Multiple Sclerosis Treatment Reduces Relapses

by Food and Drug Administration (FDA)

Martha Krebs is tired today, having spent a long day at the University of Maryland's medical school in Baltimore undergoing her last test as part of a study for a new treatment for multiple sclerosis.

The 35-year-old Germantown, Md., woman was diagnosed with multiple sclerosis — a disease caused by inflammation and scarring of brain and spinal cord tissue — in August 1987, two weeks before her wedding day.

The treatment Krebs received in the study was Betaseron (interferon beta-1b), a biologic product. In July 1993, after studies showed it to be safe and effective, FDA licensed Betaseron, making it the first product developed specifically for multiple sclerosis (MS) to come on the market. Because of the importance of Betaseron, FDA gave its review top priority, and it also became the first biologic to be licensed under the agency's accelerated approval regulations.

Krebs is one of an estimated 300,000 Americans with MS. The disease primarily strikes young adults between 20 and 40 years old, but, rarely, can develop in children or in older adults in their 40s or even 50s. It affects about twice as many women as men.

MS is a problem of communication within the nervous system. Nerve cells send messages from the brain in the form of electrical impulses that travel along nerve fibers (axons) branching out from the cell body (neuron). These messages direct vital processes that, among others, enable us to breathe, eat, see, feel, walk, and talk. When the impulse is delayed or blocked, physical symptoms can result. Impaired optic nerve function, for instance, can cause blurred vision or blind spots.

The electrical impulses are hastened on their way by myelin- -a white, fatty substance coating the nerve fiber.

"There are little gaps in the myelin called nodes of Ranvier," explains Henry McFarland, M.D. "The impulses jump from one gap to the next, a bit like a rock skipping across a pond. The myelin acts like a capacitor."

McFarland, a neurologist at the National Institute of Neurological Disorders and Stroke, explains that in MS, inflammation destroys patches of myelin in brain and spinal cord nerve fibers, leaving scar tissue. When the impulse reaches a point stripped of myelin, its progress down the bare axon is slowed. The more demyelination, the slower the conduction.

Scientists don't know what causes MS, but suspect it's an autoimmune disease, in which the body mistakenly reacts against its own tissues, attacking the myelin (see accompanying article). The resulting inflammation and edema (fluid buildup) further impede conduction. Once they subside, symptoms often improve.

Blurred or double vision is often the first symptom of MS. Other early symptoms are tingling, numbness, or weakness of a leg or hand, clumsiness, fatigue, dizziness, and loss of balance.

In many patients, symptoms get worse when their body heats up from exercise or being out in the sun. "People get upset, thinking it means the disease is getting worse," McFarland says. "It's not." He explains that sodium channels along the axon are involved in creating the nerve impulse, while potassium channels act the opposite. Demyelination exposes the potassium channels, and when the body heats up, they become more active and can completely block the impulse. When the core temperature goes back down, the impulses normalize.

Unpredictable Course

MS most often begins as a "relapsing remitting" disease — flare-ups of symptoms followed by recovery.

"One day you may wake up with blurred vision or be unsteady on your feet," McFarland explains. "That may worsen a little the next few days and then level off for a couple days or weeks. Then, it will usually get better spontaneously, without treatment. You may then have no problem for the next six months to a year or year and a half and then have another attack somewhere else in the nervous system, with the same course."

Scientists don't know what triggers relapses; most have no evident precipitating event. There is, however, some increased risk following a viral infection. There is also greater likelihood of a relapse in the six months after pregnancy, although during pregnancy the risk is decreased. Some have argued that stress, injury and trauma can trigger attacks, but these claims have not been supported scientifically.

Over time, recovery after each relapse may no longer be complete, and the patient is left with some permanent disability. After some years, additional episodes cause further physical decline in a "relapsing progressive" pattern. Often, these patients go on to develop "chronic progressive" MS, characterized by steady deterioration.

How the disease will progress in a given individual is impossible to predict with certainty. Even so, McFarland says, the pattern of attacks over the first five years may indicate the long-term course. Some patients have very benign disease and never experience anything more than mild disability, while others develop more severe problems, such as loss of bowel or bladder control, sexual dysfunction, paralysis, and confinement to a wheelchair. Krebs' doctors suspect her disease, which has progressed little in the 10 years since her first attack, will remain mild.

In some patients, MS is chronic progressive from the start and, rarely, it can take a rapid, severely debilitating course that ends in early death. Most patients, however, can expect to live a normal lifespan, and many of those with mild relapsing symptoms may never even know they have MS.

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