A Quicker Predictor for MS

As with many chronic medical conditions, there is a lot of guesswork involved in making a diagnosis of multiple sclerosis (MS). Lesions in the brain and spinal cord cause a wide range of neurological symptoms, which may happen suddenly and last for hours or days. Although brain imaging is the usual method of initially diagnosing MS, a blood test might be a simpler way to identify people with the disease.

Austrian researchers found that a blood test measuring two antibodies, which are substances that the immune system produces, may be a better MS predictor. The study was published in the New England Journal of Medicine (NEJM) in 2003. Researches believe that these two antibodies may attack the myelin, a protective coating that insulates the nerves. The test was given to 103 participants who had one neurological episode, as well as brain imaging and spinal fluid tests that indicated that they had a high risk of MS. Researchers found that 95 percent of patients with both antibodies were eventually diagnosed with MS; 83 percent with one antibody were later diagnosed; and only 23 percent with neither antibodies went on to be diagnosed.

Dr. Amit Bar-Or, an assistant professor in neurology and neurosurgery at the Montreal Neurological Institute and an associate in microbiology and immunology at McGill University in Montreal, Canada, contributed to an editorial that accompanied the NEJM article. Below, Bar-Or discusses the need for a reliable MS blood test and how it might affect treatment decisions.

How is MS traditionally diagnosed?
Most patients will come to the doctors when they have their first neurological episode, which may involve a range of different symptoms or signs. This first episode is called a clinically isolated syndrome.

The part of the nervous system that is involved in an attack will determine what kind of symptoms or signs a patient has. These may include loss of vision, problems with weakness, lack coordination of the limbs, unsteadiness while walking or a loss of sensation or a tingling sensation in the limbs, trunk or face.

A segment of patients will end up having just that isolated event .However, another portion will go on to have a second episode and eventually end up with a diagnosis of multiple sclerosis. Patients are only diagnosed with MS if they had two or more neurological episodes.

What diagnostic tests are available for MS?
What has been most helpful in identifying people who will transition to an MS diagnosis is a type of brain imaging called magnetic resonance imaging (MRI). Research shows that if you look at an MRI of the brain at the time of the first episode, the presence or absence of lesions associated with demyelination, or a loss of myelin, can be helpful in predicting the likelihood of eventually having a second attack, and consequently a multiple sclerosis diagnosis.

If you have an isolated event, but your brain scan is quite normal looking, then you are at a relatively low risk of developing MS. Depending on the study, the risk may be as low as 10 percent. However, if you have an MRI with multiple lesions that suggest demyelination, your likelihood of eventually developing MS is about 80 percent.

That difference is quite substantial in terms of trying to plan treatment. So there is a great interest in identifying additional, easy-to-measure and reliable parameters that could predict who will end up with MS and who will not, or whether the individual is going to have an aggressive or mild course of MS.

Why is a blood test such an attractive concept?
If it turns out to be validated, a blood test is a very simple thing to do. It's minimally invasive and relatively inexpensive. Theoretically, the test could be given to people when they have their first isolated syndrome and help guide their doctors in terms of predicting the eventual development of MS. It could also help in terms of considering instituting therapies early on, or following patients more proactively, as opposed to just waiting until they come back with another episode.

What are the blood tests measuring?
The blood tests are measuring antibodies that are produced by the immune system and recognize myelin. Doctors have known for a long time that many MS patients have an unusual antibody response within the central nervous system. Myelin is one of the components thought to be a target of attack in the brain. In this study, the blood test measured antibodies that targeted two particular proteins within the myelin, one being myelin basic protein (MBP) and the other one being myelin oligodendrocyte glycoprotein (MOG). Those two proteins have been considered potential targets in MS for a long time.

This study showed that if you identify antibodies directed against these particular targets, you might have additional information in terms of predictive value. The research still doesn't tell doctors whether or not these antibodies are causing damage or whether they just represent a marker of immune system activity. It is also possible that someone could have these antibodies but not have MS, or neurological symptoms.

What questions still need to be addressed?
One would want to see these results validated in another study. The other thing of interest is how this antibody test relates to the predictive value of MRIs. Is the combination of MRI and the antibody test going to be helpful? Or will they be overlapping in terms of their predictive ability?

In the future doctors will start to apply a similar assay to their patient populations and follow them prospectively. And so there will be information coming out over the next couple of years.

Another initiative is prospectively following the pediatric population with MS. Doctors are adding this blood test to other measures, such as MRI and comprehensive immunological studies. The pediatric population offers a unique opportunity to understand the predictive value of tests done early on in the disease process.

How could the test affect treatment?
This kind of information can be helpful in allowing people to have discussions about MS therapies early on.

This is important because experts now recognize that people with MS have perhaps tenfold more underlying activity than what is apparent during attacks, and those attacks are likely to be associated with damage to the central nervous system. The reason that patients don't necessarily experience deficits early on is because there is reserve built into the nervous system, just as there is with any other organ of the body. So as you're waiting and considering therapy, more damage may be occurring, which is a reason for considering early intervention. And for that decision you want to have early and accurate diagnosis.

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