used to assess treatment efficacy in clinical trials of neuroprotective agents in MS. Presented, is work assessing MRI-based atrophy measurements of various regions within the central neuroaxis in secondary progressive MS, in particular assessing their attributes for use as surrogate markers. The clinical and MRI data were acquired as part of a phase II trial of a putative neuroprotective agent, lamotrigine, in subjects with secondary progressive MS, and the treatment effect of this agent on the volumetric MRI measures is also presented. Overall measures of whole brain, grey matter and spinal cord atrophy demonstrated robust correlations with disability, both in cross-sectional and longitudinal analyses. Grey matter and spinal cord volumes were subject to high rates of change. In contrast white matter atrophy was variable and on average did not change significantly over the 2 year follow-up. Of interest was that grey matter volume was highly correlated with T1 hypointense lesion load in the white matter suggesting a possible causative link. No significant beneficial treatment effect of lamotrigine was demonstrated using any of the MRI measures. However, an early “pseudoatrophy” was observed within the white matter compartment in the treatment group suggesting an anti-inflammatory or osmotic effect.

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