Multiple Sclerosis: Making a Diagnosis

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The MD Magazine Peer Exchange “Strategies in the Management of Relapsing-Remitting Multiple Sclerosis” features a panel of physician experts discussing the importance of early therapy in multiple sclerosis treatment, factors that affect choice of management strategy, the need for ongoing monitoring, and other aspects of treating patients with multiple sclerosis.

This Peer Exchange is moderated by Fred D. Lublin, MD, FAAN, FANA, Saunders Family Professor of Neurology and director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Icahn School of Medicine at Mount Sinai, New York.

The panelists are:

• Patricia K. Coyle, MD, professor and vice chair (Clinical Affairs) and director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University Medical Center, New York
• Clyde E. Markowitz, MD, associate professor of neurology and director of the Multiple Sclerosis Comprehensive Care Center at Perelman School of Medicine, University of Pennsylvania, Philadelphia,
• Claire S. Riley, MD, assistant professor of neurology and director of the Columbia University Multiple Sclerosis Clinical Care and Research Center, Department of Neurology, Columbia University, New York

Dr. Coyle says she thinks that clinicians do not do enough spinal fluid analysis when diagnosing patients for potential multiple sclerosis (MS). “I really think, to make an early diagnosis, spinal fluid adds an invaluable addition to the neuro imaging,” she says.

Dr. Markowitz notes that there are many cases when a patient’s MRI clearly indicates MS, in which case he doesn’t think a spinal tap is necessary.

According to Coyle, “There is no absolute diagnostic MRI scan. No one is good enough to look at an MRI scan in isolation… We have no diagnostic biomarker at this point. So, I think a multimodality approach makes you most confident.”

Dr. Lublin points out that one reason why CSF (cerebrospinal fluid) is only in the guidelines for primary progressive MS is that is the form of MS that’s most likely to be misdiagnosed, so having the additional data from the spinal fluid is helpful.

“CSF wasn’t included for the relapsing forms of MS because there were no data. When the MRI investigator groups looked at the different metrics—more than one lesion in 2 elephant areas, MS specific areas, and enhancing and non-enhancing lesions—they didn’t have CSF data to further characterize,” he notes.

When diagnosing a patient, Dr. Riley asks whether clinicians look for positive evidence from the CSF of another disease state, or do they look for the presence of oligoclonal bands?

Coyle says she is much more comfortable making a diagnosis of MS when there are positive oligoclonal bands in spinal fluid.

Lublin agrees that, in cases where diagnostic uncertainty exists, “having the spinal fluid is very useful, and radiologically isolated syndrome, by definition, is diagnostic uncertainty…and the spinal fluid is actually very helpful because it increases the odds of going on to actually developing MS several fold—by quite a bit in radiologically isolated syndrome. It’s a matter of how much uncertainty you have when you’re diagnosing.”

Coyle proposes that clinicians should start using “active” and “non-active” over a defined timeframe and “progressing” or “not progressing,” because “that’s going to help us enter better patients into trials, but also begin to think about the patients better.”

Lublin agrees, noting that “in a defined timeframe” is the key. “Activity, as we define it is either a relapse, or a gadolinium enhancing lesion, or a new or unequivocally enlarging T2 lesion. But it has to be framed in time,” he says.

“For relapsing patients, we recommend a minimum of one year, which means they ought to have at least an evaluation once a year both clinically and an MRI. Frankly, if they’re on therapy, I think much more frequently. But that gives you a frame. When we see someone in clinic we’ll just say, ‘relapsing-remitting’ or ‘active.’ I usually write down, ‘by MRI’ or ‘by clinical past year,’ or even the ‘past six months.’ And the same thing with progressing or non-progressing,” Lublin says.