October 10, 2003
Amit Bar-Or, M.D.
Neurologist and Neuroimmunologist, McGill University and the Montreal Neurological Institute
Most experts agree that several different processes are involved in producing damage to myelin in the brain of patients with MS. It is interesting to note that this demyelination in MS occurs not just in the deep 'white matter,' but also in the cortical regions of the brain, the 'gray matter'. The extent and pattern of demyelination in this part of the brain of MS patients was recently determined in studies looking at brain tissue obtained from 20 MS patients, compared to 7 patients without neurological disease (1).
In the gray matter of the cerebral cortex, 109 areas of damage were found, most of which were completely within the cortex. In fact, the percentage of areas that were demyelinated was roughly four times higher in the cerebral cortex than in the white matter. These results indicate that the cerebral cortex is likely to be a major site of MS lesions and of demyelination, and this must be taken into account when assessing the degree of demyelination in the brains of patients.
While magnetic resonance imaging (MRI) has provided us with an important tool for the diagnosis of MS, the standard MRI techniques are not capable of looking directly at the myelin in the brain. In particular, the MRI appearance of remyelinated areas—areas that are healing—is largely unknown. In a recent study, a group of researchers compared MRI findings directly with the brain tissue in MS patients (2). A researcher unaware of the MRI characteristics assessed the presence of remyelination in the tissue specimens. The investigators found that all MS lesions that are remyelinating and healing can be identified based on their MRI appearance. These findings represent an early effort at trying to identify particular features of MRI that might indicate the integrity of myelin in the involved region.
MRI studies in animal models are also being pursued in order to develop new MRI techniques that can distinguish between different types of brain injury in MS. Different types of tissue injury may have a very different impact on the long-term disability of patients. Investigators recently used a new MRI technique known as diffusion tensor imaging (DTI), which enables them to visualize the flow of water molecules in the brain (3). They realized that when myelin is lost, water flows more easily across the path of the nerve bundles. As long as the nerve bundles remain intact, water flow does not change.
DTI may become a useful approach to distinguish different types of injury to the brain. Similar advances will, in turn, enable us to monitor these parameters over time, understand whether a patient’s MS is getting worse even though they appear to be doing well, and be able to apply new therapies to the integrity of axons and myelin.
1. Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ. Subpial demyelination in the cerebral cortex of multiple sclerosis patients. Journal of Neuropathology & Experimental Neurology. 62(7):723-32, 2003.
2. Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Archives of Neurology. 60(8):1073-81, 2003.
3. Song S-K, Sun S-W, Ramsbottom MJ, Chang C, Russell J, Cross AH. Dysmyelination
revealed through MRI as increased radial (but unchanged axial) diffusion
of water. Neuroimage 17:1429-1436, 2002.
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