An Overview of Secondary Progressive Multiple Sclerosis (SPMS)

When you stop having relapses but your MS worsens

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Maybe you've just been diagnosed with secondary progressive MS (SPMS). Or maybe you're one of the 85% to 90% of people with multiple sclerosis (MS) who are initially diagnosed with relapsing-remitting MS (RRMS) and you're not sure how your healthcare provider 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.

Signs and Symptoms of Secondary Progressive Multiple Sclerosis
Verywell / JR Bee


The majority of people with RRMS transition to SPMS, which is characterized by steadier progression of symptoms and disability with fewer or no relapses (when symptoms get worse). Remissions after a relapse aren't complete and symptoms continue.

However, since the development of disease-modifying therapies, the progression to secondary MS has become less frequently noted.

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.

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 healthcare provider 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.

Some people may worry that they're entering the progressive phase of MS because they stop having relapses. However, if your neurological exam is stable, this is a very good sign, as it means 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 to Solu-Medrol during these relapses.

There's a Large Amount of Damage Seen on MRI

When you have an MRI, you and your healthcare provider 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)
  • Confluent lesions, meaning small lesions forming larger ones
  • 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 correlate with 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.

Your healthcare provider 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 healthcare provider 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 practitioner 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 healthcare provider 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 of worsening disability.

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.


Symptomatic Treatment of 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

Most disease-modifying agents have not shown benefit in patients with SPMS. However, recently three drugs were approved by the FDA to be used in patients with SPMS who are still having active disease.

  • 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.
  • Zeposia (ozanimod): This is a more recent drug development. It is an oral medication that treats relapses in MS. It is thought that Zeposia works by stoping immune cells from moving out of the lymph nodes.

Other types of drugs that may be used include monoclonal antibodies, such as Rituxan (rituximab) and Tysabri (natalizumab), a type II topoisomerase inhibitors, such as mitoxantrone, glutocorticoids, and cytoxan.

In rare cases, a stem cell transplant may be an option.

Symptom Management

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

A Word From Verywell

Even though the treatment for SPMS is currently suboptimal, feel reassured that there are many ongoing research studies trying to come up with treatments that will hopefully stop the progression of this disease as well as improve disability.

Until then, 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 healthcare provider about your journey. This can help you live your life to the fullest and empower you to make changes as needed along the way. Our Doctor Discussion Guide below can help you start that conversation.

Multiple Sclerosis Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

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3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Multiple Sclerosis Society. Diagnosing SPMS.

  2. Olek MJ, Howard J. Clinical Presentation, Course, and Prognosis of Multiple Sclerosis in Adults. UpToDate.

  3. Olek MJ, Mowry E. Treatment of Progressive Multiple Sclerosis in Adults. UpToDate.

Additional Reading

By Julie Stachowiak, PhD
Julie Stachowiak, PhD, is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award, Health Category.