Robert J. Fox, MD: The main concept behind the diagnostic criteria for multiple sclerosis [MS] is repeated episodes of demyelination disseminated both in space—different places in the central nervous system— and in time, multiple time points. Originally that was defined simply by clinical criteria—multiple episodes affecting different parts of the central nervous system at different points in time.
With the development of MRI [magnetic resonance imaging] in the 1990s, we were able to better understand the disease and develop better diagnostic criteria for the disease that included MRI. The original McDonald criteria were the first criteria to integrate MRI into the diagnostic criteria, such that different lesions found by MRI could qualify for the dissemination in space—separated by space—as well as the dissemination in time, different episodes over time. These are criteria that are at the core of the multiple sclerosis diagnostic criteria.
The most recent iteration of the McDonald criteria, the 2017 McDonald criteria, have further refined these diagnostic criteria. They have further clarified how to use the MRI and have also brought back the importance oligoclonal bands. Oligoclonal bands, which are measured in the spinal fluid, aren’t required for the diagnosis of MS. However, now they can be used to fulfill the dissemination in space criteria that formally were allowed to be fulfilled only by either clinical criteria or MRI.
Fred D. Lublin, MD: The last 2 revisions of the McDonald criteria, the 2010 and 2017 criteria, have made it easier to diagnose MS. They’ve made it easier to meet criteria for dissemination in time. For example, you can now make a diagnosis on a single MRI scan, at least as a surrogate for dissemination in time. By doing that, and by codifying dissemination in space, it has taken a lot of people who used to be recognized to have clinically isolated syndrome [CIS] and is saying, “You now meet diagnostic criteria.”
For 2017 specifically, the major change was the addition of oligoclonal bands in the spinal fluid substituting for dissemination in time. If someone had a clinical attack, a typical CIS—optic neuritis, brain stem cerebellar inflammatory syndrome, or a partial myelitis—and their MRI met dissemination in space, and if they had oligoclonal bands, you could make a diagnosis of multiple sclerosis.
The revised guideline has led to earlier treatment. It hasn’t really altered how we treat people who are already diagnosed. It does raise a different issue, and that is that one has to be very careful about misdiagnosis. As a community, this is something we’re addressing more and more. There have been a number of important papers discussing this, because the downside of early diagnosis is misdiagnosis. We’ve stressed to the community that we want to treat MS as early as possible but not earlier. So one has to be careful when you’re making these early diagnoses that you have good certainty. The 2017 criteria provide that, but one has to remember that the McDonald criteria are for diagnosing multiple sclerosis, not for differentially diagnosing multiple sclerosis.