What is clinically isolated syndrome (CIS)?

Clinically isolated syndrome (CIS) is an episode of neurologic symptoms. CIS involves demyelination in your central nervous system. That means you’ve lost some myelin, the coating that protects nerve cells.

To be classified as CIS, the episode must last at least 24 hours. It can’t be associated with fever, infection, or other illness.

CIS, by its very name, indicates that you’ve had an isolated incident. It doesn’t mean you should expect more or that you’ll definitely develop multiple sclerosis (MS). However, CIS is sometimes the first clinical episode of MS.

Continue reading to learn more about the connection between CIS and MS, how the distinction is made, and what your next steps should be.

The big difference is that CIS is a single episode while MS involves multiple episodes, or flare-ups.

With CIS, you don’t know if it’ll ever happen again. Conversely, MS is a lifelong disease without a cure, though it can be managed.

Some symptoms of CIS are:

  • Optic neuritis. This is a condition in which your optic nerve is damaged. This can cause poor vision, blind spots, and double vision. You might also experience eye pain.
  • Transverse myelitis. This condition involves damage to your spinal cord. Symptoms can include muscle weakness, numbness and tingling, or bladder and bowel issues.
  • Lhermitte’s sign. Also known as barber chair phenomenon, this condition is caused by a lesion on the upper part of your spinal cord. An electric shock-like feeling goes from the back of your neck to your spinal column. This may happen when you bend your neck downward.

CIS can cause difficulties with:

  • balance and coordination
  • dizziness and shakiness
  • muscle stiffness or spasticity
  • sexual function
  • walking

Both CIS and MS involve damage to the myelin sheath. Inflammation causes the formation of lesions. These interrupt signals between your brain and the rest of the body.

Symptoms depend on the location of the lesions. They can range from barely detectable to disabling. It’s hard to distinguish CIS from MS based on symptoms alone.

The difference between the two conditions may be detectable through an MRI. If there’s evidence of only one episode, you probably have CIS. If images show multiple lesions and evidence of other episodes separated by space and time, you may have MS.

CIS is the result of inflammation and damage to myelin. This can occur anywhere in the central nervous system. It’s not exactly clear why this happens. Some risk factors have been identified:

  • Age. Although you can develop CIS at any age, it tends to be diagnosed in young adults between the ages of 20 and 40.
  • Genetics and environment. Your risk of developing MS is higher if you have a parent who has it. In general, MS is also more common in areas further from the equator. It’s possible that it’s a combination of an environmental trigger and a genetic predisposition.
  • Gender. CIS is two to three times more common in women than men.

A CIS episode in your past puts you at increased risk for developing MS.

Your primary care physician will probably refer you to a neurologist. Your complete medical history and discussion of your symptoms is the first step. Then, you’ll need a neurological exam, which could include checking your:

  • balance and coordination
  • eye movements and basic vision
  • reflexes

Some diagnostic tests to help find the cause of your symptoms are:

Blood tests

There’s no blood test that can confirm or rule out CIS or MS. But blood tests play an important role in ruling out other conditions that present with similar symptoms.


An MRI of your brain, neck, and spine is an effective way to detect lesions caused by demyelination. Dye injected into a vein can highlight areas of active inflammation. The contrast dye helps determine if this is your first episode or if you’ve had others.

When you have one symptom caused by one lesion, it’s called a monofocal episode. If you have several symptoms caused by multiple lesions, you’ve had a multifocal episode.

Lumbar puncture (spinal tap)

After a spinal tap, your cerebrospinal fluid is analyzed to look for protein markers. If you have more than the normal amount, it may suggest increased risk of MS.

Evoked potentials

Evoked potentials measure how your brain responds to sight, sound, or touch. About 30 percent of people with CIS have abnormal results to visual-evoked potentials.

Before a diagnosis can be made, all other possible diagnoses must be excluded.

Some of these are:

  • autoimmune disorders
  • genetic diseases
  • infections
  • inflammatory disorders
  • metabolic disorders
  • neoplasms
  • vascular disease

CIS doesn’t necessarily progress to MS. It may forever remain an isolated event.

If your MRI detected MS-like lesions, there’s a 60 to 80 percent chance that you’ll have another flare-up and an MS diagnosis within a few years.

If the MRI didn’t find MS-like lesions, the chance of developing MS within a few years is about 20 percent.

Repeat flare-ups of disease activity is characteristic of MS.

If you have a second episode, your doctor will likely want another MRI. Evidence of multiple lesions separated by time and space points toward a diagnosis of MS.

A mild case of CIS may clear up on its own within a few weeks. It may resolve before you ever get to a diagnosis.

For serious symptoms such as optic neuritis, your doctor might prescribe high-dose steroid treatment. These steroids are given by infusion, but in some cases can be taken orally. Steroids can help you recover from symptoms faster, but they don’t affect your overall outlook.

There are a number of disease-modifying drugs used to treat MS. They’re designed to reduce the frequency and severity of flare-ups. In people with CIS, these medications can be used in the hope of delaying onset of MS.

Some of the drugs approved for CIS are:

  • Avonex (interferon beta-1a)
  • Betaseron (interferon beta-1b)
  • Copaxone (glatiramer acetate)
  • Extavia (interferon beta-1b)
  • Glatopa (glatiramer acetate)
  • Mayzent (siponimod)
  • Tysabri (natalizumab)
  • Vumerity (diroximel fumarate)

Ask your neurologist about the potential benefits and risks of each before choosing to take one of these powerful medications.

With CIS, there’s no way to know for sure if you’ll eventually develop MS. You may never have another episode.

But if it appears that you’re at high risk of developing MS, you have a lot to consider.

The next step is to consult with a neurologist experienced in treating CIS and MS. Before making treatment decisions, it might be wise to seek a second opinion.

Whether you choose to take MS drugs or not, be sure to notify your doctor at the first sign of another episode.

MS affects everyone differently. It’s impossible to predict one person’s long-term outlook. After 15 to 20 years, one-third of people with MS have minimal or no impairment. Half have a progressive form of MS and increasing impairments.