Multiple Sclerosis (MS)

Secondary progressive multiple sclerosis (SPMS) is a form of multiple sclerosis that develops from relapsing-remitting multiple sclerosis (RRMS).1 Secondary progressive MS is characterized by progressive worsening of neurologic function over time.

SPMS can be active — ie, with relapses and/or evidence of new magnetic resonance imaging (MRI) activity — or not active. It can also be with or without progression. In SPMS with progression, there is evidence of increased disability. This may or may not be accompanied by relapses or new MRI activity.1 

SPMS is twice as common in women as in men. It is also more common in people of Caucasian descent.2

Secondary Progressive MS Causes

Multiple sclerosis is characterized by an immune attack on the oligodendrocytes, which make up the myelin sheath, leading to inflammation and neuronal damage. The exact cause of multiple sclerosis is not known, however, genetic predispositions combined with environmental factors play an important role in the pathogenesis of this disease.3 

Not all patients with RRMS progress to SPMS, and the disease course varies from patient to patient. However, approximately 65% of patients with RRMS do subsequently develop SPMS.4

During the early stages of RRMS, the axonal loss does not have a substantial clinical impact. However, as the disease progresses, additional lesions form, which means that RRMS can progress to SPMS because the brain exhausts its capacity to compensate for the further axonal loss.5

Frequent severe relapses and large numbers of brain and spinal cord lesions at the time of diagnosis may increase the risk of progression.2

Secondary Progressive MS Symptoms

The symptoms of SPMS include fatigue, numbness or tingling, spasticity, muscle stiffness, mobility and coordination issues, vision impairment, urinary urgency, and cognitive problems.2

Although patients with SPMS may experience periods of remission, these are usually not complete and some symptoms remain during the periods of remission. The main feature of SPMS, as with primary progressive MS, is the gradual worsening of disability.

Secondary Progressive MS Diagnosis

A patient may be diagnosed with SPMS only if they have previously been diagnosed with RRMS. Although it is not possible to tell exactly when the transition is occurring, it is generally characterized by a reduction in inflammatory relapses. However, existing symptoms tend to worsen over time.6

Strategies that can be used to make a diagnosis of SPMS include taking a careful medical history of the change in the patient’s symptoms and repeated neurological examinations and MRI scans.

To develop an objective measure that reflects long-term disease worsening and better diagnoses SPMS, researchers used MSBase datasets containing clinical data from 34,154 patients in 113 MS centers in 34 countries to develop a definition of SPMS.7 According to this finding, SPMS is defined as a 1-point worsening in the expanded disability status scale (EDSS) in patients with an EDSS of 5.5 or less or a worsening of 0.5 points in EDSS in those with an EDSS of 6 or more without a relapse. Other criteria include an EDSS of at least 4, a pyramidal functional system (FS) score of 2 or more, a confirmed worsening over 3 months or more, and confirmation of worsening within the same FS as worsening onset.8

Secondary Progressive MS Treatment

There are many disease-modifying treatments approved by the US Food and Drug Administration for multiple sclerosis.9 These include interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), glatiramer acetate (Copaxone®, Glatopa®), ofatumumab (Kesimpta®), teriflunomide (Aubagio®), monomethyl, dimethyl, and diroximel fumarate (Bafiertam™, Tecfidera®, and Vumerity®), fingolimod (Gilenya®), cladribine (Mavenclad®), siponimod (Mayzent®), ponesimod (Ponvory™), ozanimod (Zeposia®), alemtuzumab (Lemtrada®), mitoxantrone (Novantrone®), ocrelizumab (Ocrevus®), and natalizumab (Tysabri®).

The disease-modifying treatments can have different levels of effectiveness and various side effects including injection site irritation, flu-like symptoms, gastrointestinal symptoms, changes in liver function, and increased risk of infections.10  

Before a patient is diagnosed with SPMS, they must first be diagnosed with RRMS, which means they will have already started on one of the disease-modifying treatments. Unless they are no longer controlling their disease, patients may stay on their medication in the secondary progressive phase of their disease based on individual preference and shared decision-making.11 However, in the UK it is recommended that disease-modifying treatments are stopped once a diagnosis of nonrelapsing SPMS is confirmed.12

Other treatment options for SPMS include symptomatic management of the disease and rehabilitation including physiotherapy, occupational therapy, and speech therapy.11 Healthy living habits such as healthy eating, physical activity, smoking cessation, and reduced alcohol consumption may also ensure patients have a higher quality of life.13


  1. Secondary progressive MS (SPMS). National Multiple Sclerosis Society. Accessed June 11, 2021.
  2. Secondary-progressive multiple sclerosis. Cedars Sinai. Accessed June 11, 2021.
  3. Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol. 2019;6(9):1905-1922. doi:10.1002/acn3.50862
  4. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19(1):1-10. doi:10.22074/cellj.2016.4867
  5. Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol. 2014;27(3):271-278. doi:10.1097/WCO.0000000000000094
  6. Diagnosing SPMS. National Multiple Sclerosis Society. Accessed June 11, 2021.
  7. MSBase Neuro-Immunology Registry. MSBase. Accessed June 11, 2021.
  8. Lorscheider J, Buzzard K, Jokubaitis V, et al. Defining secondary progressive multiple sclerosis. Brain. 2016;139(Pt 9):2395-2405. doi:10.1093/brain/aww173
  9. Disease-modifying therapies for MS. National Multiple Sclerosis Society. Updated April 2021. Accessed June 11, 2021.
  10. Choices – disease modifying therapies. MS-UK. Accessed June 11, 2021.
  11. Treating SPMS. National Multiple Sclerosis Society. Accessed June 11, 2021.
  12. Scolding N, Barnes D, Cader S, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015;15(4):273-279. doi:10.1136/practneurol-2015-001139
  13. Diet, exercise & healthy behaviors. National Multiple Sclerosis Society. Accessed June 11, 2021.

Reviewed by Kyle Habet, MD on 7/1/2021

Reviewed by Kyle Habet, MD, on 7/1/2021.