Defining Transitional MS Remains a Tricky, but Important, Problem

July 2, 2020

Most patients who have multiple sclerosis (MS) begin with a relapsing-remitting phase and eventually transition to a secondary progressive phase. In between is believed to be a “transitional” phase, but scientists have yet to discover how to clearly identify patients in transition.

Most patients diagnosed with the relapsing-remitting form of multiple sclerosis (MS) eventually transition to secondary progressive MS (SPMS), which is characterized by a progressive worsening of the condition.

However, while doctors are able to distinguish between patients in the two stages, it is not yet easy to identify patients who are in the process of transitioning from one stage to the next. In a new review article, investigators from Germany and Russia outlined the latest research attempting to help define “transitional MS.” Their report was published in the journal Multiple Sclerosis and Related Disorders.1

“Clinically, ‘transitional MS’ is a prequel of SPMS with signs of incipient progression during a variable duration of time before SPMS is unequivocally diagnosed,” wrote corresponding author Ingo Kleiter, MD, of the Mariane Strauss Clinic, in Germany, and colleagues.

A 2015 study2 suggested that the mean duration of “diagnostic uncertainty” between the two phases was 2.9 years, they said, “and in 70% of the cases, the diagnosis of SPMS was only established when an [expanded disability status score] of ≥6.0 was reached.”

One symptom of MS progression is cognitive decline and fatigue, but the investigators said those can be difficult metrics to conclusively track, in part because some patients can handle the disease burden better than others. However, the investigators said the most marked difference between patients in RRMS versus those in SPMS was in visuospatial short-term memory and learning, which therefore might be the best cognitive method of tracking transition.

MRI is another way to note MS progression, though there are currently no established parameters to measure progression. Still, the authors pointed to a few imaging findings they said are typically associated with the transition phase.

“Higher numbers of new and enlarging cortical lesions, incipient gray matter and cortical atrophy as well as atrophied lesions may provide indicators of transitional MS,” they said.

Biomarkers are also currently being investigated, which may offer keener insight into when patients are undergoing transition. Similarly, retinal optic coherence tomography might someday hold promise as a diagnostic tool, though at present the screenings have only been shown to be predictive at a population level, and not at an individual level.

One question raised by the study of this transitional phase is whether the wave of disease-modifying therapies will open up the possibility of preventing the transition to SPMS. Prevention, and not simply delay, would be optimal, the authors said.

“So far, therapeutic trials in patients with established SPMS have shown disappointing or at best modest benefits,” they reported. “Therefore, preventing or delaying the conversion to SPMS during the transitional phase appears a worthwhile approach.”

Right now, the authors said, there is a dearth of studies that look specifically at how DMTs affect the transitional phase of the disease. In order to fix that problem, the authors said, scientists would need better criteria to identify patients at or near the transitional phase. That, too, will require additional research.

“A prospective observational clinical study should aim at gathering data that allow a more thorough characterization of transitional MS and estimate treatment effects of potentially promising therapies,” they said.

For now, the goal should be excluding people with early MS or clear RRMS, as well as people firmly into the progressive phase of the disease.

References

  1. Kleiter I, Ayzenberg I, Havla J, et al. The transitional phase of multiple sclerosis: Characterization and conceptual framework [published online ahead of print, 2020 May 29]. Mult Scler Relat Disord. 2020;44:102242. doi:10.1016/j.msard.2020.102242
  2. Katz Sand I. Classification, diagnosis, and differential diagnosis of multiple sclerosis. Curr Opin Neurol. 2015;28(3):193-205. doi:10.1097/WCO.0000000000000206