In Multiple Sclerosis, Do Relapses Make Disability Worse?

From the WebMD Archives

Nov. 15, 2000 -- A controversial new study has found that patients with primary progressive multiple sclerosis become disabled faster than those with relapsing-remitting multiple sclerosis, which goes against the medical community's most widely accepted theory. However, the controversy comes from the finding that once both groups reach a certain level of disability, subsequent relapses don't alter the time it takes to reach progressively worse disability.

Early in the course of multiple sclerosis, most patients have attacks of neurologic symptoms that disappear as rapidly as they appear. Between relapses -- marked by vision loss, numbness, or weakness -- patients may appear and feel perfectly normal. But as this relapsing-remitting form of the disease progresses, recovery from these attacks is incomplete, eventually leaving the patient with complete disability.

About 15% of multiple sclerosis patients have a form of the disease called primary progressive, without clear-cut remissions during which symptoms improve, but with continuous deterioration to total disability.

"Relapses do not significantly influence the progression of irreversible disability" write the authors of the new study, published in the Nov. 16, 2000 issue of TheNew England Journal of Medicine.

"No practicing neurologist on the planet believes that," John Corboy, MD, who was not involved in the study, tells WebMD. "It's a question of what you look at to define disability, and how and when you look at relapses," says Corboy, an associate professor of neurology and director of the multiple sclerosis clinic at the University of Colorado Health Sciences Center in Denver.

"I don't think their conclusion is justified," Douglas R. Jeffery, MD, PhD, tells WebMD. Although progression of disability was clearly worse in patients whose disease was progressive from onset, that does not mean that progression was unrelated to relapses, says Jeffery, who also wasn't involved in the study.

According to Jeffery and Corboy, recent studies show that most patients do not make a complete recovery following relapses, and that disability gets progressively worse with each relapse. This is what doctors usually see in their practices, Jeffery says.

The new study looked at nearly 2,000 patients in a database for multiple sclerosis in Lyons, France. Researchers determined when each patient's symptoms began and relapses occurred, and measured progression of disability.

Because the researchers depended on the patients to report accurately on the progression of their disease, they looked at levels of disability that would be easy for the patients to remember -- their ability to walk. The patients rated themselves according to the distance they were able to walk, with a higher score meaning more disability.

It took longer for patients who started out with the relapsing-remitting form of the disease to reach higher scores than it did patients who had progressive disease from the outset. Yet once patients reached a certain level of disability, it took them the same amount of time to progress to a further level of disability -- regardless of which group they were in.

"Once a clinical threshold of irreversible disability has been reached, the further progression of disability is not affected by relapses," lead author Christian Confavreux, MD, professor of neurology at Hôpital Neurologique in Lyons, tells WebMD.

"Progressive [multiple sclerosis] is a different creature altogether from relapsing-remitting [multiple sclerosis], biologically as well as clinically," says Corboy. In relapses, the immune system attacks nerve coatings called myelin, disrupting communication between nerves, which causes the symptoms. When the attack subsides, either on its own or as a result of drug treatment, the symptoms go away.

But in progressive multiple sclerosis, nerves are irreversibly injured, causing shrinking in the brain or spinal cord visible on MRI scans. Studies have shown that treating relapses with drugs early in the course helped prevent or delay disability, Corboy explains.

"A comprehensive therapeutic strategy ... must be directed against inflammation but also against degeneration of the central nervous system," says Confavreux. Drugs that prevent relapses may not necessarily delay long-term disability.

"Relapse prevention management continues to be an important aspect of [multiple sclerosis] care and treatment," argues Jeffery.

"Now we're getting a feel for how disability occurs," Randall T. Schapiro, chief of neurology and director of the multiple sclerosis Center at the Fairview University Medical Center in Minneapolis, Minn., tells WebMD. "That should help us determine the relevance of our treatments."

One expert not involved in the study drives home the bottom line. "Relapses are disturbing to patients, but the gold standard for treatment should be prevention or slowing of physical disability," Lawrence Jacobs MD, tells WebMD. "Patients and their families are most concerned with how physical disability will change with time, with when they will need a cane or a wheelchair," says Jacobs, professor of neurology at SUNY at Buffalo.