Dissertation Abstract

Measurement of Disease in Multiple Sclerosis: Research and Clinical Applications

Evaluating "disease" and response to treatment in multiple sclerosis rests upon appropriate selection of disease measures. Unlike most chronic neurological conditions, multiple sclerosis (MS) is now considered treatable. As we embark upon new classes of agents, combinations of therapies and more aggressive treatments identification of the appropriate disease measures has never been more important.

A review of outcome measures in MS discussing the history of current and emerging measures are presented. Issues in the use of these measurements are also discussed. Use of a traditional clinical measure the Kurtzke EDSS (Kurtzke, 1983) and components of the newer less established Multiple Sclerosis Functional Composite (MSFC) (Fischer, et al, 1999), are presented in the context of a proposal for a treatment trial.

Outcome data are presented from a 2-year study of MS patients at baseline and following autologous haematopoietic stem cell transplantation (AHSCT). Results indicate increasing disability and functional decline in the absence of new lesions on MRI and declining inflammatory markers in cerebral spinal fluid. The findings suggest a process contributing to clinical worsening not evident with conventional MRI measures.

Further investigation of a possible explanation for worsening in functional/disability measures in the same patients was done. The hypothesis was that functional worsening is related to increasing brain atrophy. Longitudinal volume measures of specific areas of the brain and functional measures are presented and discussed. Findings in this study suggest that atrophy measures are more specific, sensitive and better reflect functional decline. In particular corpus callosal (CC) volumes were found to exhibit significant change in MS patients before and following AHSCT. CC volume may be a more consistent and reliable monitor of atrophy. Since extensive axons transverse this area, CC volume may also be more representative of the generalized disease process. In addition CC volume is relatively simple to apply and could be useful in a clinical setting.

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