Silent Progression in Multiple Sclerosis: What every person living with MS needs to know

People living with MS must understand that the disease can progress quietly and without obvious symptoms — even if relapses and lesions are managed.

Multiple sclerosis (MS) is currently categorized into different types based on disease presentation and disease course. These subtypes include: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS).1

But growing evidence suggests that MS progression occurs no matter what type you have, and that it happens independent of relapses or other disease activity.2,3,4

“The distinction between relapsing and progressive subtypes of MS is overstated,” says Dr. Jiwon Oh, a neurologist and medical director of the Barlo Multiple Sclerosis Centre at St. Michael's Hospital in Toronto. “The intense relapses seen in RRMS mask the slower, less obvious background symptoms of progression that can often happen even in early RRMS. Now that we have treatment plans that effectively manage relapses, the progressive characteristics of MS are easier to see.”

This is important news for patients, doctors and anyone touched by MS, as it affects how to approach one’s lifestyle, disease management and treatment plans.

Adra's Story

MS turned Ardra Shephard’s life upside down at age 23. She was diagnosed with RRMS in 2001, decades before it was understood that progression happens even without relapses. As recommended by specialists, she advocated for herself to find answers and pursue the right treatment plan for her. As time went on, her minimal relapses and no new lesions showing on her MRI reports led specialists to tell her she was doing “great.” 

“It can really get in your head, this idea of relative stability when those symptoms resolve,” Ardra says. She didn’t know it at the time, but signs of progression were slowly accumulating, ultimately affecting her mobility.

She was used to pushing her physical limits at the gym and measuring the results. “I noticed my foot starting to trip when running on the treadmill, at the 45-minute mark. Then at 30. Then 20,” she remembers. “Back then, if your MS doctor heard you could run for 45 minutes they’d say, ‘Amazing, you’re killing it!’”

The slow deterioration of these treadmill runs should have been flagged as a sign of disease progression, but Ardra didn’t know what it meant at the time. There’s a phrase for it now, and it’s an important part of the modern MS vocabulary: progression independent of relapse activity, or PIRA.

Ardra celebrating her 20th wedding anniversary in Paris. SUPPLIED.

A key term in MS care today: PIRA5,6

“I describe PIRA as some sort of functional limitation that clearly gets worse year after year,” says Dr. Oh. “A standard neurologist's exam won’t always detect progression, because it is very slow and subtle. I need patients to tell me, so I’ll ask them questions like, ‘Do you notice you're not getting work assignments in on time? Any differences in physical activities like your ability to hike, run or lift weights? Is fatigue getting to the point where it's actually impairing your ability to work or to engage in leisure or personal activities?’”

Both people living with MS and their doctors need to understand PIRA. For patients, it can make certain aspects of MS less confusing. If a patient knows that they are not just battling relapses but also progression, they may consider different lifestyle or treatment plans.

For doctors, it’s important to probe for evidence of PIRA as the typical neurological exam often can’t detect PIRA, and to take any observations about changes in functionality seriously, even if they seem minor. Charting the progressive signs of MS can both help current patients and contribute to the wider understanding of PIRA.

Understanding MS progression matters

People living with MS must understand that they will very likely face both relapses and progressive symptoms, possibly at the same time. The old way of thinking suggested that these challenges may occur separately, or that progression was only related to having relapses. This is no longer the case. Progression happens from the very beginning, but it can be very hard to detect and varies widely between patients.

This view of MS as progressive from the beginning places even more importance on patients having informed discussions with their health-care team. For people who have lived with the condition for years, and for those newly diagnosed: preserving brain health is a top priority in MS.

“You can't undo brain damage,” says Ardra. “You have to act fast, you have to consider your risk tolerance, lifestyle and where you’re at in life. It’s also really important to know that you're not married to your treatment plan. Reevaluate if something isn't working for you and have these conversations with your doctor.”

In addition to medication, Dr. Oh emphasizes that there are many lifestyle strategies to consider. “Maintaining excellent physical and mental health, things like leisure activities and strong social connections: all of these can be equally important in terms of the chronic care plan7,8,” she says.

Talk to your health-care team about what MS progression and PIRA means for you. A tool like LiveYourLifeMS.ca can help you frame this discussion with your health-care team.

Ardra at her book tour reading at the Sunshine Coast Festival in Seychelt, BC. SUPPLIED.

Understanding MS progression matters

People living with MS must understand that they will very likely face both relapses and progressive symptoms, possibly at the same time. The old way of thinking suggested that these challenges may occur separately, or that progression was only related to having relapses. This is no longer the case. Progression happens from the very beginning, but it can be very hard to detect and varies widely between patients.

This view of MS as progressive from the beginning places even more importance on patients having informed discussions with their health-care team. For people who have lived with the condition for years, and for those newly diagnosed: preserving brain health is a top priority in MS.

“You can't undo brain damage,” says Ardra. “You have to act fast, you have to consider your risk tolerance, lifestyle and where you’re at in life. It’s also really important to know that you're not married to your treatment plan. Reevaluate if something isn't working for you and have these conversations with your doctor.”

In addition to medication, Dr. Oh emphasizes that there are many lifestyle strategies to consider. “Maintaining excellent physical and mental health, things like leisure activities and strong social connections: all of these can be equally important in terms of the chronic care plan7,8,” she says.

Talk to your health-care team about what MS progression and PIRA means for you. A tool like LiveYourLifeMS.ca can help you frame this discussion with your health-care team.

References:

1  Types of MS. MS Canada. Available at: https://mscanada.ca/intro-to-ms/types-of-multiple-sclerosis 

2 Kuhlmann T, Moccia M, Coetzee T, et al. Multiple sclerosis progression: time for a new mechanism-driven framework. Lancet Neurol. 2023;22(1):78-88. doi:10.1016/S1474-4422(22)00289-7 

3 Krieger S, Cook K, Hersh CM. Understanding multiple sclerosis as a disease spectrum: above and below the clinical threshold. Curr Opin Neurol. 2024;37(3):189-201. doi:10.1097/WCO.0000000000001262

4 Ganjgahi H, Häring DA, Aarden P, et al. AI-driven reclassification of multiple sclerosis progression. Nat Med. 2025;31(10):3414-3424. doi:10.1038/s41591-025-03901-6

5 Fuchs TA, Schoonheim MM, Zivadinov R, et al. Cognitive progression independent of relapse in multiple sclerosis. Mult Scler. 2024;30(11-12):1468-1478. doi:10.1177/13524585241256540

6 Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145(9):3147-3161. doi:10.1093/brain/awac016

7 Physical Activity and MS. MS Canada. Available at: https://mscanada.ca/physical-activity-and-ms 

8  Latinsky-Ortiz EM, Strober LB. Keeping it together: The role of social integration on health and psychological well-being among individuals with multiple sclerosis. Health Soc Care Community. 2022;30(6):e4074-e4085. doi:10.1111/hsc.13800