Source: US National Multiple Sclerosis Society

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

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 Central Nervous System (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 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.
  • Lower risk of development MS: When CIS is not accompanied by MRI-detected lesions, the person has about a 20 percent chance of developing MS over the same period of time.
  • According to the 2010 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. 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 medication 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 even if no symptoms can be observed).

Several medications are now approved by the U.S. Food and Drug Administration (FDA) for CIS: Avonex®, Betaseron®, Copaxone®, Extavia®.

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 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 brain lesions demonstrated on MRI.
According to the 2010 revisions to the diagnostic criteria for MS, when CIS is accompanied by specific findings on MRI that demonstrate that another episode has occurred in the past, the diagnosis of MS can be made.

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