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Early MRI data predicted long-term outcomes 15 years after clinically isolated syndrome (CIS) -- symptoms that can, but do not always, develop into multiple sclerosis (MS) -- a longitudinal study showed.

Spinal cord and gadolinium-enhancing lesions had consistent links with secondary progression MS development and physical disability 15 years after the onset of the first symptoms of MS, reported Wallace Brownlee, MBChB, PhD, of University College London in England, and co-authors in .

Likewise, gadolinium-enhancing lesions were tied to cognitive performance 15 years later.

"The course of relapse-onset MS is difficult to predict in individual patients," Brownlee told 番茄社区. "Identifying patients at high risk of future disability and disease progression is important in making treatment decisions, particularly given the differences in efficacy and safety of currently available MS treatments."

The study tracked a group of patients who had CIS suggestive of MS, a "highly unique cohort of patients that's been followed in the U.K. for now more than 15 years," noted Robert Bermel, MD, of the Cleveland Clinic in Ohio, who was not involved with the research.

This research "addresses an issue we constantly have in MS, which is that we make short-term decisions and interpret data over a 6-month to 1-year to 2-year timeframe, hoping we make a difference in the long run," Bermel told 番茄社区.

"If I talk to patients with MS, their biggest fear isn't 'am I going to miss work next week because I have a relapse?' It's 'am I going to end up disabled 10 years from now?'"

"They're worried about long-term implications, and we do short-term management," he continued. "The way we do that is with MRI, largely, and this work validates a lot of what we had hoped to be true: that the short-term MRI measures we look at -- spinal cord lesions and gadolinium-enhancing lesions -- really do predict long-term outcomes."

In this study, Brownlee and co-authors followed patients who were prospectively recruited within 3 months of clinical disease onset from 1995 to 2004. Patients had brain and spinal cord MRIs at baseline (a median of 44 days after CIS onset) and after 1 year and 3 years. MRI assessments included supratentorial, infratentorial, spinal cord, and gadolinium-enhancing lesion number and brain and spinal cord volumetric measures.

After a mean of 15.1 years, 166 patients were assessed clinically to determine their disease course: 119 (72%) had MS, 45 (27%) remained as CIS, and two (1%) developed other disorders. Of patients with MS, 94 (57%) had relapsing-remitting and 25 (15%) had secondary progressive disease.

Overall, physical disability was low in MS patients (median Expanded Disability Status Scale score of 2, on a scale of 0 to 10) and 71% were untreated.

Baseline gadolinium-enhancing lesions (OR 3.16, P<0.01) and spinal cord lesions (OR 4.7, P<0.01) were independently linked with secondary progressive MS at 15 years. Of the 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant, and new spinal cord lesions over time were tied to secondary progressive MS.

Baseline gadolinium-enhancing lesions (β 1.32, P<0.01) and spinal cord lesions (β 1.53, P<0.01) also showed consistent links with Expanded Disability Status Scale scores at 15 years. Baseline gadolinium-enhancing lesions were tied to cognitive measures at 15 years, namely performance on the Paced Auditory Serial Addition Test (β -0.79, P<0.01) and Symbol Digit Modalities Test (β -0.70, P=0.02).

These findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset MS, Brownlee noted. "MRI metrics that are already available in clinical practice, like spinal cord imaging and contrast-enhanced MRI, may be helpful in counseling people with MS about their long-term prognosis."

The data also highlight the heterogeneity of MS, Bermel observed: "Everybody looks the same when they're sitting in front of you with CIS. Fifteen years later, one of those people is playing tennis; one of them is having some difficulty; and another one's in a nursing home."

"What we struggle with as neurologists is predicting who's going to be who as early as possible so we can make the right treatment choices," he said.

The study has several limitations, the researchers noted. Not all patients were able to return for an in-person follow-up visit after 15 years; 47 (29%) had their disease course and physical disability assessed by phone. Cognitive performance was assessed only once, at 15 years, in this study. Because the course of MS often unfolds over a time period longer than 15 years, the number of people developing secondary progression and worsening disability in this cohort is likely to increase with time, the team added.

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