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Clinically isolated syndrome (CIS) is a first episode of neurological symptoms lasting at least 24 hours. Although there may not yet be enough information to identify the underlying cause of symptoms, CIS can be an indicator of what may turn out to be multiple sclerosis.

CIS is caused by damage to the covering of nerves in the central nervous system (CNS). Damage may occur in one place (monofocal) resulting in a single symptom (eg optic neuritis) or more than one place (multifocal), which can lead to different symptoms (eg dizziness and bladder problems).

Not everyone who experiences CIS goes on to develop MS, figures vary from 30% to 70%, so it may be that you never have any further symptoms. MRI scans can give a good idea of your risk of going on to develop MS. The more areas of damage seen on an MRI scan, the higher the risk of developing MS.

Research suggests that early treatment of CIS with disease modifying drugs can delay conversion to MS if you are at a high risk. The ABN guidelines state that neurologists may consider the use of beta interferon or glatiramer acetate for people within 12 months of a clinically isolated syndrome when MRI scans suggest a high chance of further episodes.

What is clinically isolated syndrome (CIS)?

Clinically isolated syndrome (CIS) is the term used to describe your first episode of neurological symptoms that last for at least 24 hours and are not caused by anything else (such as a fever or infection). This can be an indicator of what may turn out to be multiple sclerosis. You may never go on to experience further symptoms, but if an MRI scan shows brain lesions that are similar to those seen in MS then your chances of having further episodes and ultimately a diagnosis of MS are higher.

What causes CIS?

CIS is caused by inflammation and damage to myelin, the protective fatty substance that surrounds nerve cells in the central nervous system (brain and spinal cord). This damage (called demyelination) disrupts the way nerve messages are carried to and from the brain and results in the symptoms you experience. The reasons why this happens are as yet unknown.

How is CIS diagnosed?

A neurologist makes the diagnosis of clinically isolated syndrome. There is no one examination or test that can be used to diagnose CIS and the process involves ruling out other possible causes of your symptoms. Your medical history and a clinical examination are also important.

Medical history

Sometimes an earlier episode of symptoms, such as numbness which might have been treated without recognising its importance at the time, can prove significant as it could suggest a previous episode of neurological symptoms and consequently, a diagnosis of MS.

Neurological examination

There are a number of simple tests that a neurologist can carry out that can suggest, or rule out, a cause for your symptoms. These include checks on your movement, coordination, vision, balance, reflexes and other functions of the senses. Information from these tests can determine whether you might have CIS and where in your central nervous system damage has occurred.

Blood tests

These may be used to identify or rule out any other potential causes for your symptoms. At the moment there is no blood test that can be used to diagnose either MS or CIS.

MRI scan

The most common test used is a scan of the brain and/or spinal cord using MRI. This scan can detect the tiny scars or lesions caused by demyelination which show up as little white patches on the image. Sometimes a dye called gadolinium is injected into a vein before your scan as it can help the radiologist and neurologist distinguish between active areas of inflammation and any previous areas of scarring that might exist.

The areas where damage is most frequently seen are the optic nerve, the spinal cord, and the brainstem.

What are the symptoms I might experience?

Common symptoms experienced by someone with CIS include:

Optic neuritis

Optic neuritis is caused by damage to the optic nerve which transmits images from the retina at the back of the eye to the brain. It can occur suddenly or over a period of hours. Optic neuritis commonly causes blind spots or areas of poor vision surrounded by an area of normal vision. Your colour vision can also be severely affected and you may experience pain, particularly during eye movement.

Transverse myelitis

Transverse myelitis occurs when there is damage affecting the spinal cord. The onset of symptoms may be sudden - developing over one to two hours, or more gradual - over one to two weeks. The area of the spinal cord which is damaged will determine what symptoms you experience and which parts of your body are affected. Common symptoms include muscle weakness, abnormal sensations in the toes and feet such as numbness or tingling, and bladder or bowel problems.

Lhermitte's sign 

Lhermitte's sign (sometimes referred to as barber's chair syndrome) is a sudden sensation resembling an electric shock that passes down the back of your neck and into your spinal column and can radiate out to your fingers and toes. It is usually triggered by flexing your neck (bending your head down, chin towards chest) and is associated with lesions at the top of the spinal cord.

Brainstem syndrome

Brainstem syndrome occurs when there is demyelination of nerves in the brainstem - this is the area at the base of the brain that connects to the spinal cord. The brainstem controls basic functions such as your breathing, heart rate and blood pressure. Symptoms you might experience during a brainstem syndrome include nausea, vomiting and double vision, but symptoms vary depending on the specific area affected.

How is CIS treated?

Many CIS episodes are mild and resolve of their own accord over a period of weeks. However when symptoms are more severe, for example visual loss and pain in optic neuritis, or vertigo where there is a brainstem lesion, you may be prescribed high dose steroids. These are given either as a pill or through a drip, but only for a few days. Steroids can speed up your recovery - however, your level of recovery will be the same with or without steroid treatment.

Where it is necessary, you may also be prescribed treatments for specific symptoms.

What is the risk of developing MS?

To make a diagnosis of MS, the neurologist is looking for evidence you have two or more areas of damage to your myelin in different parts of your central nervous system that have occurred at different points in time. Clinically isolated syndrome refers to a single point in time – it is just one episode of neurological symptoms. If you have experienced a multifocal clinically isolated syndrome, damage may have occurred in more than one place, but it has still only happened at one point in time.

The evidence of damage to your myelin may be seen clinically – as an episode of neurological symptoms lasting more than 24 hours - or on an MRI scan. A diagnosis of MS may be made on the basis of one clinical episode if an MRI scan shows evidence of a previous attack.

There is no single test that can conclusively determine if you have experienced a clinically isolated syndrome whether you will then go on to develop MS or not. Many factors have been investigated including environmental factors such as levels of vitamin D, clinical signs and MRI. Of these, MRI findings are the most useful tool to determine your risk of conversion to MS.

Lesions on MRI

The presence of one or more lesions on an MRI scan indicates areas of demyelination, the more lesions there are the higher the risk is of experiencing a further attack and developing clinically definite MS. Studies have shown that the long-term risk for developing clinically definite MS is around 20% (1 in 5) when the scan shows only the lesion(s) associated with the CIS event itself, but this increases to 60-80% when other lesions are present on MRI.

Presence of oligoclonal bands on lumbar puncture

This is a less useful predictive tool than MRI and is not routinely carried out in cases of CIS. A lumbar puncture is a test where a small amount of the fluid which surrounds the brain and spinal cord is extracted. This is analysed in the laboratory and if more protein bands are seen than usual (called oligoclonal bands) this can be suggestive of a higher risk of conversion to MS.

Clinical features

Some symptoms that can be experienced during a CIS are thought to be associated with an increased risk of converting to MS compared to others. For example, sensory symptoms, such as numbness, tingling, or visual problems are thought to be associated with a lower risk of developing MS than symptoms that affect movement such as weakness.

Can treatment delay onset of MS in people at high risk?

Research has shown that early treatment of clinically isolated syndrome with disease modifying drugs such as the beta interferons (Avonex, Rebif, Betaferon, Extavia) and glatiramer acetate (Copaxone) can delay conversion to MS in people at high risk.

These drugs are available for prescription on the NHS in England and Wales for MS. The 2015 Association of British Neurologists (ABN) prescribing guidelines state that neurologists may consider the use of beta interferon or glatiramer acetate for people within 12 months of a clinically isolated syndrome when MRI evidence predicts a high likelihood of recurrent episodes.

More recent studies suggest that teriflunomide (Aubagio) shows similar results.

Making a decision about treatment

As there is no conclusive way of knowing whether you will go on to develop MS after experiencing a clinically isolated syndrome, making a decision about treatment can be difficult. There is the possibility that you might choose to have treatment when actually you would never go on to experience another episode, but you need to weigh this against the benefit that early treatment has in delaying the conversion to MS if your risk is high.

It can be helpful to understand both the benefits and the potential side effects associated with the disease modifying drugs and the need for long-term continuous treatment. 

Conversations with your neurological team, asking questions and getting all the answers you need are vital.

Key questions might include:

1. What are my options?

2. What are the pros and cons of each option?

3. How do I get support to help me make a decision that is right for me?

Living with uncertainty

If you have experienced CIS, living with the uncertainty of whether you will go on to develop MS or not can cause anxiety, fear, confusion or even anger. It can feel frustrating that health professionals can't say what you might expect to happen in the short or longer term.

However, having access to reliable information so you are fully informed about the condition and can make the right decisions for you is important. In some areas MS nurses are available to support people diagnosed with CIS.


  • Miller D, et al. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurology 2005;4(5):281-288. Summary
  • D'Alessandro R, et al. Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study. Journal of Neurology 2013;260(6):1583-1593. Summary
  • Kappos L, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006;67(7):1242-1249. Summary
  • Comi G, et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009;374(9700):1503-1511. Summary
  • Association of British Neurologists (ABN). Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Practical Neurology 2015;15(4):273-279. Full guideline
  • Fisniku LK, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008;131(3):808-817. Summary
  • Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria. Annals of Neurology 2011;69(2):292-302. Summary
  • Montalban X, et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology 2010;74(5):427-434. Summary
  • Scalfari A, et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain 2010;133(7):1914-1929. Summary
  • Gal RL, et al. Corticosteroids for treating optic neuritis. Cochrane Database of Systematic Reviews 2012;4:CD001430. Summary
  • Scott TF, et al. Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011;77(24):2128-2134. Summary
  • Confavreux C, Vukusic S. Natural history of MS: a unifying concept. Brain 2006;129(3):606-616. Summary
  • Taylor BV, et al. Latitudinal variation in incidence and type of first central nervous system demyelinating events. Multiple Sclerosis 2010;16(4):398-405. Summary
  • Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Archives of Neurology 2008;65(6):727-732. Summary
  • Tintoré M, et al. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis? Neurology 2008;70(13 pt2):1079-1083. Summary
  • Tintoré M, et al. Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 2006;67(6):968-972. Summary
  • Rojas JI, et al. Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis. Journal of Neurology 2010;257(7):1188-1191. Summary
  • Jacobs LD, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. New England Journal of Medicine 2000;343(13):898-904. Summary
  • Comi G, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001;357(9268):1576-1582. Summary
  • Comi G. Clinically isolated syndrome: the rationale for early treatment. Nature Clinical Practice. Neurology 2008;4(5):234-235.
  • Montalban X, Sastre-Garriga J. Diagnosis and trials of clinically isolated syndrome. Lancet Neurology 2014;13(10):962-963.
  • Miller DH, et al. Clinically isolated syndromes. Lancet Neurology 2012;11(2):157-169. Summary

Last updated: 08 February 2017

Last reviewed: 22 March 2016
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