September 12, 2003
Amit Bar-Or, M.D.
Neurologist and Neuroimmunologist, McGill University and the Montreal Neurological Institute
With the appreciation that the activity of multiple sclerosis (MS) and the damage to the central nervous system (CNS) may occur early in some patients, increasing attention has turned to treating the initial stages of MS. But not everyone who has an initial episode of demyelination in the CNS turns out to have MS. Individuals having a single attack—also known as a ‘clinically isolated syndrome (CIS)’—face an uncertain future, since only a proportion go on to experience the recurrent attacks that characterize MS. Why some patients experience a single attack, while others have recurrent attacks (MS) is unknown.
Brain MRI has proven to be quite useful at the time of CIS, but remains imperfect. Patients who, at the time of CIS, have a normal brain MRI have only a 20% risk of having additional episodes (that is, developing MS). In contrast, patients who have a highly abnormal MRI at the time of CIS have about an 80% chance or greater of developing the additional attacks that define MS.
Still, 20% is a considerable number of patients with a normal-appearing MRI at the time of their CIS who may still have MS. It would be important to identify them early, in order to discuss treatment options. Furthermore, some patients with an abnormal brain MRI at the time of their CIS may turn out not to have MS, and it would be a mistake to make such a diagnosis and initiate therapy that may not help and, possibly, could even harm them. So while MRI is very helpful early on in terms of trying to diagnose and plan treatment, it is still not as close to perfect as one would like.
There is great interest in identifying additional, easy-to-measure and reliable tests that could be done early on and that could predict who will end up with MS and who will not, or whether individuals are likely to have a more aggressive course of MS or a milder course of MS.
In a recent New England Journal of Medicine (NEJM) study (1), Austrian researchers found that a blood test done at the time of CIS that measures the levels of two antibodies made by the immune system against particular components of myelin in the brain (known as MBP and MOG), may predict the outcome of CIS. The test was given to 103 patients with CIS. The researchers found that there was an association between the presence of these antibodies and the risk of a second clinical event (i.e., developing clinical MS). Over approximately 4.5 years of follow up, 21 of 22 patients (95%) who were positive for both MBP and MOG antibodies had a second clinical event. Only nine of 39 (23%) of patients with no antibodies detected at the time of CIS ended up developing MS. For patients with only one of the two antibodies being detected, the risk was intermediate.
If it turns out to be valid, such a blood test would be a relatively simple and very useful thing to do. It is minimally invasive and inexpensive. Theoretically, the test could be given to people when they have their first isolated syndrome and help guide the care team in terms of predicting the eventual development of MS. It could also help in terms of starting therapies early, or following patients more closely, as opposed to just waiting until they come back with another episode. This would be particularly useful if researchers could show that the combination of this blood test and a brain MRI at the time of CIS, was an even better predictor of outcome than either test alone (2).
Finally, in addition to the potential for such a test to provide valuable information about whether a person with CIS will end up with MS, it is interesting to speculate about the role of these anti-myelin antibodies in the MS process. MBP and MOG, two components of myelin, have been considered potential targets in MS for a long time. The current study does not tell us, however, whether or not these antibodies are causing damage by attacking MBP and MOG, or whether the antibodies just represent a marker of immune system activity. It is also possible that someone could have these antibodies but not have MS, or any neurological symptoms. If they turn out to be involved in causing damage to the CNS, the blood test may identify particular patients who could benefit from treatments that are directed against B cells (the immune system cells that make antibodies) or treatments that remove the potentially damaging antibodies from the circulation (2,3).
(1) Berger T, Rubner P and Schautzer F. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. New England Journal of Medicine 349:139–145, 2003.
(2) Antel JP and Bar-Or A. Do myelin antibodies predict the diagnosis of multiple sclerosis? New England Journal of Medicine 349(2):107-109;2003.
(2) Scolding N. First attack in multiple sclerosis: harbinger or history? Lancet Neurology 2(9):526, 2003
(4) Antel JP and Bar-Or A. Do myelin antibodies predict the diagnosis
of multiple sclerosis? New England Journal of Medicine. 349(2):107-109;2003.
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