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The Latest About Multiple Sclerosis

Cedars-Sinai Experts Discuss the Role of Leading-Edge Imaging in Diagnosing, Tracking and Finding New Treatments for the Chronic Inflammatory Component of the Disease

Two leading multiple sclerosis (MS) experts—Nancy Sicotte, MD, chair of the Department of Neurology and director of Multiple Sclerosis and Neuroimmunology at Cedars-Sinai, and Pascal Sati, PhD, director of the Neuro Imaging Program in the Department of Neurology and associate professor of Neurology and Biomedical Sciences at Cedars-Sinai—are attending the Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2024 Feb. 29-March 2 in West Palm Beach, Florida, where their teams will present research on leading-edge MS imaging techniques.

Multiple sclerosis is a disease of the brain and spinal cord in which the body’s immune system attacks the protective sheaths that surround nerves, disrupting communication between the brain and the rest of the body. Brain imaging, which allows physicians to see the lesions that form at the point of attack, is essential for diagnosing the condition and guiding patient treatment.

Sicotte and Sati are among co-authors of a consensus statement from the North American Imaging in MS Cooperative that seeks to standardize imaging techniques for identifying chronic active lesions, an important indicator of chronic brain inflammation in MS. The statement, published in the peer-reviewed journal Brain, is designed to set guidelines for imaging chronic active lesions and how imaging will be used for diagnosis, predicting patient outcomes, and clinical trials.

They recently spoke with the Cedars-Sinai Newsroom about the role of imaging in MS today and in the future.

How has imaging changed treatment for patients with MS?

Nancy Sicotte, MDSicotte: When I started treating patients with MS more than two decades ago, there were essentially no treatments, and now we have more than 25. One of the reasons we have these medications is because of advancements in the use of MRI to track disease activity in the brain and spinal cord of people who have MS. Because MRI is more sensitive than clinical attacks, it became a powerful tool to test the effectiveness of new therapies, and that energized research and led to the development of a whole suite of new MS treatments that decrease the likelihood of new lesions appearing.

How do lesions appear on an MRI?

Sicotte: In patients with active MS, the blood-brain barrier, which keeps potentially harmful substances from reaching the brain, breaks down due to immune activation. This results in what we call a contrast-enhancing lesion, the classic acute inflammatory lesion. These lesions show up as bright spots that are easily detected using MRI after injection of contrast. Over time, the blood-brain barrier repairs itself and leaves behind a chronic lesion that is akin to a scar that can also be tracked over time using dedicated MRI techniques.

What are the newest lesions that have been identified?

Pascal Sati, PhDSati: We and others have recently identified a new type of lesion, called a paramagnetic rim lesion, that we think is an indicator of chronic brain inflammation that may be the primary driver of disease progression in treated patients who do not have acute inflammatory lesions.

In paramagnetic rim lesions, microglia, the primary immune cells that respond to tissue injury and clean up debris in the brain, form a rim around lesions where the blood-brain barrier has healed. This is a sign that the inflammation is persisting at low intensity behind a closed blood-brain barrier. The rims are like a smoldering fire that continues to burn and slowly propagate. MS patients with a lot of paramagnetic rim lesions are more likely to have increased disability, so we think the lesions might be a good biomarker for progressive disease. Because our current therapies can’t cross a closed blood-brain barrier, we don’t have a way to treat these lesions at present.

Can advanced imaging techniques help identify therapies to treat chronic inflammation in MS patients?

Sati: We think so! We have received funding from the National Multiple Sclerosis Society and the National Institutes of Health to evaluate paramagnetic rim lesions as a diagnostic biomarker using detection techniques we developed. We are now exploring novel techniques to measure the amount of chronic inflammation and tissue damage in these lesions to evaluate the effects of new brain-penetrant therapies. We hope that these new quantitative techniques combined with AI will enable us to measure paramagnetic rim lesions in a fast, efficient way that could be put into practice in most imaging facilities and be deployed in clinical trials.

We’re doing this work in collaboration with all the stakeholders: the MRI physicists at our institution, the MRI vendors that provide the scanners and imaging technology, the neuroradiologists who read these scans, and the pharmaceutical industry that develops the therapies. We hope to prove that our concepts can be applied on different MRI scanners, so that they can be used in international clinical trials testing new therapies that can target these lesions and change the course of the disease.

What are your hopes for the future of MS care?

Sicotte: We're really lucky here at Cedars-Sinai. We have a large group of patients who are eager to participate in research, and we have been collecting MRI data over many years. Added to that, we're employing these newer techniques. We're hoping that the data we are collecting will tell us more about the drivers of progressive disease, how to predict which patients might not require treatment, and which we should treat aggressively from the outset.

Read more on the Cedars-Sinai Blog: Cedars-Sinai Neurology Chair Honored by National MS Society for COVID-19 Work