24 October, 2003
Professor David Miller
NMR Research Unit
Department of Neuroinflammation
Institute of Neurology
It is very difficult to perform reliable treatment trials in MS, when the aim is to stabilise the condition, i.e. to prevent further relapses or the development of permanent symptoms or disability. The difficulty arises because MS is so variable from one person to another, and also changes in symptoms occur generally over a very long period of time, years or even decades. For this reason, clinical trials are a major and expensive undertaking, involving large numbers of people with MS from many centres around the world, and needing at least 2 years of follow-up to determine whether a treatment is preventing relapses or other symptoms. Therefore, there has been a lot of interest in identifying a reliable surrogate outcome measure which can take the place of clinical monitoring. The idea of a surrogate measure is that it would be more sensitive, and allow us to determine if a treatment is effective more quickly and in a smaller number of people. Most importantly, there needs to be a certainty that if the treatment affects the surrogate outcome it would also be of benefit in preventing future symptoms in people with MS.
MRI scanning is now regularly used to measure the effects of treatments in trials of new agents, and is certainly sensitive, especially in relapsingremitting MS. A contrast agent called ‘gadolinium’ helps to show new areas of inflammation in which there is a breakdown of the normally tight blood-brain barrier. Already, quite a number of treatments have been shown to reduce the frequency with which such new MRI lesions appear in the white matter of the brain, for example Beta Interferon and Glatiramer Acetate. It is also encouraging that the decrease in new MRI lesions goes along with a decrease in relapses associated with these treatments. The main problem with this type of MRI monitoring is that it isn’t very good at predicting the future course of MS in terms of developing permanent disability. There seem to be different factors at work here in particular damage to the nerve fibres, also known as axons. Therefore other MRI measurements are being used that are thought more specific to axon damage - for example measures of tissue loss or atrophy, MR spectroscopy, and diffusion tensor imaging. There is also much interest in developing MRI techniques that detect remyelination, because this may be an important way of protecting the nerve fibres and ensuring that people with MS keep well in the long term.
My talk will discuss in more detail the different MRI techniques - current
and future - that are being or will be used to monitor inflammatory lesions,
axonal damage and protection, and remyelination.
Copyright © 2003, Multiple Sclerosis Society