10 Essential Facts About Primary-Progressive MS

With only one FDA-approved drug available for PPMS, this type of multiple sclerosis remains difficult to treat, but adaptive devices and wellness programs can help you manage your symptoms.

mature woman speaking with her doctor
Primary-progressive MS differs from other forms of MS in significant ways.Getty Images

For many people with multiple sclerosis (MS), treatment is focused on preventing and managing relapses — acute symptoms that are often absent for long stretches of time. Ultimately the disease can result in disability in walking, thinking, and working.

But in people with primary-progressive MS (PPMS) — a small subset of the overall MS population — there is no initial relapse that heralds the onset of the disease, just a gradual appearance of symptoms. This can make PPMS more difficult to identify than so-called relapsing-remitting MS (RRMS). To make matters more difficult, out of over 20 disease-modifying treatments currently available for MS in the United States, only one is approved for PPMS.

Despite the challenges that PPMS presents, great strides have been made in its treatment and management. Here are 10 things you should know about PPMS.

1. There’s Often No Easily Identifiable Pattern of Symptoms in PPMS?

While relapsing forms of MS tend to cause an?acute neurological episode that’s hard to ignore, the onset of PPMS “is much more gradual and insidious,” according to Patricia K. Coyle, MD, a neurologist and the director of the multiple sclerosis comprehensive care center at Stony Brook University School of Medicine in Stony Brook, New York.

Classic symptoms of PPMS, according to Dr. Coyle, include difficulty walking, leg weakness, and muscle spasticity. But because the onset of these symptoms is gradual, “People are more apt to write it off as, ‘I’m getting older, I’m getting clumsier,’” she says. “I think it’s very easy to miss it for a period of time.”

While symptoms vary from person to person, other potential signs of PPMS, according to Johns Hopkins Medicine, are:

  • Pain, including headaches
  • Numbness
  • Lhermitte sign, or electric-like impulses that shoot down your back and legs when you bend your neck
  • Vision issues
  • Difficulty with balance
  • Dizziness
  • Depression or mood changes
  • Bladder and bowel control problems
  • Sexual issues
PPMS can also affect?cognitive function. Research has found that people with PPMS consistently experience more severe cognitive issues than people with RRMS, and that people with PPMS may need management strategies that specifically address cognitive impairment.

On the list of symptoms that may go unnoticed is a reduced sense of smell. According to one study, 84 percent of participants with PPMS were found to have an impaired sense of smell, compared with just 31 percent of those with relapsing-remitting MS.

2. It’s Unclear Exactly What Causes PPMS

According to Coyle, PPMS is believed to be the result of injury to the myelin that surrounds axons in the brain and spinal cord, as well as to the axons themselves. This neurodegeneration tends to affect all?people with MS over time, but it’s unknown why people with PPMS rarely experience the focal inflammation that causes acute symptoms typical of people with relapsing forms of MS.

“Whether there’s a fundamental difference between primary-progressive MS and relapsing MS is not clear,” says Coyle.

According to the National Multiple Sclerosis Society (NMSS), people with PPMS tend to have fewer brain lesions, with fewer inflammatory cells, than people with relapsing MS — which may account for the differences in symptoms. But people with PPMS also tend to have more spinal lesions than brain lesions.

There are certain genetic and environmental factors associated with the risk of MS, but none of them have been shown to predict the type of MS someone develops.

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3. PPMS Affects Only About 15 Percent of People With MS

Estimates of the prevalence of PPMS among all people with MS range from about 10 to 15 percent, according to Coyle. The NMSS puts the number at approximately 15 percent.

Unlike relapsing forms of MS, which are 2 to 3 times more likely to affect women,?PPMS affects the two sexes about equally, according to Johns Hopkins Medicine.

4. The Onset of PPMS Tends to Occur Later Than Relapsing Forms of MS

People with PPMS tend to be older than those with relapsing MS; the average?age of diagnosis is about 10 years later, according to the NMSS.

While the reason for this later onset isn’t fully understood, Coyle says it may reflect neurodegeneration (degeneration of the nervous system) that shows up clinically at midlife, when there has been a certain amount of loss of central nervous system function.

5. People With PPMS Can Stabilize for Up to Several Years

In some people with PPMS, Coyle says, the gradual worsening of symptoms that characterizes this form of the disease will abate for up to a few years, for unknown reasons. Sometimes, she says, “You can even see little blips of improvement,” but inevitably this improvement is reversed, and a person’s neurological deficit worsens.

Even when a person with PPMS appears to be clinically stable in terms of symptoms, Coyle says,?MRI scans typically show continuing damage to their central nervous system.

6. There Is Now an FDA-Approved Drug to Treat PPMS

In March 2017, the U.S. Food and Drug Administration (FDA) approved?Ocrevus (ocrelizumab)?as the first disease-modifying drug for PPMS.

Ocrevus was initially available only as an intravenous (IV) infusion, typically given about every six months after the first infusion, which is administered as two separate infusions two weeks apart. However, in September 2024 the FDA?approved a subcutaneous version of ocrelizumab called Ocrevus Zunovo. The twice-a-year, under-the-skin dosing regimen gives people living with MS another treatment delivery option. Ocrevus also is approved for relapsing forms of MS.

According to a clinical trial study, Ocrevus was found to reduce disability progression in people with PPMS compared with a placebo (inactive treatment).

The total volume of brain lesions after 120 weeks was also shown to shrink by an average of 3.4 percent in participants receiving Ocrevus, compared with an increase of 7.4 percent in those receiving the placebo.
A long-term follow-up study?showed that patients with PPMS who received Ocrevus early and continuously experienced lasting benefits when it came to slowing disease progression.

7. Ocrevus May Not Work Well in Everyone With PPMS

While the overall effectiveness of Ocrevus for PPMS has been demonstrated, the clinical trial study focused on younger people (age 55 or under) with more inflammatory disease activity. Coyle notes that although Ocrevus is sometimes prescribed to people older than 55, its effectiveness has not yet been proven in this age group, and more research is needed in this area. One study suggests extending its use to those under 65.

Taking Ocrevus if you’re older than 55 can come with risks, adds Coyle, who says Ocrevus is known to suppress the immune system. Those who take it are often more vulnerable to infections, which could pose additional risks in older people. “We know that as the body ages, the immune system ages, and you’re more likely to see things go awry,” she explains.

Additionally, the?FDA notes that clinical trials showed Ocrevus tended to work similarly for both men and women with RRMS but better in men with PPMS.

8. Even With Treatment, PPMS Leads to Gradual Loss of Neurological Function

Progressive forms of MS, including PPMS, are considered more severe than relapsing-remitting MS because they inevitably lead to disability, according to Coyle. “Once a patient enters or is in a progressive stage,” she says, “there is going to be gradual deterioration.”

In one study researchers found that out of a group of 853 participants with PPMS from 24 countries, 17 percent had mild disability, 44 percent had moderate disability, and 39 percent had severe disability. Disability in each group tended to progress significantly over 10 years.

Another study showed that, among patients with PPMS, factors that were associated with quicker disability progression included older age at PPMS onset and presence of disease activity.

9. It’s Important to Treat Symptoms of PPMS, Not Just the Disease Process

While there’s only one disease-modifying treatment with a modest benefit for PPMS, Coyle emphasizes that neurologists can still do a lot to help people with the condition manage their symptoms and improve their quality of life.

This means, according to Coyle, treating any spasticity, cramps, or pain, and talking about adaptive devices and behaviors to make daily tasks less arduous.

One type of adaptive device Coyle recommends is an all-terrain mobility chair, which can allow you to maneuver over rocky terrain, go up and down steps, or travel in other areas that might not be suitable for a normal wheelchair.

Another option is a smart-watch alert system. “For people with fairly significant gait impairment, this could actually notify people about a fall. They may be able to press an alert button. You could even have some smart-watch apps that will call in or check on individuals,” she explains.

10. Attention to Overall Wellness May Help Slow the Progression of PPMS

Coyle notes that in recent years it’s become increasingly clear how important a general wellness program is for people with PPMS. She emphasizes how important it is not to smoke, to maintain a healthy body weight, to do regular exercise, and to make sure you’re not deficient in vitamin D.

The NMSS also recommends various types of rehabilitation — including physical therapy, occupational therapy, and cognitive rehabilitation — to help preserve and better daily function among people with all types of MS.

The Takeaway

Primary-progressive MS, which affects up to 15 percent of people with MS, can be more difficult to diagnose and to treat than the relapsing form of the condition. While it can be challenging to manage, addressing the symptoms and maintaining your overall health may help slow the progression.

Additional reporting by Christina Vogt.

Editorial Sources and Fact-Checking

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Sources

  1. National Multiple Sclerosis Society. Primary Progressive Multiple Sclerosis.
  2. Primary Progressive Multiple Sclerosis. Johns Hopkins Medicine.
  3. Andreas J et al. Distinct Cognitive Impairments in Different Disease Courses of Multiple Sclerosis—A Systematic Review and Meta-Analysis. Neuroscience & Biobehavioral Reviews. December 2017.
  4. Schmidt FA et al. Olfactory Dysfunction in Patients with Primary Progressive MS. Neurology: Neuroimmunology and Neuroinflammation. June 14, 2017.
  5. Primary Progressive Multiple Sclerosis. National Multiple Sclerosis Society.
  6. Types of MS. National Multiple Sclerosis Society.
  7. FDA Approves New Drug to Treat Multiple Sclerosis. U.S. Food and Drug Administration. March 29, 2017.
  8. Montalban X et al. Ocrelizumab Versus Placebo in Primary Progressive Multiple Sclerosis. The New England Journal of Medicine. January 19, 2017.
  9. Wolinsky JS et al. Long-Term Follow-Up From the ORATORIO Trial of Ocrelizumab for Primary Progressive Multiple Sclerosis: A Post-Hoc Analysis From the Ongoing Open-Label Extension of the Randomised, Placebo-Controlled, Phase 3 Trial. The Lancet Neurology. October 29, 2020.
  10. Chisari CG et al. Effectiveness of Ocrelizumab in Primary Progressive Multiple Sclerosis: A Multicenter, Retrospective, Real-world Study (OPPORTUNITY). Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics. August 23, 2023.
  11. Drug Trials Snapshot: Ocrevus. U.S. Food and Drug Administration. April 18, 2017.
  12. Signori A et al. Long-Term Disability Trajectories in Primary Progressive MS Patients: A Latent Class Growth Analysis. Multiple Sclerosis. April 2018.
  13. Marrodan M et al. Disease Activity Impacts Disability Progression in Primary Progressive Multiple Sclerosis. Multiple Sclerosis and Related Disorders. December 11, 2019.
  14. Rehabilitation. National Multiple Sclerosis Society.
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Jason Paul Chua, MD, PhD

Medical Reviewer
Jason Chua, MD, PhD, is an assistant professor in the Department of Neurology and Division of Movement Disorders at Johns Hopkins?School of Medicine. He received his training at the University of Michigan, where he obtained medical and graduate degrees, then completed a residency in neurology and a combined clinical/research fellowship in movement disorders and neurodegeneration.

Dr. Chua’s primary research interests are in neurodegenerative disease, with a special focus on the cellular housekeeping pathway of autophagy and its impact on disease development in diseases such as Parkinson disease. His work has been supported by multiple research training and career development grants from the National Institute of Neurological Disorders and Stroke and the American Academy of Neurology. He is the primary or coauthor of 14 peer-reviewed scientific publications and two peer-reviewed online learning modules from the American Academy of Neurology. He is also a contributing author to The Little Black Book of Neurology by Osama Zaldat, MD and Alan Lerner, MD, and has peer reviewed for the scientific journals Autophagy, eLife, and Neurobiology of Disease.

Quinn Phillips

Author

A freelance health writer and editor based in Wisconsin, Quinn Phillips has a degree in government from Harvard University. He writes on a variety of topics, but is especially interested in the intersection of health and public policy. Phillips has written for various publications and websites, such as Diabetes Self-Management, Practical Diabetology, and Gluten-Free Living, among others.

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