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Muliple Sclerosis: An Autoimmune Disorder

By Dr. Shafiq Qaadri, MD

What is Multiple Sclerosis?
Multiple sclerosis is a disease affecting the central nervous system, mostly in young adults. It is characterized by damage to myelin, the insulation that surrounds the axon of a nerve. This decreases nerve conduction and causes neurological symptoms.

Is MS an autoimmune disease?
That’s a theory…an autoimmune phenomenon is going on. Myelin is being attacked by immune-active cells.

We’re not sure if the abnormality in the immune system is a cause or whether it’s the result of the disease.

Is climate to blame—for example, those living in a colder climate may be more predisposed to developing MS.
There is no question that there is a geographical distribution of the disease. It is very uncommon at the equator, and the farther you go away from the equator, the prevalence of the disease increases. In zones like Canada, the Northern United States, or Great Britain, or Central Europe, the incidence of the disease is much, much higher.

That may be related to geography, but it’s also possible it may be due to genetic drift: people with the predisposition migrated to these areas. Or it may be related to certain infections that occur in certain areas of the world.

Is the course of MS always slow and progressive, and why is that?
The course is extremely variable. You can have patients who have a rapidly progressive disease over a number of years. But you can have other patients who look and feel reasonably well for 20 to 25 years.
Most patients, however, are in between. Over the course of decades, they do show increasing disability.

Does the primary attack of MS always follow a fever?
No, but it is a common occurrence. Most episodes seem to appear rather spontaneously. Most infections don’t cause attacks, but there is a relationship.

Also, the postpartum period: After delivery, there are more attacks of MS.

For a family physician, what might be the typical symptoms of an MS patient.
There are several common symptoms that don’t go away: numbness that lasts longer than two weeks, double vision, or loss of vision in an eye.

One of the difficulties is that MS symptoms are rather non-specific; for example, a patient may notice increasing fatigue, or their legs are not as strong or steady as they should be.

In the early stages, it’s easy to dismiss some of these symptoms.

What is the mechanism for the motor symptoms—for example, shaking, loss of coordination, unsteadiness?
The MS motor symptoms are important because they are accompanied by problems in function.
If one has a problem with weakness or steadiness, then it can affect your walking, mobility, and use of your hands. Those symptoms are less easy to dismiss than things like numbness or tingling.

The motor problems can occur from a number of different areas in the nervous system. There’s a pyramidal system, which is responsible for motor movement. There’s also the cerebellar system--that’s responsible for coordination of movements. So if you have the pyramidal system affected, you’ll often develop weakness and spasticity, which are common problems in MS.

When the cerebellar system is involved, you get incoordination or tremor when a person tries to carry out an action, such as writing with a pen or using a knife and fork.

Are MS patients hypersensitive to pain, or is it the opposite?
They are not hypersensitive to pain, but MS is often associated with problems that produce pain. For example, their spasticity may produce aching pain and cramps in muscles. They can also experience nerve pain. The best known is trigeminal neuralgia—a knife-like, lancinating pain that occurs recurrently in the face.

Studies done by our Halifax group show that 54% of MS patients complain of pain at some time.

Are the mood symptoms—for example, depression—a consequence of the disability, or is there a direct brain effect?
For a century, people have wondered whether the mood changes that occur were related to the disease or related to the stress of having the disease.

It’s probably both. It’s clear that to deal with a frustrating, chronic disease that affects your function, would lead to depressive episodes.

But we also know that the disease itself is capable of producing emotional and cognitive changes. That may affect their mood and emotional state and also can affect their sense of concentration and their speed of new learning.

There are some very unusual but peculiar emotional states that can occur in MS, characterized by pathological laughing or pathological crying. These are very distressing to the patient, because they will laugh when they don’t find anything amusing or funny, or weep when they don’t feel sad.

Are bowel, bladder and sexual problems very common—and what is the mechanism there?
The nerves that control the bladder overlap the same part of the nervous system that controls the legs. So when people develop spasticity, they have associated bladder spasticity.

This is quite distressing as it limits their social function. This can, however, be controlled by relatively simple medications and advice. But bladder frequency, urgency and incontinence are not uncommon.

Bowel control problems are less common. Impotence is a problem that is distressing to many of the males with MS, but there are new therapies.

What is the prevalence of MS in North America, and can family physicians expect to see MS patients in their practices?
The average family practitioner may have three cases of MS in their practice, based on the figure of one case in 500 people. But it’s becoming clear from studies that the figure is undoubtedly much higher than that, perhaps even one in 300.

If a family physician suspects MS in a patient, and refers him to a neurologist, what is the usual diagnostic procedure?
The most important step when a patient is suspected of having MS is to have a careful history and physical examination. Despite the fact that MS is said to be a difficult diagnosis to make, in most instances, the history and physical examination makes it clear.

To be definitive, MRI has been the most important diagnostic advance. There are also spinal fluid tests that can be done, as well as nerve conduction-rate studies. The most important of these is the visual evoked potential rate study, to look at the rate of conduction of the optic nerve.

Why does the course of MS seem to have exacerbations and remissions, and how is it someone can be in a wheelchair one year, and walking the next year?
Two peculiarities were noted 125 years ago. One, it was a neurological disease that affects young adults, characterized by relapses and remissions. Most nervous system diseases seem to be progressive, but this one could have dramatic remissions.

It’s not uncommon to hear of patients who had attacks that were quite severe, to the point they were wheelchair-bound, then recover from that, almost to normality.

It does create some difficulty, because no matter what treatment the person took, it would seem to be responsible for the remarkable recovery. And that’s why you hear about all sorts of unusual therapies. We may be observing the natural history of the disease.

What is Interferon, and why has it been talked about as an agent for everything, from MS to cancers?
Interferons are naturally occurring substances in the body, and they modulate the immune system.
The development of the Interferons over the last 25 years has led to the concept that if we could modulate how the immune system responds, in particular how it responds to itself, that we could have a better effect.

Later, it was quite clear that we could affect the outcome of MS by treatment with Interferons.

There are different Interferon drugs on the market—for example, Betaseron, Avonex, and Rebif. All have been shown to have an effect in reducing the number of attacks of MS, and the severity of the attacks.

They have a remarkable effect on cutting down the number of new lesions found on the MRI, and there’s increasing evidence to suggest that the longterm progression of the disease is being modified.

They do not stop the disease or reverse the disease, but they do improve the long term outcome. There’s another immune-modulating drug that’s not an Interferon, called Copaxone.

What is importance of early treatment, especially in light of two studies that are gaining attention, CHAMPS and ETOMS?
The CHAMPS Study was designed to see if patients who were at risk for developing MS would benefit from being treated when they developed their first symptoms. The ETOMS Study has the same concept: Treat people very early.

The CHAMPS Study looked for patients who had just had their first symptoms that looked like MS, and then had an MRI that were characteristic of MS. These patients were called at-risk for MS.

These patients were treated in the first two weeks of their first symptoms in the CHAMPS Study, and their chance of developing their second attack, confirming MS, was 44% less than those treated with placebo.

It also seemed that patients who were treated early continued to have a benefit over those who were not treated, or who were treated later.

How do you take Interferon?
These agents are all injectables. Avonex is given by intramuscular injection, whereas the others are subcutaneous. Betaseron is given every second day, Rebif is given subcutaneously three times a week, and Avonex is given once a week.

Is there hope for patients with MS?
Yes, there is a sense of progress in the research that’s going on. We are learning more about the underlying mechanisms of the disease. We know we’re developing therapies and combining drugs that for the first time are having a significant impact.

Dr. Shafiq Qaadri is a Toronto family physician and Continuing Medical Education lecturer. www.doctorQ.ca

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