10 Essential Facts About Primary-Progressive MS

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. To make matters more difficult, out of the 23 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. In a review article published in December 2017 in the journal Neuroscience & Biobehavioral Reviews, researchers found that people with PPMS consistently experienced 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 a study published in June 2017 in the journal Neurology: Neuroimmunology & Neuroinflammation, 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.

As noted in an article published in May 2017 in the journal Frontiers in Neurology, there are certain genetic factors associated with the risk of MS, but none of them have been shown to predict the type of MS someone develops. According to the same article, factors like age and Epstein-Barr virus (EBV) infection may also be risk factors for PPMS, though more research is needed on the potential link between EBV and PPMS.

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 two to three times more likely to affect women, PPMS affects the two sexes about equally, according to the NMSS.

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 is given as an intravenous (IV) infusion, typically about every six months after the first infusion, which is administered as two separate infusions two weeks apart. It’s also approved for relapsing forms of MS.

According to a study published in January 2017 in the New England Journal of Medicine, Ocrevus was found to reduce disability progression in people with PPMS compared with a placebo (inactive treatment). For example, by week 120 of the study, performance on a timed 25-foot walking test had worsened in 39 percent of participants receiving Ocrevus, compared with 55 percent of those receiving the placebo.

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 published in the Lancet Neurology in December 2020 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 January 2017 study focused on younger people (age 55 or younger) 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.

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, according to Coyle, a later analysis requested by the FDA showed that Ocrevus tended to work better in men than in women.

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 a study published in April 2017 in Multiple Sclerosis Journal, 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, published in Multiple Sclerosis and Related Disorders in December 2019, 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, Coyle explains, can allow you to maneuver over rocky terrain, go upstairs, 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.

Additional reporting by Christina Vogt