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Clinically isolated syndrome (CIS)

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  1. What is clinically isolated sydrome?
  2. What causes CIS?
  3. How is CIS diagnosed?
  4. What are the symptoms I might experience
  5. How is CIS treated?
  6. What is the risk of developing MS following CIS?
  7. Can disease modifying drugs delay onset of MS in people at high risk?
  8. Are there lifestyle changes I can make that might help reduce the risk?
  9. Living with uncertainty
  10. Radiologically isolated sydrome (RIS)

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that lasts for at least 24 hours. Although some people never go on to experience further neurological symptoms, in others CIS can be the first sign of what may later 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 just one area of the brain or spinal cord (monofocal) resulting in a single symptom, such as optic neuritis which affects the eyes, or it may occur in several places (multifocal), which can lead to more symptoms, for example dizziness and bladder problems.

Not everyone who experiences CIS goes on to develop MS, figures vary from 1 in 5 people up to 4 in 5, so it is possible that you may never have any further symptoms. It's difficult to predict who will go on to have further episodes, but 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 at the time of the CIS, the higher your risk of developing MS in the future.

Studies have shown that early treatment of CIS with disease modifying drugs can delay a second episode if you're at high risk of developing MS.

What is clinically isolated sydrome?

Clinically isolated syndrome (CIS) is the term used to describe your first episode of neurological symptoms that last for at least 24 hours and isn't caused by anything else - such as a fever or infection. CIS can be the first sign of what may subsequently turn out to be multiple sclerosis. You may never go on to experience further symptoms, but if an MRI scan shows several areas of damage (lesions) to your brain and/or spinal cord 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 your brain and spinal cord (the central nervous system). 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 aren't known yet.

How is CIS diagnosed?

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

Medical history

Sometimes an earlier episode of symptoms, such as numbness can prove significant as it could suggest a previous episode of neurological symptoms which you may not have thought much of at the time. Evidence of a previous episode could lead to 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

At the moment there is no blood test that can be used to diagnose either MS or CIS. However, blood tests might be carried out to identify, or rule out, other potential causes for your symptoms.

MRI scan

The most common test used is a scan of the brain and/or spinal cord using MRI. MRI can detect the tiny scars or lesions caused by demyelination which show up as little white patches on the scan 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 older areas of scarring that might exist.

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

What are the symptoms I might experience

The symptoms you experience will depend on where in the brain or spinal cord damage has occurred. 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.

Optic neuritis is a condition in its own right and not everyone who experiences optic neuritis goes on to develop other symptoms of MS.

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.

Transverse myelitis can also be a condition in its own right and in most cases a person only has a single episode.

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 damage to the nerves in the brainstem -  the area at the base of the brain where it connects to the spinal cord. The brainstem controls basic functions such as your breathing, heart rate and blood pressure. Symptoms of brainstem syndrome include dizziness or vertigo, nausea, vomiting and double vision, but symptoms vary depending on the specific area affected.

Other symptoms

Symptoms such as fatigue and problems with thinking and memory can also be experienced as part of CIS.

How is CIS treated?

Many CIS episodes are mild and resolve on their own 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 in hospital, but only for a few days. Steroids can speed up your recovery - however, your level of recovery will be the same whether you have steroid treatment or not.

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

If you're at a higher risk of developing MS, your neurologist may give you the choice of taking a disease modifying drug (DMD).

What is the risk of developing MS following CIS?

To make a diagnosis of MS, the neurologist is looking for evidence you have two or more areas of damaged myelin in different parts of your brain and/or spinal cord. This damage will need to 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've experienced a multifocal clinically isolated syndrome, although damage may have occurred in more than one place, it has still only happened at one point in time, so you wouldn't be given a diagnosis of MS if there is no evidence of a previous episode.

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's no single test that can definitively determine whether you'll go on to develop MS or not after experiencing CIS. Many factors have been investigated to see if they can better determine your risk, including:

  • your age
  • your ethnicity
  • where you live
  • the number, location and size of lesions seen on an MRI scan
  • levels of various different proteins in your serum, blood or the fluid surrounding the spinal cord (CSF)
  • vitamin D levels
  • the symptoms you experienced during your CIS.

Of these, MRI findings are the most useful tool to determine your risk of developing MS. Other strong predictors are being older at the time of your CIS, or if oligoclonal bands are detected in the cerebrospinal fluid.

The diagnostic criteria for MS were updated in 2017. These changes have made them more sensitive and led to less diagnostic uncertainty, which means that more people are being diagnosed earlier with MS and fewer people are being given a diagnosis of CIS.

Can disease modifying drugs 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, Extavia) and glatiramer acetate (Copaxone) can delay conversion to MS in people at high risk. The goal of treatment is to delay the onset of additional episodes, which are known as relapses. Relapses are the sudden onset of new symptoms or the worsening of existing symptoms. The disease modifying drugs work with different parts of the immune system to reduce the inflammation caused by MS to the nerve cells in the brain and spinal cord. This helps reduce the number and severity of relapses.

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) and cladribine (Mavenclad) are also beneficial in delaying conversion to MS, but they're not currently licensed for use in CIS in the UK.

Making a decision about treatment

As there's no conclusive way of knowing whether you will go on to develop MS after experiencing a clinically isolated syndrome, making a decision about whether to go on treatment or not 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. However 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?

Are there lifestyle changes I can make that might help reduce the risk?

There is evidence that smokers with CIS have a higher risk of developing MS than non-smokers. So the best advice is to stop smoking if you are a smoker.

Some studies suggest that low levels of vitamin D can increase your risk of converting from CIS to MS. If you have low levels of vitamin D you may want to consider taking a vitamin D supplement, although it's not yet clear whether taking supplements is effective.

Other lifestyle changes that can help you stay as well as possible include eating healthily to maintain a health weight, and staying as active as possible.

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. Research has shown that there is an increased risk of mild to moderate depression and anxiety in those with CIS. 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. If this isn't the case for you, it's important to contact your GP or neurologist if you experience new symptoms that could potentially lead to a diagnosis of MS.

Radiologically isolated sydrome (RIS)

A neurologist can also make a diagnosis of radiologically isolated syndrome (RIS). This is when someone who has not had any MS symptoms has had an MRI scan for another reason (for example following a trauma or if you experience migraines) and brain or spinal cord lesions compatible with MS have shown up in that scan. 

References

  • 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
  • Grzegorski T, Losy J. What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update. Reviews in the Neurosciences 2019; Dec 7 [Epub ahead of print]. Summary
  • Rintala A, et al. Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis. Journal of Psychosomatic Research 2019;124:109761. Summary
  • Miller AE, et al. Long-term outcomes with teriflunomide in patients with clinically isolated syndrome: results of the TOPIC extension study. Multiple Sclerosis and Related Disorders 2019;33:131-138. Full article
  • Metz LM. Clinically isolated syndrome and early relapsing multiple sclerosis. Continuum (Mineapp Minn) 2019;25(3):670-688. Summary
  • Hartung HP, et al. Long-term follow-up of multiple sclerosis studies and outcomes from early treatment of clinically isolated syndrome in the BENEFIT 11 study. Journal of Neurology 2019; Jan 4 [Epub ahead of print] Summary
  • Gaetani L, et al. 2017 revisions of McDonald criteria shorten the time to diagnosis of multiple sclerosis in clinically isolated syndromes. Journal of Neurology 2018;265(11):2684-2687. Summary
  • Eran A, et al. MRI in predicting conversion to multiple sclerosis within 1 year. Brain and Behavior 2018;8(9):e01042. Ful article
  • Shaheen HA, et al. Does vitamin D deficiency predict early conversion of clinically isolated syndrome? A preliminary Egyptian study. International Journal of Neuroscience 2018;128(10):946-951. Summary
  • van der Vuurst de Vries RM, et al. Smoking at time of CIS increases the risk of clinically definite multiple sclerosis. Journal of Neurology 2018; 265(5):1010-1015. Full article
  • Armoiry X, et al. Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis. Journal of Neurology 2018;265(5):999-1009. Full article
  • O’Connell K, et al. Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: a double-blind randomised controlled trial. Multiple Sclerosis Journal – Experimental, Translational and Clinical 2017;3(3): 20555217317727296. Full article
  • van der Vuurst de Vries RM, et al. Fatigue after a first attack of suspected multiple sclerosis. Multiple Sclerosis 2018;24(7):974-981. Full article
  • Kappos L, et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology 2016;87(10):978-987. Full article
  • Pokryszko-Dragan A, et al. Cognitive performance, fatigue and event-related potentials in patients with clinically isolated syndrome. Clinical Neurology and Neurosurgery 2016;149:68-74. Summary
  • Borràs E, et al. Protein-based classifier to predict conversion from clinically isolated syndrome to multiple sclerosis. Molecular and Cellular Proteomics 2016;15(1):318-328. Full article
  • Kuhle J, et al. Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study. Multiple Sclerosis 2015;21(8):1013-1024. Summary
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