Younger Age, Earlier Disease Onset Predict Benign MS Course

Daniel M. Keller, PhD

November 08, 2019

DUBAI, UAE — Benign multiple sclerosis (BMS) remains a controversial condition; whether it exists at all, and if it does, how to predict which patients will have a benign course is an open question.

A new 5-year study of multiple sclerosis (MS) patients meeting enrollment criteria found that prognostic factors for a benign course included younger patient age, earlier disease onset, monosymptom at onset, female gender, and being at the lower end of the Kurtzke Expanded Disability Status Scale (EDSS) after 10 years of disease.

Olga Shulga, MD, PhD, of the Volyn Regional Clinical Hospital in Lutsk, Ukraine, said 85% of patients stop working within 15 years of onset of the disease because of disability, but others have a more benign course, and they formed her study cohort.

This prospective study enrolled patients from January 2012 to January 2013 with EDSS ≤ 4, disease duration ≥ 10 years, and who were fully or partially employed. They were then followed for 5 years.

The aim was to define predictive factors and to design a prognostic model for a benign disease course. She presented her findings here at the XXIV World Congress of Neurology.

From a regional registry of all MS patients, 80 (12.6%) were enrolled in the study, of whom 74 (48 females, 26 males) completed it in 2017-2018.

The mean age was 46.45 ± 8.36 years with an age at disease onset of 30.71 ± 9.1 years. Forty-four had monosymptomatic onset compared with 30 who had multifocal symptoms. After 15 years of disease, 44 of the 74 (59.5%) had had a benign course.

Compared to baseline at study entry, at the 5-year endpoint of the study the cohort showed significantly more impairment on six of the eight functional system components of the EDSS as well as on the total EDSS score: 3.05 ± 0.85 at entry vs 3.54 ± 1.31 at year 5 (P < .001).

Based on EDSS score distributions over the 5 years, men fared worse than women (P < .035). The investigators estimated that after 5 years of follow-up, 34 of the 74 (46%) patients continued to have BMS.

Using registry data, the investigators developed two mathematical models to predict a benign disease course. One used type of onset and age of first symptoms. It accurately predicted 74% of cases of BMS after 15 years, 63% of cases with a nonbenign course, and 68% of correct classifications for the data set as a whole.

The second model, based on differences in the eight functional systems comprising the total EDSS, appropriately classified 76.47% of cases of BMS after 15 years, 85% of cases that were nonbenign, and 81.08% for the data set overall.

Limitations of the study included that participants' level of education was not taken into account, nor was the dependence of the employment on functional capabilities. Importantly, the investigators did not evaluate the role of immunomodulatory therapy.

After the presentation, session co-chairs Nikolaos Grigoriadis, MD, PhD, of Aristotle University in Thessaloniki, Greece, and president of the Hellenic Neurological Society, and Raed Alroughani, MD, head of the MS Clinic at Dasman Research Institute and a consultant neurologist at Al-Amiri Hospital in Kuwait City, offered Medscape Medical News their perspectives on just what may constitute benign MS and the intricacies of trying to define it.

Alroughani said BMS is a debatable issue, with some MS experts believing it can exist.

"Others say no, it's a progressive disease and no one should label a patient as benign," he said and pointed out that BMS is a retrospective diagnosis, without consensus on a definition. "Some people say you need at least 10 years, others say 15, some others say you need 20 years before you call them a benign MS."

He noted that studies and experts have used different EDSS cutoffs of 2 or 3 to define BMS, and others do not believe in it at all. "If you perform more tests and you detect more disability, especially cognitive impairment or a hand impairment, functions that cannot be tested with EDSS, you will see disability, and you cannot call it benign MS," Alroughani explained.

Grigoriadis said treatment becomes a dilemma if there is such an entity as BMS. "Now, those who were not on treatment and go for 15, 20 years with EDSS 2 or less off treatment, maybe these are the true benign," he said. "To withdraw a treatment from any patient who was stable, either benign or nonbenign MS, it's a tricky one."

He cited a few studies indicating that a third of these patients will relapse, a third will progress, and a third will have stable disease. "So you have to inform the patient that . . . when you stop DMTs [disease-modifying therapies], there is a chance of relapse or a progression over time, and a patient has to be aware of this," he cautioned.

He asked if someone responds well to a DMT long-term does it mean that he is a good responder to the drug, or might he have BMS? "I think that we will not be able in the [next] few years to come even to study it because most of the patients that need a DMT would have access and have a DMT, so we really cannot identify this group of patients," he said.

An opportunity to approach the question may exist in some countries where not all patients have access to DMTs, but it still gets back to a definition of BMS. Grigoriadis gave as an example a person with EDSS 1.

"He can run, he can do everything, but he has cognitive deteriorated deficit. Is this a benign MS?" he asked. "We need to redefine what do we really mean when we say 'disability.'"

Shulga, Grigoriadis, and Alroughani have disclosed no relevant financial relationships.

XXIV World Congress of Neurology 2019. Presented October 28, 2019.

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