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Clinically Isolated Syndrome (CIS)


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Clinically isolated syndrome (CIS) is one of the MS disease courses. CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS). CIS can be either monofocal or multifocal:

  • Monofocal episode: The person experiences a single neurologic sign or symptom — for example, an attack of optic neuritis — that is caused by a single lesion.
  • Multifocal episode: The person experiences more than one sign or symptom — for example, an attack of optic neuritis accompanied by numbness or tingling in the legs — caused by lesions in more than one place.

The episode usually has no associated fever or infection and is followed by a complete or partial recovery. 

CIS progression to MS

Individuals who experience CIS may or may not go on to develop MS. In diagnosing CIS, the healthcare provider faces two challenges: first, to determine whether the person is experiencing a neurologic episode caused by damage in the CNS; and second, to determine the likelihood that a person experiencing this type of demyelinating event is going to go on to develop MS.

  • High risk of developing MS: When CIS is accompanied by magnetic resonance imaging (MRI)-detected brain lesions that are similar to those seen in MS, the person has a 60 to 80 percent chance of a second neurologic event and diagnosis of MS within several years.
  • Low risk of developing MS: When CIS is not accompanied by MRI-detected brain lesions, the person has about a 20 percent chance of developing MS over the same period of time.

According to the 2017 revisions to the diagnostic criteria for MS, the diagnosis of MS can be made when CIS is accompanied by MRI findings (old lesions or scars) that confirm that an earlier episode of damage occurred in a different location in the CNS. The new criteria also allows for the presence of oligoclonal bands in a person's cerebrospinal fluid to help make the diagnosis. As MRI technology becomes more advanced, it is likely that the diagnosis of MS will be made more quickly and there will be fewer people diagnosed with CIS.

An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment with a disease-modifying therapy in order to delay or prevent a second neurologic episode and, therefore, the onset of MS. In addition, early treatment may minimize future disability caused by further inflammation and damage to nerve cells, which are sometimes silent (occurring without any noticeable symptoms). Several medications have a Food and Drug Administration (FDA) indication for CIS: Avonex®, Betaseron®, Extavia® and Mayzent®.

Who gets CIS, and when?

Like MS, CIS is not directly inherited, and it is not contagious. CIS is two to three times more common in women than men. Seventy percent of people diagnosed with CIS are between the ages of 20 and 40 years (average 30 years) but people can develop CIS at older or younger ages.

How is CIS different from MS?

Based upon clinical symptoms alone, CIS and MS may appear the same. In both, damage to the myelin sheath (demyelination) interferes with the way nerve impulses are carried from the brain, resulting in neurologic symptoms.

  • A person with CIS, by definition, is experiencing the first episode of symptoms caused by inflammation and demyelination in the CNS; a person with MS has experienced more than one episode.
  • With CIS, an MRI may demonstrate damage only in the area responsible for the current symptoms; with MS, there may be multiple lesions on MRI in different areas of the brain.
  • According to the 2017 revisions to the diagnostic criteria, when CIS is accompanied by evidence on MRI that another episode has occurred, the diagnosis of MS can be made. The presence of oligoclonal bands in a person's cerebrospinal fluid can also help make the diagnosis.


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