Secondary progressive multiple sclerosis (SPMS) is a stage of MS that follows relapsing-remitting multiple sclerosis (RRMS).

With this type of MS, a person’s disability gets steadily worse. The individual is no longer likely to have relapses, when the symptoms get worse but then get better.

Most people with RRMS will eventually develop SPMS. However, because of advancements in disease-modifying treatments, fewer people today develop SPMS than before, and the transition to SPMS occurs later.

SPMS can be further classified as:

  • active (with relapses or evidence of new brain lesions) or not active
  • with progression (which means that the disease worsens over time) or without progression

Active and inactive forms can both occur with or without progression.

Causes of SPMS

It is not well-understood what factors influence the progression from RRMS to SPMS, and progression is difficult to predict.

The median time from RRMS onset to SPMS is about 19 years. The older the patient at the onset, the shorter the time from onset to secondary progression.

Incomplete recovery from an initial exacerbation also is associated with a shorter time to secondary progression. In some studies, male sex was associated with a shorter time to secondary progression than female sex, but data are inconsistent.

Several studies reported that visual or sensory, and sometimes brainstem-related symptoms are associated with an increased time to secondary progression. In contrast, spinal cord-related symptoms are associated with shorter time to secondary progression.

In some studies, the number of relapses during the first two-to-five years of the disease was inversely related to the time to secondary progression, but the data are inconsistent.

The role of inflammation in SPMS also remains unclear. It seems to be smaller in SPMS than in relapsing forms of MS, and disease progression appears to be due to increased nerve damage.

Symptoms of SPMS

While patients in relapsing disease stages experience relapses and remissions of symptoms, remissions in patients with SPMS are less pronounced with only a mild reduction of symptoms. Instead, symptoms gradually worsen over time.

There is a wide range of SPMS symptoms, and they differ in severity from patient to patient.

Common symptoms of SPMS include:

  • numbness or tingling
  • chronic fatigue
  • cognitive problems
  • depression
  • coordination problems
  • sexual difficulties
  • bladder and bowel dysfunction
  • weak and stiff legs
  • vision problems

Patients with SPMS also may experience less common symptoms. These symptoms are often paroxysmal, which means that they are felt suddenly and disappear quickly.

Such symptoms include the following:

  • trigeminal neuralgia, a condition that affects the trigeminal nerve, characterized by a sudden burning sensation in the face
  • pseudobulbar affect, which is caused by lesions in the amygdala, a brain region that controls emotions, and is characterized by unprovoked crying or laughing
  • the feeling of electric shocks along the spine, which are caused by inappropriate communication between damaged nerves in the neck and the brain
  • unusual sensory symptoms, such as a strange sensation of cold or wetness along the limbs
  • dysesthesia, which is an abnormal and unpleasant sense of touch, such as the feeling of a tight hug and itchiness
  • blurred vision
  • optical illusions
  • seizure-like spasms in the arms and legs
  • dizziness, vertigo, and migraines

How SPMS differs from other disease courses

In RRMS, symptoms are caused by inflammation, and come and go in waves. In between flareups, patients experience much milder symptoms or may even be symptom-free. Relapses refer to a temporary worsening of symptoms. These come and go, but their severity is stable, which means that they do not worsen over time.

In contrast, SPMS is driven by neurodegeneration, which means that nerve damage worsens over time. At the SPMS stage, patients experience progression or a continuous worsening of symptoms. Symptom flareups can still occur, but symptom changes are much less drastic than in the RRMS stage. In SPMS, symptoms do not disappear even in the remission phases.

Diagnosis of SPMS

Establishing a diagnosis of SPMS can be challenging, as the changes between RRMS and SPMS occur gradually. The date of disease progression is difficult to define and is usually determined retrospectively once a constant rate of change from a remitting to a progressive course is observed. Typically, at least six months of progression must be noted before RRMS is considered as SPMS.

SPMS is characterized by a reduction in the number and severity of relapses, while at the same time the damage progresses. The diagnosis of SPMS, therefore, involves a careful analysis of the symptoms. Disease progression can be measured with the expanded disability status scale (EDSS). The scale ranges from 0 to 10, with 0.5-unit increments. The higher the number on the scale, the more severe the symptoms.

EDSS assesses:

  • muscle weakness or difficulty moving limbs
  • difficulties with speech and swallowing
  • numbness or reduced sensation
  • impaired visual function
  • loss of balance and coordination
  • ataxia (lack of muscle control) and tremor
  • bowel and bladder problems
  • cognitive impairment

A neurologic examination and magnetic resonance imaging (MRI) also may detect disease progression.

Treatment of SPMS

Treatment of MS is always a balance between effectiveness and side effects, and it can take time to find a satisfying solution. Once current medications no longer sufficiently control the symptoms, different therapies may be tried.

There are a several disease-modifying medications for the treatment of SPMS:

IFN beta

Interferons are proteins that control inflammation. Interferon (INF) beta has been shown to reduce inflammation in MS. Different INF beta medications exist for the treatment of MS, but their use for SPMS is controversial.

Immune suppressive medications

Novantrone inhibits the proliferation of specific immune cells. It is a U.S. Food and Drug Administration (FDA)-approved medication for the treatment of SPMS, progressive-relapsing MS (PRMS), and worsening RRMS.

Cyclophosphamide works by inhibiting the division of immune cells. The medication can slow progression in SPMS patients who show an inadequate response to other disease-modifying treatments.

Monoclonal antibodies

Tysabri is an antibody that blocks the entry of immune cells to the brain. It is an FDA-approved medication for relapsing forms of MS. Clinical data suggest that the medication might reduce the progression of upper limb disability in SPMS patients.

Stem cell therapies

Mesenchymal stem cells (MSCs) are adult stem cells found in different parts of the body, such as adipose (fat) tissue, bone marrow, and skin. MSCs can potentially develop into myelin-producing cells and reverse the damage to the myelin sheath — the protecting coat surrounding nerve fibers — that is characteristic of MS.

MSCs therapy for multiple sclerosis is currently being investigated in clinical trials. Some data suggest they could be of clinical benefit for SPMS patients.

Autologous hematopoietic stem cells (aHSCTs) are extracted from a person’s blood or bone marrow. After ablation of the patient’s immune system, a process called immunoablation, the aHSCTs are used to reconstitute the individual’s immune system. The procedure is supposed to halt the body’s autoimmune attack on myelin.

aHSCTs are currently under investigation in clinical trials, and a meta-analysis suggests that it may slow the progression of SPMS.

Other therapies

Siponimod decreases the number of lymphocytes in the blood, thereby reducing the inflammation that is involved in MS. The medication has been found to reduce the risk of progression in SPMS patients. It was approved by the FDA in March 2019 for the treatment of active SPMS and relapsing forms of MS.

Another therapy, Simvastatin, is a cholesterol-lowering medication that also has anti-inflammatory and potentially neuroprotective properties. Data from clinical trials suggest that the medication can lower the rate of brain atrophy.

Vumerity regulates the immune response and lowers oxidative stress, and is thereby supposed to prevent the degeneration of myelin. The medication is approved by the FDA for the treatment of SPMS and relapsing forms of MS.

A tyrosine kinase inhibitor, Masitinib targets immune cells called mast cells and macrophages. It thereby reduces inflammation and neuronal damage. Data from a pilot study suggest that the medication may be of benefit for people with relapse-free SPMS.


Apart from disease-modifying therapies, medications that help control symptoms are used for the management of SPMS and other forms of MS. Certain medications also can be used to decrease the side effects of disease-modifying therapies.

These include medications to:

  • reduce muscle spasms and tremors
  • improve gait
  • relieve fatigue
  • reduce dizziness
  • improve bowel function
  • treat sexual problems
  • reduce bladder issues
  • treat depression and emotional changes
  • manage pain

A healthy diet also can improve the overall health and general well-being of MS patients. Several different diets have been suggested to be beneficial for people with MS, but there is no robust scientific evidence that supports one particular diet. Most recommended diets have in common that they restrict highly processed foods, and foods with a high glycemic index, and focus instead on an increased intake of fruits and vegetables. A glycemic index is a relative ranking of carbohydrate in foods according to how they affect blood glucose levels.

Exercise can help improve heart, bladder, and bowel function, increase strength, and reduce fatigue and depression. Exercise programs should always be individualized and adapted to the patient’s capabilities and limitations. Yoga, tai chi, and water exercises are examples of physical activities that may benefit MS patients.


Last updated: Nov. 12. 2019


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