In April 2022, numerous presentations at the American Academy of Neurology (AAN) Annual Meeting provided data on the newest and most up-to-date 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 this data reflects the shift in the field toward a more granular look at disease and its underlying mechanisms. As more effective treatments have come to market, MS specialists have begun to question what is the optimal therapeutic approach 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 how the medical field views MS. He developed a topographic model of the disease in an effort to better understand the so-called phases of MS and whether they overlap in ways previously unknown.
In a conversation with NeurologyLive®Krieger shared his thoughts on ongoing conversations and trends in MS, highlighting how new therapies partly reflect this shift in thinking about the underpinnings of the disease and what could be done with behavioral approaches to help patients. to meet the challenges they face.
NeurologyLive®: How have the conversations about MS changed, especially with regards to these new therapies being developed?
Stephen Krieger, MD: Well, I think we’re starting to understand better what processes cause accumulation of disability, recognizing as we do in MS, that most disability doesn’t just come from relapses. With relapses, we all know how to see them, we know how to assess them with MRIs and with conventional scanners. And I think that’s part of the movement in our field to look a little below the surface, to look below the threshold, to use a language that I often talk about with my topographical model. It’s how can we look beneath the surface of what we regularly see and shed light on the drivers of disease mechanisms. Activated microglia seem to play a big role in this, and all new generations of therapies are going to be looked at to see how well they block this.
Other big topics of conversation are diet, wellness and depression. What was discussed in this area that interests you?
If we start from a modern, and maybe a bit esoteric, perspective looking at activated microglia and the things that we can’t do in routine clinical practice, I think it’s nice to focus about the things we can do in our routine clinical practice that have been shown to make a difference. My colleague James F. Sumowski, PhD, at Mount Sinai, worked with my other colleague, Ilana B Katz Sand, MD, on reviewing the Mediterranean diet and the correlation between adherence to a Mediterranean diet – the MIND diet and disability measures. on the functional composite, correlated with patient-reported disability outcomes, and even measures of brain atrophy. Here they show, with a cohort of around 600 patients, that better adherence to the MIND diet and the Mediterranean diet had beneficial effects on measurable disability, patient-reported disability, and brain atrophy.
Also, just to take stock, this is something we can all do. We can all recommend a Mediterranean diet. It is not necessarily very expensive or very exclusive. He is really trying to move away from processed foods and into a much more natural way of eating. We can even measure brain atrophy as Dr. Katz and Dr. Sumowski did. It was of third ventricular width. We don’t even need a sophisticated, quantified MRI for that. You can just measure the third ventricle. It is therefore a very accessible means of evaluating the impact of a very feasible intervention, the Mediterranean diet.
The other thing that was presented here from this same cohort, the Sumowski cohort at Mount Sinai, was presented by one of my research collaborators, Tali R. Sorets, who was looking at depression. We focus on symptom management, quality of life and MS, but they hypothesize that the way depression behaves in MS is different from ‘ordinary’ depression, so to speak. They hypothesize that because of the inflammatory mechanisms that can cause depression in MS, it could have a particular effect on it: anhedonia, loss of pleasure. This is what they found using a sort of complex network analysis of various neuroscience tests. People with MS may not endure sadness, which I think for most clinicians is what we think is the main calling card of depression. But they may have actually lost the sense of fun, that anhedonic feeling undermining agency people. And it is difficult to intervene there because it can be very self-perpetuating. So they are looking for ways to try to solve this problem. The MIND diet, again, has been shown to have beneficial effects on depression outcomes, so this is one way to tie it all 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 merging these new therapies with these other wellness approaches?
I think our field of MS has really moved in that direction not only to very effective drugs to prevent relapses and damage, but also to ways of trying to maximize brain reserve. That’s what my colleagues and Sumowski really focus on. This relates directly to how I view multiple sclerosis with the notion of lesions in their various places 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 no matter how deep the reserve reservoir is, it helps to keep disease compensated below the surface. I think the future of MS care won’t just be the optimal disease-modifying therapies, but all of these more holistic techniques for keeping the reservoir full, keeping the reserve – the positive behaviors related to brain health that we can help our patients achieve. I think this combination is what will ensure good results in this disease.
Transcript edited for clarity.