After decades of searching in vain for a single cause--and cure--for multiple sclerosis (MS), many researchers have become convinced that the disorder has many different causes and may in fact be several different diseases.
This impression is strengthened by a report in this month's Annals of Neurology, the scientific journal of the American Neurological Association, which finds that MS cases can be divided into four broad categories, two that resemble autoimmune diseases and two in which viruses or toxins may be to blame.
Among the important consequences of this proposed subdivision of the disorder, said senior author Hans Lassmann, MD, of the University of Vienna in Austria, is that treatments that may aid one patient could be harmful to another. "Besides the current anti-inflammatory and immunomodulating treatments, therapies must be tailored towards the needs of specific patient subgroups," said Lassmann.
The great benefit of the study, writes Samuel K. Ludwin, MD, of Queens University in Kingston, Ontario, in an accompanying editorial, is that the researchers were able to look at a large number of fresh injuries (or lesions) rather than having to settle for studying the scarred nervous system tissues typically seen at autopsy. They were also able to compare some of these cases to experimental models of the disease with known causes and course.
Multiple sclerosis is a disorder of the nerve fibers of the brain and spinal cord. In MS patients, scarring (sclerosis) replaces myelin, a substance that normally insulates the nerves and speeds electrical conduction through the nerves. Depending on which nerve fibers are hindered, patients can experience problems ranging from weakness and clumsiness to numbness, visual disturbances, and even emotional and intellectual changes
Some patients experience MS as cycles of relapse and remission; others progress to severe debilitation and may die from the disease.
"It is generally understood that the study of the acute lesion in MS will be of greater help to researchers than the very old, burned out lesions seen typically at autopsy," said Ludwin. "The current study is unique in the quantity of these acute cases that they have managed to assemble."
Lassmann and his collaborators, including Claudia Lucchinetti, MD, from Mayo Clinic in Rochester, Minnesota, and Wolfgang Bruck, MD, from the University of Gottingen in Germany, pooled and analyzed the relatively rare tissue samples they had collected from people suffering acute flare-ups of multiple sclerosis symptoms. These samples came from 51 patients who had brain biopsies performed to exclude other diseases and 32 patients who died in the midst of flare-ups of the disease.
"In this material we were able to define four distinctly different patterns of demyelination, suggesting profound differences in the pathogenesis of the lesions between different patient subgroups," said Lassmann.
In the short term, said Lassmann, one goal will be to define clinical and radiological criteria for these pathological groupings so that physicians can assign patients to different groups without having to resort to brain biopsies. This upcoming study, funded by the National Multiple Sclerosis Society, is being directed by Luchinetti.
In the longer term, said Ludwin, "These patients may help to determine if there are different responses to therapy between the groups, or whether different therapeutic modalities should be designed for patients within each individual group."
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