Study Examines Factors That Increase Risk of Progressing from RRMS to SPMS

Age at disease onset, number of early relapses, and the extent of brain damage at baseline can help identify those who are at high risk of progression from relapsing-remitting multiple sclerosis into the secondary progressive phase of the disease, a new study shows.

The study with that finding, “The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis,” was published in the journal Neurology.

Relapsing-remitting multiple sclerosis (RRMS) sometimes can evolve into a secondary progressive (SPMS) phase, which is much harder to treat. Unfortunately, the progression from RRMS to SPMS is largely unpredictable as little is known about the mechanisms that lead to the development of SPMS.

A lack of predictive biomarkers also makes it more difficult to identify patients at risk of developing SPMS, who consequently would require much more aggressive therapies.

The brain is divided into two types of tissue — white matter and gray matter. Injury to the gray matter of the brain plays a major role in the accumulation of long-term disability in patients with MS. In particular, studies have suggested that cortical lesions and cortical atrophy — representing damage to a part of the brain known as the cerebral cortex — can account for the transition to SPMS.

In an effort to learn more about the progression to SPMS, researchers set out to investigate the relationship between cortical changes, the number of early relapses, and the long-term course of MS.

Researchers assessed a number of parameters, such as the number of cortical lesions, white matter lesions, and cortical thickness at both onset of MS and at follow-up (mean of 7.9 years) in a group of 219 patients with RRMS.

After a mean of 6.1 years, researchers determined that 59 patients, or 27 percent, developed SPMS.

Patients who had a larger number of cortical lesions at onset had a higher risk of developing SPMS. Specifically, patients with two cortical lesions had a 2.16-fold greater risk of developing SPMS, patients with five cortical lesions had a 4.79-fold greater risk of developing SPMS, and patients with seven cortical lesions or more had a 12.3-fold higher risk of developing SPMS.

Patients with more cortical lesions also tended to have a shorter time to SPMS progression.

Patients were grouped by early relapse (ER) numbers during the first two years, including the low-ER group (one ER), mid-ER group (two ERs), and the high-ER group (three or more ERs).

Patients in the high-ER group compared to the low-ER and mid-ER groups had a larger volume of cortical lesions at onset and developed more cortical lesions. They also had larger volume of white matter lesions, experienced more severe cortical atrophy over time, and progressed to the SPMS more quickly.

Statistical analysis showed that an older age at onset, greater baseline cortical lesion numbers, larger white matter lesion volume, early changes in global cortical thickness, and three or more early relapses independently predicted a higher probability of developing SPMS.

Researchers hypothesize that this is likely due to the fact that extensive cortical damage at disease onset is associated with high levels of inflammatory activity and predisposes patients to more quickly develop SPMS.

Based on the results, the team concluded: “Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.”