Why do some people with multiple sclerosis (MS) feel worse over time, even when their MRIs show no changes?
Living with multiple sclerosis (MS) can feel like a journey full of unexpected twists and turns. For many, the focus has traditionally been on relapses—those sudden flare-ups—and changes seen on MRI scans. But what about the slow, steady worsening of symptoms that can happen even when MRIs look stable? This is where smoldering MS comes into the picture—a term that’s helping to explain why some people with MS feel worse over time, even without relapses or new lesions.
Recently, I had the privilege of sitting down with Dr. Gabriel Pardo, a physician and researcher at the Oklahoma Medical Research Foundation’s MS Center of Excellence. Dr. Pardo is deeply involved in both patient care and clinical research, working to improve how we understand and treat MS. His expertise and dedication to helping people with MS made this conversation truly enlightening and I can’t wait to share what we discussed.
So without any further introduction, let’s discuss my conversation with Dr. Pardo where we explored what smoldering MS means, how it affects individuals, and what it could mean for future treatments.
Smoldering MS refers to a gradual worsening of symptoms that happens without the dramatic inflammation typically seen in MS relapses. While relapses are like sudden storms—causing visible damage and often showing up on MRI scans—smoldering MS can be described more like a slow burn. It involves ongoing low-level inflammation and damage in the brain that can lead to a steady decline in physical or cognitive abilities.
When I first sat down with Dr. Pardo, he explained that even when relapses are under control and MRI scans show no new activity, many people still notice they’re not functioning as well as they used to.
They might find it harder to walk, climb stairs, or concentrate at work. This slow decline is now recognized as progression independent of relapse activity (PIRA), and it’s an area where current treatments don’t work as well. However, with growing research into smoldering MS and promising new therapies on the horizon, there’s hope that better solutions are on their way.
The exact causes of smoldering MS are still being studied, but Dr. Pardo highlights two main factors:
Other contributors include clusters of immune cells forming in the brain’s protective layers, which can harm nearby tissue over time. While these processes are challenging to fully control with current treatments, ongoing research, and advancements—like the development of BTK inhibitors—offer hope for therapies that could better target this smoldering inflammation and improve outcomes for people living with MS.
For those living with smoldering MS, it can be deeply frustrating. Many report feeling worse each year despite being told their disease is “stable.” Dr. Pardo and I both want to emphasize how important it is to validate these experiences, no matter when you are feeling them.
He shared a quote with me I felt really compelled to share: “Patients tell me they thought it was all in their head—and well, it is in your head; that’s where MS is—but you’re not making it up.”
Having a name for this process—smoldering MS—can be empowering. It helps those experiencing smoldering understand that their symptoms are real and not their fault. As one patient put it during our discussion: “If you can tell me there’s a name for something, I’m so much less likely to feel like it’s all in my head.”
This is truly the first step toward taking back control of your life. Like I always say, you are in the driver’s seat of MS, not the other way around.
Currently, most treatments for MS focus on stopping relapses and preventing new damage seen on MRIs. Unfortunately, these therapies are less effective at addressing smoldering inflammation. However, new treatments are being developed to target this specific issue.
One promising option is Bruton’s tyrosine kinase (BTK) inhibitors—a type of medication currently in clinical trials. These drugs aim to tackle both types of inflammation: the sudden kind that causes relapses and the slow-burning kind linked to smoldering MS. If successful, BTK inhibitors could become an important tool for managing both aspects of the disease.
Dr. Pardo’s excitement about these developments is really promising, but he did express that more research is needed. Results from clinical trials are expected as early as 2025, something I will provide an update on as soon as I see developments.
If you’re experiencing symptoms that seem to be worsening despite stable MRIs or no recent relapses, there are steps you can take:
The recognition of smoldering MS marks an important step forward in understanding this complex disease. By naming and studying this process, researchers and doctors can work toward better treatments that address not just relapses but also the underlying causes of progression.
As Dr. Pardo put it: “This isn’t something you’re imagining—it’s real.” For people living with MS, having their experiences validated and understood is a critical part of receiving better care.
Whether it’s through new medications or simply raising awareness about smoldering MS, progress is being made—and that’s something worth holding onto.
If you are curious to keep up to date with the latest information, treatments, and strategies to manage MS symptoms, my podcast – The MSing Link – is the best source of information for staying informed. I partner with so many incredible specialists (like Dr. Pardo) to break down what you are experiencing, how to find relief, and to get your questions answered. Most importantly, I emphasize in every video that you are not alone and have resources available to support you.
Do you have any further questions about smoldering in Multiple Sclerosis? Please feel free to DM me on Instagram @doctor.gretchen.
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Dr. Gretchen Hawley's The MSing Link offers a comprehensive guide to taking control of your MS symptoms and improving your mobility through MS-specific exercises and strategies.
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As a physical therapist & Multiple Sclerosis Certified Specialist, I have spent the last 10 years teaching people with MS how to feel more confident & empowered through MS-specific exercises and strategies.
If you want support and encouragement, plus a healthy dose of tough love, come follow me on Instagram (@doctor.gretchen) or on YouTube @DoctorGretchenHawley. It's where I share daily tips, tricks, and information about new offers — plus, you’re bound to feel more empowered, hopeful, & motivated after watching each post and video!
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