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4 Types of Multiple Sclerosis: Differences and Common Symptoms

Multiple Sclerosis (MS) is a chronic degenerative disease affecting nearly 1 million people in the U.S. It occurs when the immune system attacks and damages the central nervous system, leaving behind scar tissue in the form of lesions. This is where MS gets its name: “sclerosis” means “scarring.” Depending on where lesions occur—the spinal cord, the brain, or even the optic nerves—symptoms of the disease can vary greatly. The body can sometimes repair itself to an extent after an attack, but nerve damage may also progress until symptoms become long-lasting.

As with other degenerative conditions, it’s impossible to predict how MS will develop on a case-by-case basis, but there are four courses, or phenotypes, that the progression is expected to take. These four disease were defined in 2013 by the International Advisory Committee on Clinical Trials for MS:

  • Clinically Isolated Syndrome (CIS)
  • Relapsing-Remitting (RRMS)
  • Secondary Progressive (SPMS)
  • Primary Progressive (PPMS)

By describing the most common patterns of progression that have been observed in MS patients, phenotypes can be used for a clinical diagnosis. The progression of MS takes years to develop, and being aware of what phenotypes exist improves the chances of receiving a diagnosis early on.

Read on to learn about the four phenotypes of MS, how you can identify common symptoms in a loved one early on, and how these might progress over time.

Common Symptoms of MS

Phenotypes of MS describe four distinct diagnoses, but there are many common symptoms of MS that occur with any of them. Some of the most prevalent include:

  • Fatigue
  • Numbness or tingling
  • Walking difficulties
  • Muscle weakness
  • Dizziness
  • Bladder dysfunction
  • Vision problems
  • Pain and itching
  • Cognitive changes

Any of these symptoms should be discussed with a healthcare provider as soon as possible. Because the progression of multiple sclerosis is so complex, it’s important to obtain an initial diagnosis of one of the four MS phenotypes to access the most effective care.

Sometimes initial symptoms aren’t present for a doctor to provide a diagnosis, but lesions are discovered by chance on an MRI scan that a patient undergoes for another reason. These cases where lesions are present without symptoms aren’t considered a phenotype of MS, but they are classified as radiologically isolated syndrome (RIS).

A 2020 study found that about 51% of people diagnosed with RIS go on to develop MS, but there are no official treatment guidelines for the condition. Further study is needed to determine why some people with RIS progress to MS and not others.

Clinically Isolated Syndrome (CIS)

Clinically Isolated Syndrome (CIS) is an episode of MS symptoms that occurs before the full onset of the disease, lasting for at least 24 hours. This is an isolated incident that occurs before any other MS symptoms, and will often prompt a visit to a doctor who may order an MRI scan.

Some people who experience CIS never go on to develop MS. But if lesions are visible on an MRI, then the risk of MS onset is high. Knowing this much is extremely important, because early treatment with disease-modifying therapies has been shown to delay the onset of MS for people with CIS and lesions.

Relapsing-Remitting MS (RRMS)

Relapsing-Remitting MS is the most common phenotype and the initial diagnosis for about 85% of MS patients. It’s characterized by periods of attack (relapse) and recovery (remission). During a relapse, neurological symptoms appear and persist until the recovery period, when symptoms fully or partially abate. RRMS cycles are unique to each patient and need to be evaluated to assess whether or not a treatment plan is working. In a clinical setting, cycles can be described as active or not active, referring to the frequency at which they occur, with symptoms worsening or not worsening with each relapse. These modifiers are used to determine if a treatment plan is working or whether a switch should be made.

Many people with RRMS recover fully or substantially after each attack, though each case presents its own unique challenges. Ideally, an early diagnosis means a quicker route to the best method of treatment to live a full and active life.

Secondary Progressive MS (SPMS)

The Secondary Progressive form of the MS is characterized by similar cycles of relapse and remission, but a person’s level disability can also steadily increase without an attack taking place.

Modifiers used to describe SPMS are active, not active, with progression, and without progression. A case is considered active with MRI activity or relapses and progressing when level of disability is worsening. As with RRMS, people with SPMS may experience any combination of these modifiers, from not active with progression to active without progression. Many, however, see a prolonged progression of symptoms without remission.

Before disease-modifying therapies were available, nearly half of all RRMS patients experienced a progression of symptoms developing into SPMS within ten years. Experts agree that these newer therapies make an impact, but not enough research has been done to determine the extent of their effect on the progression of MS.

Primary Progressive MS (PPMS)

This is the rarest of the four major courses of MS, seen in 10-15% of patients. In clinical diagnosis, the same modifiers are used as for SPMS (active, not active, with progression, and without progression).

From the first onset of MS symptoms, people with PPMS will generally experience a worsening level of disability over time without any cycles of relapse and remission early on. PPMS tends to be more difficult to treat, and more often results in a level of disability that requires greater assistance to complete daily activities.

Multiple sclerosis can be challenging to recognize and diagnose as symptoms vary widely between individuals. In each case, the best outcomes often result from close monitoring of symptoms and different treatment methods over time.

The cause of MS is unknown, and a number of factors make the disease especially difficult to research. The definition of four phenotypes is an advancement that allows for clinicians to identify more accurate trends and effective treatments between groups. The more knowledgeable we are about the symptoms and potential courses of MS, the better prepared we will be to care for disabled loved ones.

Are you caring for a loved one with MS at home? Careforth could help. Learn more about our coaching and support program for caregivers of Medicaid-eligible friends and family members.


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