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Clinically Isolated Syndrome (CIS)


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Clinically isolated syndrome (CIS) is a term that describes a first and single neurologic episode of inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS) lasting at least 24 hours. It is thought that the immune system mistakenly targets the myelin covering the nerve cells in the brain; symptoms occur because the demyelination disrupts the normal transmission of nerve impulses.

The episode can involve one area (monofocal) or several areas (multifocal) of the CNS and may or may not be an early sign of multiple sclerosis (MS). In a monofocal episode, the person experiences a single neurologic sign or symptom (e.g. optic neuritis); in a multifocal episode, more than one sign or symptom (e.g., optic neuritis accompanied by leg weakness or numbness and tingling) is experienced.

The episode usually has no associated fever or infection and is followed by at least a partial resolution of symptoms. A person experiencing a second clinical attack will be considered to have progressed to MS. In addition, based upon the 2010 revisions to the McDonald diagnostic criteria, a person with CIS and specific findings on MRI can be diagnosed with MS. 

CIS progression to MS

Studies vary widely in their report of the proportion of patients with CIS who develop MS. A brain scan (MRI) can help to more precisely estimate the risk. The long-term risk of developing MS is 60 to 80 percent when lesions consistent with MS are seen on MRI, and about 20 percent when the brain scan is normal.

Accurate diagnosis permits early initiation of treatment – which studies have shown can delay conversion of CIS to CDMS. In addition, early treatment may minimize future disability caused by further inflammation and damage to nerve cells, which are sometimes silent (occurring even if no symptoms can be observed).

Who gets CIS, and when?

Like MS, 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 patients can present at older or younger ages.

How is CIS different from MS?

Based upon clinical symptoms alone, CIS and MS 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, experiences only one attack; a person with MS has more than one attack.
  • With CIS, an MRI may demonstrate damage only in the area responsible for the current symptoms; with MS, there may be multiple brain lesions demonstrated on MRI.