Multiple Sclerosis : Diagnosis, Treatment

by Food and Drug Administration (FDA)

(Page 2 of 3)

Difficult Diagnosis

To formally diagnose MS, there must be disease "disseminated in time and space," McFarland says. That is, there must be at least two attacks that affect different areas of the nervous system. This is needed to rule out other problems, such as a stroke or tumor, that could cause the same symptoms as MS. When the symptoms come and go and affect different functions, a diagnosis of MS is strengthened.

The first symptom that sent Krebs to see her doctor in 1984 was optic neuritis, which caused partial loss of her vision. In retrospect, she remembers earlier instances of lethargy and problems with balance, causing her to bump into objects. She had a second episode of optic neuritis in late 1985. When, in 1987, she developed numbness and weakness in her leg, MS was diagnosed.

Even in disease separated in time and space, MS is only diagnosed if there is no other reasonable cause for the symptoms, such as a malignancy, another neurological disorder, or an autoimmune disease like lupus erythematosus.

Laboratory tests, although not diagnostic in themselves, can help confirm suspected disease and identify additional lesions.

Magnetic resonance imaging (MRI) scans are very reliable in detecting MS lesions. Although not everyone who shows central nervous system lesions on MRI has MS, the test detects MS lesions in more than 90 percent of patients who have clinically diagnosed disease. This makes it a valuable tool for confirming disease and tracking its progress. In fact, McFarland says, only a small portion of MS detectable on MRI manifests clinically.

"Many patients who have extensive disease activity on MRI don't have a high rate of relapse," he says. "Someone with a relatively mild form of MS may not experience symptoms for a long time. That may be, for example, what's happening in the rare individuals who are not diagnosed until age 60."

Evoked response tests assess the integrity of the nervous system. In a visual evoked response test, for example, electrodes are placed on the patient's head and a visual pattern, such as a checkerboard, is flashed on and off. The time it takes for the message, or pattern, to reach the occipital cortex of the brain, where visual messages are recognized, is measured in both eyes. Frequently in MS, there is a delay in conducting that impulse. Similar tests are used to evoke other sensory responses, on the arms or legs, for example.

The physician may also do a spinal fluid examination, drawing a small amount of fluid from the spinal cord to measure levels of certain antibodies that are elevated and have a distinct pattern in many patients with MS.

Treatment

While a cure for MS still eludes science, treatment focuses on preventing flare-ups or prolonging the time between them, shortening the duration of attacks, and relieving symptoms.

Betaseron, licensed to treat patients with the relapsing remitting form of MS, is the only product on the market that can help stave off relapses. Others treat the flare-ups and symptoms.

When Krebs was given her first dose of Betaseron in October 1988, she didn't know at the time just what she was getting. As a study participant, she didn't know if she was in the group of patients receiving high-dose Betaseron, low-dose Betaseron, or a placebo — an inactive substance.

Five years later she learned she was on the high-dose regimen — the one shown to be effective — and she credits Betaseron with the lengthy remission she's enjoyed since her last flare-up.

"I haven't had an attack since February 1990, and that one was mild," Krebs says. "I didn't lose vision or have any numbness. My left foot was dragging and that lasted a couple months, but it was a shorter time than before I went on Betaseron."

"Betaseron is a synthetic version of interferon beta — a naturally occurring protein the body uses to regulate the immune response," says Janet Woodcock, M.D., director of FDA's Office of Therapeutics Research and Review in the Center for Biologics Evaluation and Research. "We don't know what property makes it effective in multiple sclerosis, but it does help prevent flare- ups."

Woodcock notes that the agency's top priority review of Betaseron under accelerated approval regulations is an example of getting an important product onto the market as fast as possible with the most reasonable amount of information needed to decide if it's safe and effective.

"In this case, we found that Betaseron was safe and effective based on a two-year clinical trial of 372 patients," she says. "Patients on Betaseron had fewer flare-ups and more patients were completely free of flare-ups over the study period."

The main side effects of the biologic, which the patient injects every other day, are inflammation and pain at the injection site and flu-like symptoms. Occasional serious side effects include abnormal liver function tests and severe depression.

Licensing was based not only on Betaseron's effectiveness in reducing relapses, but on supporting data from magnetic resonance imaging (MRI) brain scans. The scans showed that at the end of the study, patients taking Betaseron had a smaller volume of brain lesions than those given placebo.

About the Author

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