The findings of a multicenter, multinational cohort study of radiologically isolated syndrome (RIS) published online ahead of print November 24 in Annals of Neurology offer further evidence that the condition should be considered part of the multiple sclerosis (MS) treatment spectrum because of the rate at which patients progressed to primary progressive MS over the course of the study.
“This is the first report of the temporal course within the preprogression phase for an extremely rare group of subjects originally identified by MRI as having asymptomatic disease, who ultimately experienced progressive symptom evolution consistent with primary progressive MS that could not otherwise be explained by any other mechanism (excessive alcohol use, vitamin deficiencies, etc.),” said Orhun H. Kantarci, MD, Assistant Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.
Dr. Kantarci and his coinvestigators evaluated 453 patients with RIS at 22 centers in the United States, France, Italy, Spain, and Turkey. The researchers also collected data on MRI, lesions, and CSF at baseline and during follow-up for as long as 20 years in certain cohorts. Demographic and clinical data were also analyzed for each patient enrolled.
Ultimately, 128 (28%) of the 453 patients with RIS developed symptomatic MS. Of these patients, 15 (12%) evolved to primary progressive MS and the remaining 113 patients “developed a first acute clinical event related to CNS demyelination consistent with clinically isolated syndrome [CIS]/MS diagnosis.” RIS occurred at a median age of 43.3, with an age range of 20 to 66, and evolved to primary progressive MS at a mean age of 49.1. The median time to conversion was 3.5 years over a median follow-up period of 5.8 years.
Nine patients with primary progressive MS were male, and the remaining six were female. Patients with primary progressive MS were more likely to be men, compared with patients who developed CIS/MS. In addition, median age at the onset of RIS and median age at symptomatic evolution were both older by about 10 years in patients with primary progressive MS versus patients who developed CIS/MS.“The 12% prevalence of primary progressive MS in this large RIS cohort, as well as age at primary progressive MS onset, is strikingly similar to that of large clinical studies in MS,” the authors noted. “Studying RIS, therefore, provides an opportunity to better understand the onset of clinical MS and to test early intervention.”Dr. Kantarci and his associates also pointed out that, in their study, the older age of primary progressive MS onset versus CIS/MS was “clearly” independent of individual follow-up times. Therefore, they also concluded that “age dependence of progressive MS development, in the absence of previous clinical relapses despite having clear subclinically active MS, suggests that biological aging mechanisms may be a significant contributor for development of progressive MS.”
—Deepak Chitnis