An Overview of Secondary Progressive Multiple Sclerosis (SPMS)

When you stop having relapses but your MS worsens

doctor talking with patient
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Maybe you've just been diagnosed with secondary progressive MS (SPMS). Or maybe you're one of the 85 percent to 90 percent of people with multiple sclerosis (MS) who are initially diagnosed with relapsing-remitting MS (RRMS) and you're not sure how your doctor will know when (or if) it transitions to secondary progressive MS (SPMS). Either way, it's good to understand how the disease can progress so you can be prepared for the future.


The majority of people with RRMS transition to SPMS, which is characterized by steadier progression of symptoms and disability with fewer or no relapses.

Before disease-modifying treatments (DMTs) became widely available, about 50 percent of people with RRMS eventually developed SPMS within 10 years and about 90 percent within 25 years. It's not yet clear what effect disease-modifying therapies have on MS progression, but experts hope that SPMS may be slower to develop in people who use them.

You can go from having RRMS to SPMS at any time, but the process is gradual and, in most patients, slow. In fact, there's often a gray zone between RRMS and SPMS when you're moving into the progressive phase of MS but are still having occasional MS relapses. Generally speaking, though, this transition occurs within 10 to 20 years after the onset of disease.

The average age for conversion to SPMS is 40 to 49 years old.

Signs and Symptoms

There aren't any guidelines or criteria that define when you move from RRMS to SPMS, but here are some signs that you and your doctor may look for when determining whether this transition is occurring or has already occurred.

Your Medications Don't Work Well

Sometimes, despite your best efforts and adherence to taking your disease-modifying medication, you may begin to show increasing disability without a corresponding increase in the number of lesions on your magnetic resonance imaging (MRI) scans. This could be an indication that you're moving into SPMS.

On the other hand, your medication not working may be due to another reason. For instance, if neutralizing antibodies to one of the interferon-based drugs are present, your neurologist may switch you to another one.

Some people worry that they're entering the progressive phase of MS because they stop having relapses. However, this could be a very good sign, as it could mean that your disease-modifying treatment is working.

Your Relapses Are Changing

The natural course of RRMS is for the number of relapses you have to actually decrease over time. However, the relapses that do occur may be more severe, bringing multiple symptoms, rather than just affecting one area of function.

Recovery from these relapses also tends to be incomplete, meaning that even after the acute phase of the relapse has passed, you still have some symptoms and/or disability. Additionally, you no longer respond as well (or possibly at all) to Solu-Medrol during these relapses.

There's a Large Amount of Damage Seen on MRI

When you have an MRI, you and your doctor may see these results:

Greater Lesion Burden

This means that there's a greater total number of lesions, which tend to be:

    • Around the ventricles (the cavities in the brain that are filled with cerebrospinal fluid)
    • Overlapping
    • Concentrated in the brainstem and spinal cord

More Axonal Damage and “Black Holes"

Areas that show up as dark (hypointense) spots on a T1 scan are referred to as “black holes.” These are areas where there has been repeated inflammation, leading to complete destruction of both myelin and the axons themselves. These areas strongly correspond to disability.

Enlargement of CSF-Filled Ventricles in the Brain

This is a measure of atrophy. As there is less brain tissue, the spaces around and within the brain get bigger.

A Decrease in Gadolinium-Enhancing Lesions

Paradoxically, the number of new, active gadolinium-enhancing lesions decreases in later stages of RRMS. This is because the disease is most likely becoming more degenerative than inflammatory.

You Have a Greater Degree of Disability

When measured by the Expanded Disability Status Scale (EDSS), people with RRMS tend to have a score of 4 or less. People with SPMS, on the other hand, usually have a score of 6 or higher, meaning that some form of assistance is needed to walk.

If you have RRMS and you reach a level of 4 to 5.5 on your EDSS, which is indicated by the inability to walk more than 500 meters without resting, this means you'll probably develop SPMS within a fairly short time period.

Your doctor will also find more abnormalities during your neurological exam. This shows that your brain can no longer compensate for the demyelination—your immune system's attacks on the myelin sheath, the protective covering around nerve fibers.

Lastly, people that develop SPMS tend to exhibit more cognitive impairment. This is most likely due to the greater degree of atrophy in the brain, which is highly correlated to cognitive dysfunction. What this really means is that your brain can't offset the damage anymore, especially where there's complete axonal (nerve fiber) destruction, resulting in black holes.


As with all types of MS, no one knows what causes SPMS. It's believed to be a combination of factors involving genetics and environmental triggers like infections, vitamin D deficiency, geography, and childhood obesity.

In terms of factors that may influence the transition from RRMS to SPMS, studies show that men appear to develop SPMS more quickly and at a younger age than women. However, both genders end up needing to use a cane at around the same age, so even though they may enter the progressive phase earlier, males don't have a worse outcome.

Smoking has also been found to increase your risk of transitioning from RRMS to SPMS.


If you've already been diagnosed with RRMS, you probably know that the diagnostic process can be a time-consuming process as your doctor performs tests, rules out other conditions, and puts together pieces of the diagnostic puzzle.

Similarly, diagnosing SPMS requires a combination of strategies, including a thorough neurological examination and repeat MRIs. As with RRMS, there are no definitive diagnostic tests.

When it comes to diagnosing SPMS, your doctor will need to confirm two facts:

  • You have a history of RRMS: In order to be diagnosed with SPMS, you must have had RRMS first. For some people, confirming this history may be difficult as they may have never realized they had RRMS, thanks to subtle symptoms or even misdiagnosis.
  • Your MS is now in a progressive state: Once your doctor confirms your RRMS history, he or she must confirm that your disease is progressive, which means that it's gradually getting worse.

Changes in SPMS

In RRMS, inflammatory processes cause demyelination. This inflammation can be seen on your MRIs during relapses in the form of bright white spots (gadolinium-enhancing lesions).

However, in SPMS, there's less inflammation and more degeneration of gray matter and white matter, as well as spinal cord atrophy (nerve damage and loss), which can also be seen on MRI. While there's still demyelination and inflammation happening, it's more widespread.

Spinal cord atrophy is far more prominent in SPMS than it is in RRMS too, and this nerve loss can cause bowel and bladder problems, along with more difficulty walking.

While you experienced relapses in RRMS, these will become less and less frequent. Instead, you'll notice that your condition is gradually worsening. For instance, you might be able to tell that it has gotten harder to walk for the last several months, but you can't pinpoint a time when it suddenly got worse.

The Transition Period

There's often a transition period between when RRMS ends and SPMS begins. This can make it tricky to tell exactly what's going on because there's overlap between the two types. As your MS progressively worsens, you may still have an occasional relapse.

Disease Modifiers

SPMS can also be classified throughout the course of the disease as active, not active, and with or without progression.

  • Active: You have relapses and/or new MRI activity.
  • Progression: There's evidence that your MS is getting worse.

So, for instance, if your SPMS is classified as not active without progression, it's stable. If it's active without progression, you've had relapses and/or new MRI activity, but there's no evidence that your disease is getting worse.

Like RRMS, SPMS symptoms are highly variable, and so is the rate at which it progresses. Every situation is different; some people become more disabled more quickly than others.


Treatment for SPMS is similar to that of RRMS, though progressive forms of MS are notoriously more difficult to treat.

Rehabilitation Therapies

If your MS is progressing, your neurologist will likely review your rehabilitation interventions with you to see if you need any adjustments or additions. These treatments, which include physical therapy, occupational therapy, speech-language therapy, and cognitive rehabilitation, can help you function at your best and maintain your muscle strength and mobility.

Drug-Modifying Therapies

Especially if you're still having relapses and/or new MRI activity, you can take any of the disease-modifying therapies (DMTs) that are used to treat RRMS. In fact, even if your SPMS isn't active, your doctor will likely have you keep taking whatever DMT you're already on unless it becomes less effective or stops working. In that case, he or she may want you to try a different one.

DMTs that have been specifically approved by the U.S. Food and Drug Administration (FDA) to treat SPMS include:

  • Mayzent (siponimod): This oral medication treats both RRMS and active SPMS. Initial studies have shown that it helps slow down disease progression at three months and six months with SPMS.
  • Mavenclad (cladribine): Another oral medication, this DMT is generally a second-line treatment if other DMTs aren't effective or you can't take them for some reason.

Symptom Management

Managing your individual symptoms is an important part of your care too, especially as you transition to SPMS. Your doctor may prescribe some different or additional medications to help with MS-related symptoms such as:

A Word From Verywell

While your disease-modifying therapy can help slow the transition from the relapsing phase of MS to the progressive phase, this process will probably still occur. Don't blame yourself if it does—it's a natural process that's unique for every individual and it doesn't happen because of anything you did or didn't do.

Keep being proactive in your care by educating yourself about your disease, looking at treatment options that might work for you, and communicating openly with your doctor about your journey. This can help you live your life to the fullest and empower you to make changes as needed along the way.

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