ACTRIMS 2022 | Imaging biomarkers of RIS

RIS, or radiologically isolated syndrome, essentially refers to people who get an MRI for one reason or another and they have lesions on the MRI that look almost identical to what we see in people with MS, but they don’t have any current or prior symptoms that are typical for MS. And so, these people are a little bit difficult to manage clinically, because we don’t yet have clear evidence based guidelines as to what to do.

We do know that a large proportion of these people are at risk of eventually developing MS. At 10 years, the risk is cited to be a little bit over 50%. So, what do we do now? It really kind of depends on the center and the clinician, but most people follow these patients annually with a clinical exam and MRI. And, obviously, if they develop symptoms of MS, then you treat them as MS, but it gets challenging sometimes because some people will develop new lesions every year. Yet, you can’t really say that they have MS unless there are typical clinical symptoms.

But in some situations when there’s enough concern, I do think a number of clinicians treat just because, based on the evidence that we have in MS, we worry when there are so many new lesions that form every year. But this is why we actually need better prognostic biomarkers. And this is where I think some imaging techniques have a lot of potential.

In the clinical setting, we just have kind of typical MRIs of the brain and spinal cord. We do know, based on studies, that if you have a lesion in your spinal cord it increases your risk of developing MS. And so, obviously, if somebody has many risk factors this is when, as a clinician, you might get worried and even consider treatment, even if they don’t develop symptoms. But there are a number of emerging techniques that if they are validated in studies may be really useful. There’s a few of them I could name but one of them is something that I discussed in the presentation yesterday, which is the central vein sign. When you use different susceptibility based techniques, if a lesion has a central vein in the middle, you can identify it.

There’s also something called paramagnetic rim lesions, or PRLs that are supposed to represent chronic lesions that have active inflammation at the edge. And we know that in MS these are associated with more disability, as well as more progressive symptoms. And so, based on at least the small study that we did in RIS where we looked at central veins and PRLs, we found that there were strong correlations between these imaging findings, and cognitive deficits in RIS patients. And so, obviously, we need to look at this prospectively, but there is some suggestion that maybe having a large proportion of central veins, as well as PRLs is something that we can use to say that, say, an individual patient has a much higher risk of developing MS and so, they should be treated even when they are asymptomatic.

There’s people following RIS patients all over the world and at our center we also have a decent sized RIS cohort. And we’re following them longitudinally, looking at many of these imaging measures. So, I think the results of that will be helpful to determine if some of these imaging biomarkers have potential to prognosticate. And there are two Phase III clinical trials in RIS where the efficacy of dimethyl fumarate and teriflunomide are currently being evaluated. And there likely will be a readout very soon, maybe even within this calendar year for one of the studies, that’s DMF in RIS patients.