Secondary progressive multiple sclerosis (SPMS) is a stage of MS that develops after relapsing-remitting multiple sclerosis, where symptoms gradually worsen over time rather than coming and going in distinct episodes. While there is no cure, treatments and lifestyle adjustments can help manage symptoms and maintain quality of life for as long as possible.

What Is Secondary Progressive Multiple Sclerosis?

Secondary progressive multiple sclerosis is a form of multiple sclerosis that emerges in people who initially had relapsing-remitting MS (RRMS), which is characterized by periods when symptoms flare up followed by periods of recovery. In SPMS, this pattern changes. Instead of experiencing clear cycles of relapses and remissions, people notice their symptoms gradually getting worse over time, even without obvious flare-ups.^[1]

The term “secondary” means this stage develops after, or secondary to, the initial relapsing-remitting phase. During RRMS, the immune system attacks myelin, the protective coating around nerve fibers in the brain and spinal cord. This damage disrupts how nerve signals travel through the body. In SPMS, the frequency and severity of relapses typically decrease or stop altogether, but permanent damage to nerves continues to accumulate.^[3]

The progression from RRMS to SPMS is not the same for everyone. Some people may still experience occasional relapses even after transitioning to SPMS, while others may not have any relapses at all. The rate at which symptoms worsen also varies considerably from person to person. For some, changes happen slowly over many years, while for others the progression can be more rapid.^[12]

There are two main types of SPMS based on whether relapses still occur. Active or relapsing secondary progressive MS (rSPMS) means a person still experiences some flare-ups along with gradual worsening. Inactive or nonrelapsing secondary progressive MS (nrSPMS) means there are no relapses, just a steady decline in function over time.^[1]

Epidemiology

Understanding how common SPMS is and who it affects helps paint a clearer picture of this condition. Most people with multiple sclerosis start with relapsing-remitting MS, which accounts for about 85% of initial MS diagnoses. Of those with RRMS, many will eventually transition to the secondary progressive stage.^[6]

Research shows that approximately 25% of people with RRMS develop SPMS within 10 years of their initial diagnosis, about 50% by 20 years, and more than 75% by 30 years. This transition typically occurs between 10 to 25 years after the first MS diagnosis.^[3][11]

The age at which SPMS develops is fairly consistent across populations. Since RRMS is usually diagnosed before age 40, SPMS generally emerges when people are in their 40s or 50s. The average age at conversion to SPMS is around 40 years old, which is similar to the typical age when people are diagnosed with primary progressive MS, another form of the disease.^[3][5]

Gender patterns in SPMS are notable. Like RRMS, secondary progressive MS is more common in women than men. This differs from primary progressive MS, where roughly equal numbers of men and women are affected. However, being male is actually considered a risk factor for developing SPMS once someone has been diagnosed with RRMS.^[3][1]

Before disease-modifying drugs became available, about half of people with RRMS transitioned to SPMS within 10 years. The introduction of newer treatments has altered the course of MS for many people, potentially delaying or slowing the progression to SPMS, although the exact extent of this delay is still being studied.^[6]

Causes

The exact cause of secondary progressive MS remains unclear to researchers, but what happens inside the body is becoming better understood. SPMS develops in people who already have relapsing-remitting MS, which means the underlying disease process that began with RRMS continues and evolves over time.^[2]

In the early stages of MS, the immune system mistakenly attacks myelin, the protective coating around nerve fibers. This attack is inflammatory in nature, meaning it involves the body’s immune response causing swelling and damage. During RRMS, this inflammation comes in waves, creating the characteristic pattern of relapses followed by periods of recovery.^[1]

Over years of living with RRMS, damage accumulates in the brain and spinal cord. Some of this damage is from previous relapses that didn’t fully heal. When myelin is damaged, nerve signals can’t travel as efficiently. But more importantly, over time the damage extends beyond the myelin to harm the actual nerve fibers, called axons, that lie underneath the protective coating.^[9]

When the disease transitions to SPMS, the nature of the damage changes. The inflammatory attacks that characterized RRMS become less frequent or stop, but nerve damage continues in a different way. Instead of sudden attacks, there is ongoing, gradual deterioration of nerve cells. The nerves keep getting weaker and more damaged little by little, even without the big inflammatory flare-ups that marked the earlier stage of disease.^[1][4]

Why this transition from inflammatory to progressive damage happens is not fully understood. It appears that after years of repeated immune attacks, the nervous system reaches a point where it can no longer repair itself effectively, and nerve cells begin to die. The progression may also involve different disease mechanisms that are less dependent on inflammation and more related to ongoing degeneration of nerve tissue.^[4]

Risk Factors

While not everyone with RRMS will develop SPMS, certain factors increase the likelihood of this transition. The most fundamental risk factor is having relapsing-remitting MS in the first place, as SPMS can only develop in people who have previously had RRMS.^[1]

Gender plays a role in risk. Men with RRMS appear to be more likely to transition to SPMS compared to women, even though RRMS itself is more common in women. This suggests that once MS is established, it may progress differently based on biological sex.^[1]

The age when MS symptoms first appear also matters. People whose MS symptoms start later in life have a higher risk of developing SPMS. This may be because the body’s ability to repair nerve damage decreases with age, making progressive deterioration more likely.^[1]

The pattern of disease activity during the RRMS phase is particularly important. People who experience more frequent and severe relapses early in their disease course are at higher risk of progressing to SPMS. Similarly, those who have significant nerve damage visible on brain and spinal cord scans at the time of their initial diagnosis tend to be at greater risk.^[2][4]

How long someone has lived with MS is another factor. The longer a person has had RRMS, the greater their chance of transitioning to SPMS. This reflects the cumulative nature of nerve damage over time.^[6]

Symptoms

The symptoms of secondary progressive MS gradually become more serious over time, and how quickly they worsen differs from person to person. Sometimes the changes take many years to become noticeable, while other times progression can happen more rapidly. The symptoms are similar to those experienced during RRMS, but instead of coming and going, they persist and intensify.^[1]

Walking difficulties are among the most common symptoms people notice when transitioning to SPMS. This can include trouble with balance and coordination, making it harder to move around safely. Many people find that walking becomes increasingly effortful, and they may tire more easily when trying to cover distances that were previously manageable.^[2]

Overwhelming fatigue is another hallmark symptom that affects most people with SPMS. This isn’t ordinary tiredness that improves with rest. It’s a profound exhaustion that can make even simple daily tasks feel overwhelming. The fatigue may worsen as the day progresses and can significantly impact a person’s ability to work, socialize, and maintain their usual routines.^[4]

Muscle problems are very common in SPMS. People often experience stiffness, called spasticity, which makes muscles feel tight and difficult to move. Muscle spasms can also occur, where muscles contract involuntarily. These muscle issues can interfere with movement and sometimes cause discomfort or pain.^[1]

Changes in sensation are frequent. Many people experience numbness or tingling in their arms or legs. These sensations can range from mild to severe and may affect daily activities like writing, buttoning clothes, or walking safely.^[1]

Cognitive changes often develop as SPMS progresses. People may notice difficulty with thinking clearly, sometimes described as “brain fog.” Memory problems, trouble concentrating, difficulty learning new information, and slower processing of information are all common cognitive symptoms that can impact work, relationships, and daily life.^[4]

Bladder and bowel problems affect many people with SPMS. Bladder issues might include needing to urinate urgently or frequently, or difficulty emptying the bladder completely. Bowel problems can range from constipation to difficulty controlling bowel movements.^[2]

Vision problems may continue or worsen in SPMS. Some people experience double vision, where they see two images instead of one. Others may have blurred vision or difficulty with visual clarity that affects reading, driving, or recognizing faces.^[1]

At first, a person might have only a few of these symptoms affecting one or two areas of daily life. But as SPMS progresses, symptoms typically become more noticeable and may affect multiple aspects of functioning. The accumulation of symptoms over time is what distinguishes SPMS from the relapsing-remitting pattern where symptoms would improve between flare-ups.^[1]

Prevention

While there is no guaranteed way to prevent the transition from RRMS to SPMS, certain approaches may help delay or slow progression. Early and consistent treatment with disease-modifying drugs during the RRMS phase appears to be one of the most important preventive strategies available.^[2]

Disease-modifying therapies work by reducing inflammatory attacks on the nervous system during RRMS. By minimizing the frequency and severity of relapses, these medications help limit the accumulation of permanent nerve damage. Some evidence suggests that effective use of these medications during RRMS may slow the transition to SPMS or reduce its severity when it does occur.^[4]

Maintaining overall health through lifestyle choices is another important aspect of prevention. A nutritious diet, particularly one that reduces inflammation, may be beneficial. The Mediterranean diet, which is high in fish, vegetables, and nuts and low in red meat, has been shown to have protective effects on the brain and nervous system.^[10]

Regular physical activity is strongly recommended for people with MS. Exercise helps maintain strength, flexibility, and cardiovascular health. It can also reduce fatigue, improve mood, and may have protective effects on the brain and spinal cord. Even light to moderate exercise is beneficial and should be continued throughout the disease course.^[10]

Maintaining a healthy weight is important. Research shows that people who are overweight tend to have more active MS and a faster progression from RRMS to SPMS. Weight management through diet and appropriate exercise can be a valuable part of disease management.^[10]

Getting adequate vitamin D may play a role in slowing MS progression. Studies suggest that sufficient vitamin D levels might lower MS risk, improve quality of life, and potentially delay the transition from RRMS to SPMS. Vitamin D can be obtained through sun exposure, certain foods, or supplements as recommended by a healthcare provider.^[19]

Avoiding tobacco smoke is crucial for people with MS. Smoking has been linked to more active disease and faster progression. If someone with MS smokes, quitting should be a priority, and healthcare providers can offer resources and support to help with cessation.^[14]

Regular medical monitoring is essential. Consistent follow-up with healthcare providers, including periodic MRI scans and neurological assessments, helps track disease activity and allows for timely adjustments to treatment plans when needed.^[4]

Pathophysiology

The pathophysiology of secondary progressive MS involves complex changes in how the nervous system functions and responds to damage. Understanding these changes helps explain why symptoms develop and progress the way they do.

Multiple sclerosis affects the central nervous system, which includes the brain, spinal cord, and optic nerves. These structures rely on nerve cells, or neurons, to transmit electrical signals that control virtually every function in the body, from movement to thinking to sensation. Each neuron has a long fiber called an axon that carries these signals, and axons are wrapped in myelin, a fatty substance that acts like insulation on electrical wires.^[2]

In RRMS, the immune system produces inflammatory attacks against myelin. During these attacks, immune cells infiltrate the brain and spinal cord and damage the myelin sheath. When myelin is destroyed, it’s called demyelination. Areas where myelin has been stripped away are called lesions or scars. These damaged areas can sometimes be seen on MRI scans as bright spots.^[7]

When myelin is damaged, nerve signals slow down or get blocked entirely, like when insulation is stripped from an electrical wire. This disruption causes the various symptoms of MS—if the lesion is in an area controlling movement, weakness or coordination problems result; if it’s in an area processing vision, visual symptoms occur.^[2]

The body has some ability to repair damaged myelin, a process called remyelination. During remission periods in RRMS, some repair occurs, and symptoms can improve or resolve. However, this repair is never perfect. With repeated attacks over years, the capacity for repair diminishes, and damage accumulates.^[7]

As MS progresses to the secondary progressive stage, the pathophysiology shifts. The inflammatory component becomes less prominent—there are fewer immune cells actively attacking myelin—but damage continues through different mechanisms. The axons themselves, the nerve fibers that were protected by myelin, begin to deteriorate and die. This process is called neurodegeneration.^[4]

Why axons degenerate in progressive MS is not completely understood, but several factors appear to play a role. Years of demyelination leave axons vulnerable because they no longer have their protective coating. Without myelin, axons must work harder to transmit signals, which stresses them. Over time, this stress, combined with ongoing inflammation at a lower level and aging processes, leads to axonal death.^[11]

When nerve cells die, they cannot be replaced. Unlike myelin damage, which can sometimes be partially repaired, the loss of axons is permanent. As more and more nerve cells die, there are fewer pathways available to transmit signals throughout the nervous system. This progressive loss of functioning nerve tissue is what drives the gradual accumulation of disability in SPMS.^[7]

Brain atrophy, or shrinkage, is another important aspect of SPMS pathophysiology. As nerve cells die off faster than normal aging would cause, the brain and spinal cord actually become smaller. This loss of nerve tissue correlates with worsening disability over time. People with more severe atrophy typically experience greater functional impairment.^[5]

During SPMS, some low-level inflammation may continue within the central nervous system, even though the large inflammatory attacks characteristic of RRMS become less frequent. This persistent inflammation, combined with the ongoing neurodegeneration and loss of the nervous system’s ability to compensate for damage, creates the progressive worsening that defines this stage of the disease.^[11]