The Future of Care and Focusing on Brain Health in MS to Maximize Reserve

Stephen Krieger, MD

In April 2022, numerous presentations at the American Academy of Neurology (AAN) Annual Meeting provided data on the latest and newest therapies and approaches in the treatment of multiple sclerosis (MS). Additionally, many of these presentations focused on the impact of behavioral strategies, such as diet, on disease progression.

Much of these data reflect the shift in the field toward a more granular look into the disease and its underlying mechanisms. As more efficacious therapeutics have been brought to the market, specialists in MS have begun to question what the optimal therapeutic approach is, and when certain aspects of the disease—particularly the neurodegenerative effects—begin to surface. Stephen Krieger, MD, professor of neurology, Icahn School of Medicine, and staff neurologist, Corinne Goldsmith Dickinson Center for MS, Mount Sinai, has long thought about the way the medical field views MS. He has developed a topographical model of the disease in an effort to better understand the so-called phases of MS and whether they overlap in a way previously not understood.

In a conversation with NeurologyLive^®, Krieger shared his thoughts on the ongoing conversations and trends in MS, pointing to how the new therapies partially reflect this change in thinking about the disease’s underpinnings, and what might be done with behavioral approaches to help patients address challenges they face.

NeurologyLive^®: How have conversations changed in MS, especially as it as it relates to these new therapeutics that are being developed?

Stephen Krieger, MD: Well, I think we're starting to get a better look at what are the processes that are causing accumulation of disability, recognizing as we do in MS, that most disability doesn't come from relapses alone. With relapses—we all know how to see them, we know how to assess them with MRI scans and with conventional scans. And I think this is part of the move in our field to look a little bit below the surface, to look under the threshold, to use language that I often talk about with my topographical model. It's how can we look under the surface of what we routinely see and shed light on drivers of disease mechanisms. Activated microglia seem like they're going to play a big role in this, and all of the new generation of therapeutics are going to be looked at to see how well they shut that down.

Other big areas of conversation are diet, wellness, and depression. What has been discussed in that realm that’s of interest to you?

If we go from a modern, and maybe a little bit esoteric, point of view with looking at activated microglia and things that we can't do in routine clinical practice, I think it's nice to move to a focus on things that we can do in our routine clinical practice that are being shown to make a difference. My colleague James F. Sumowski, PhD, at Mount Sinai, has worked with my other colleague, Ilana B Katz Sand, MD, on looking at the Mediterranean diet, and how adherence to a Mediterranean diet—the MIND diet—correlated with disability measures on functional composite, correlated with patient reported outcomes of disability, and even metrics of brain atrophy. Here, they're showing, with a cohort of around 600 patients, that better adherence to the MIND diet and Mediterranean diet had beneficial effects on measurable disability, patient-reported disability, and brain atrophy.

Also, just to make the point—this is something we can all do. We can all recommend a Mediterranean diet. It's not necessarily very expensive or very exclusive. It just really tries to get away from processed foods and to a much more natural way of eating. We can even measure the brain atrophy the way Dr. Katz and Dr. Sumowski did. It was with third ventricular width. We don't even need fancy, quantified MRI for that. You can just measure the third ventricle. So, it's a very accessible way of gauging the impact of a very attainable intervention, the Mediterranean diet.

The other thing that was presented here from that same cohort, Sumowski’s cohort at Mount Sinai, was presented by one of my research collaborators, Tali R. Sorets, looking at depression. We focus on symptom management and quality of life and MS, but they hypothesize that the way depression behaves in MS is different from “run of the mill” depression, so to say. They hypothesize that because of the inflammatory mechanisms that may cause MS depression, it could have a particular effect on it: anhedonia, loss of pleasure. That's what they found using kind of a complex network analysis of various neuroscience tests. It may not be the case that people with MS will endure sadness, which I think, for most clinicians, is what we think is the main calling card of depression. But they may actually have lost a sense of pleasure, this anhedonic feeling sapping people of agency. And it is hard to intervene there because it can be very self-perpetuating. So, they're looking at ways of trying to address that. The MIND diet, again, has been shown to have benefits on depression outcomes, so it's a way of kind of tying this whole piece together, at least coming out of our comprehensive care program at Mount Sinai.

What do you see for the future of the field, in terms of melding these new therapies with these other wellness approaches?

I think our field in MS has really moved in this direction of not just highly effective medicines to prevent relapses and lesions, but also ways of trying to maximize brain reserve. That's what my colleagues and Sumowski is really focused on. It speaks directly to the way I look at multiple sclerosis with the notion of lesions in their various locations causing symptoms. But the extent to which brain health is maintained allows us to compensate for them. In my topographical model, the notion is that however deep the pool of reserve is, it helps to keep the disease under the surface compensated for. I think the future in MS care is going to be not just optimal disease-modifying therapies, but all of these more holistic techniques to keep the tank full, keep reserve up—the positive brain-health-related behaviors that we can help our patients to achieve. I think that combination is what will ensure good outcomes in this disease.

Transcript edited for clarity.