Relapses and Progression of Disability in Multiple Sclerosis.

Relapses and Progression of Disability in Multiple Sclerosis Confavreux C, Vucusic S, Moreau T, Adeleine P (European Database for Multiple Sclerosis Coordinating Center and Service de Neurologic A, Hospital Neurologique and Unite de Biostatistique et Medical, Hospices Civils de Lyon, Lyon, France), N Engl J Med. 2000;343:1430-1438.

Multiple sclerosis causes irreversible disability in both the relapsing-remitting and primary progressive types of the disease. The relapsing-remitting onset type eventually leads to the secondary progressive form of the disease. This observational study on the natural course of multiple sclerosis describes the influence of acute relapses (ie, expression of acute inflammatory focal lesions) on the rate at which irreversible disability occurs and progresses. Progression of multiple sclerosis is manifested by demyelination, axonal loss, and gliosis.

The patient source was the Lyon Multiple Sclerosis Data Base (the referral center of multiple sclerosis in Lyon and the Rhone-Alps region since 1976). The database identified 1,562 patients with the relapsing onset form of the disease. In this form, the symptoms of neurologic dysfunction occurred, recurred, or worsened. The symptoms lasted 24 hours or longer and then stabilized or resolved partially or completely. The database identified 282 patients who had the primary progressive form of the disease from onset. These patients demonstrated a worsening of symptoms for at least 6 months with or without superimposed relapses.

At each clinic visit, each patient was assigned a disability score from 0 (no neurologic abnormality) to 10 (death from multiple sclerosis) on the Kurtzke Disability Scale in order to measure the severity and progression of the disease. Patients who walked without an aid or rest for more than 500 meters received a score of 4. A score of 6 was assigned to those patients requiring unilateral support to walk up to 100 meters. The most severe disability rating was 7, which was given to people who could walk for 10 meters only by leaning against a wall or holding on to furniture for support.

The median time interval from onset to developing irreversible disability was longer in cases of remitting-relapsing onset. The authors defined a patient's disability as irreversible if the patient had a disability score of 4 or greater for at least 6 months. The median times from onset to scores of 4, 6, and 7 on the Kurtzke Disability Status Scale were 11.4, 23.1, and 33.1 years, respectively, for patients with the relapsing-remitting form of the disease, and 0.0, 7.1, and 13.4 years respectively for patients with the primary progressive form. Once irreversible disability occurred, the progression of debility was not related to type of onset. The presence or absence of superimposed relapses did not affect the time course of the progressive phase in the primary progressive form of the disease, but they were related to a lengthened time course of increased disability in secondary progressive multiple sclerosis.

The authors concluded that, once a clinical threshold of disability is reached, relapses do not affect progression significantly. They believe that this result suggests that a biological dissociation exists between focal inflammation and progressive degeneration in the central nervous system. According to the authors, this paradox is consistent with observation of continued disease progression in patients treated with antileukocyte monoclonal antibody, and it suggests that drugs with a short-term effect on relapses may not delay the development of disability.

Judith A Verbanets, PT, MS
Del Mar, Calif