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Types of Multiple Sclerosis

Four disease courses have been identified in multiple sclerosis: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS).

AJ
Diagnosed in 2000

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How many types of multiple sclerosis are there?

Multiple sclerosis is an unpredictable disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. It can be divided into 4 types, or disease courses, as defined by the International Advisory Committee on Clinical Trials of MS in 1996. They are: 

These are the descriptors currently in use. An international committee organized by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) has proposed a new way of classifying MS. This new method would describe MS as a continuous disease process that is influenced and driven by underlying mechanisms of nervous system damage. This damage is counter-balanced by how well an individual’s body can repair or compensate for that damage.

A change in classification will take years, however. For now, researchers and healthcare providers use the current system.

Review of the types of MS

MS is unpredictable and can vary substantially from person to person. These 4 course descriptors — clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) — might help you know what to expect over the long term. They also help you and your healthcare provider determine what type of disease-modifying therapy might be best for you. Learn more about each of them below.

Clinically Isolated Syndrome (CIS)

Clinically isolated syndrome (CIS) refers to a first episode of neurologic symptoms caused by inflammation and demyelination in the central nervous system. Symptoms of CIS vary from person to person but commonly include:

  • Vision problems (optic neuritis)
  • Vertigo
  • Loss of sensation in the face
  • Weakness in the arms and legs, with one side of the body affected more than the other
  • Difficulty with coordination, balance, walking, speaking and swallowing (ataxia)
  • Bladder problems
To meet the definition of CIS, the episode must last at least 24 hours. Though an episode like this is typical of MS, not all people who have CIS go on to develop MS.

A person with CIS has a high likelihood of a second episode of neurologic symptoms and a diagnosis of relapsing-remitting MS if an MRI (magnetic resonance imaging) shows brain lesions that are similar to those seen in MS. Without those lesions, the likelihood of an MS diagnosis is much lower.

According to the 2017 diagnostic criteria for MS, a person with CIS may be diagnosed with MS if a brain MRI shows:
  • Specific signs of an earlier episode of damage in a different location and
  • Active inflammation in a region other than the one causing the current symptoms

As MRI technology improves, diagnosing MS will be quicker and easier. In the meantime, people with CIS who are considered at high risk for developing MS may be treated with a disease-modifying therapy with approval for that purpose from the U.S. Food and Drug Administration (FDA). Studies show that early treatment of CIS delays the onset of MS.

Read More About CIS

Read More About CIS

Relapsing-remitting MS (RRMS)

Relapsing-remitting MS (RRMS) — the most common disease course — shows clearly defined attacks of new or increasing neurologic symptoms. These attacks are also called relapses or exacerbations. They are followed by periods of partial or complete recovery, or remission. In remissions, all symptoms may disappear or some symptoms may continue and become permanent. However, during those periods, the disease does not seem to progress.

RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity over a specified period of time) or not active, as well as worsening (a confirmed increase in disability following a relapse) or not worsening.

Approximately 85% of people with MS are initially diagnosed with RRMS. (When the disease course progresses, it is considered to be secondary progressive MS.)


This graphic shows the kinds of disease activity that may occur in RRMS over time.
This graphic shows the kinds of disease activity that may occur in RRMS over time. But each person’s experience with RRMS is unique. After a relapse, the new symptoms may disappear without causing a higher level of disability. Or they may partially disappear, resulting in higher disability. As part of a relapse, an MRI often detects new lesions, as shown by the arrows. However, the person may not notice symptoms of the new lesions that indicate MS activity.

Learn More About RRMS

Learn More About RRMS

Secondary progressive MS (SPMS)

Secondary progressive MS (SPMS) follows the initial relapsing-remitting course. Some people diagnosed with RRMS eventually go on to have a secondary progressive course, in which neurologic function worsens progressively or disability accumulates over time.

SPMS can be further characterized as either active (with relapses and/or evidence of new MRI activity during a specified period of time) or not active, as well as with progression (evidence of disability accrual over time, with or without relapses or new MRI activity) or without progression.

This graphic shows the kinds of disease activity that may occur in SPMS over time.
This graphic shows the kinds of disease activity that may occur in SPMS over time. But each person’s experience with SPMS is unique. SPMS follows relapsing-remitting MS. Disability increases over time, with or without signs of disease activity or relapses, or changes on an MRI. In SPMS, the person may have occasional relapses, as well as periods of stability.

Learn More About SPMS

Learn More About SPMS

Primary progressive MS (PPMS)

With PPMS, neurologic function worsens or disability accumulates as soon as symptoms appear, without early relapses or remissions. PPMS can be further characterized as either active (with an occasional relapse and/or evidence of new MRI activity over a specified period of time) or not active, as well as with progression (evidence of disability accrual over time, with or without relapse or new MRI activity) or without progression.

Approximately 15% of people with MS are diagnosed with PPMS.

This graphic shows the kinds of disease activity that may occur in PPMS over time.

This graphic shows the kinds of disease activity that may occur in PPMS over time. But each person’s experience with PPMS is unique. PPMS can have brief periods of stability, with or without a relapse or new MRI activity. It can also have periods of increasing disability, with or without new relapses or lesions on an MRI.

Learn More About PPMS

Learn More About PPMS

Radiologically isolated syndrome (RIS)

Although not considered a course of MS, radiologically isolated syndrome (RIS) has been used to classify those with:

  1. Lesions on the brain or spinal cord — not explained by another diagnosis — consistent with lesions of MS and
  2. No past or current neurological symptoms or abnormalities found on a neurological exam

Often these individuals have had an MRI because of other symptoms, such as headache, and the results showed lesions similar to those seen in MS.

A 2020 study found that little more than half of those with RIS go on to develop MS within 10 years. There are no specific treatment guidelines for RIS. Additional research is needed to further define what factors increase the likelihood that someone with RIS will develop MS. Monitoring of MRI and neurological symptoms, as well as neurological examination, are generally recommended to quickly identify changes. If the diagnosis is MS, you can begin treatment early.

Research interest in RIS is high, and several studies are ongoing that could provide more guidance for monitoring and treatment. In fact, a 2022 study showed that dimethyl fumarate (Tecfidera®, Biogen) extended the time before the development of a first neurological symptom significantly more than a placebo. This adds to the idea that early treatment is protective and supports the idea that MS can begin well before symptoms emerge. Further study is needed, in larger numbers of people with RIS. Additional trials are underway.

Treatments for MS

More than a dozen disease-modifying therapies have been approved by the U.S. Food and Drug Administration (FDA) to treat the different types of MS. The FDA indicates which type of MS each drug can treat. More treatments are available for relapsing forms of MS than for progressive forms. Scientists around the world are actively looking for more effective treatments for progressive forms of MS. Addressing the challenges of progressive MS is a primary target of the Society’s research strategy.

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