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MS research update - Clinically isolated syndrome: is it possible to predict who will go on to develop MS? - 16 February 2015

Summary

Clinically isolated syndrome (CIS) is an individual's first episode of neurological symptoms. For some people, it turns out to be the first indication of MS, however not everyone who experiences CIS will go on to develop MS. Several potential risk factors have been associated with a higher risk of developing MS. This study looks at these risk factors in people with CIS to see if anything could be identified that could be used to predict which people diagnosed with CIS would go on to develop MS later.

Information on 1,047 people diagnosed with clinically isolated syndrome (CIS) was collected from 33 clinics in 17 countries. 623 (60%) of the people diagnosed with CIS went on to develop MS.

The study found that people diagnosed with CIS are at higher risk of later being diagnosed with MS if they had oligoclonal bands in their cerebrospinal fluid, had two or more lesions on their MRI brain scan and were young at the time they were diagnosed with CIS.

It was also found that low levels of vitamin D also put people with CIS at a higher risk of developing MS. Further studies would be needed to investigate the role of vitamin D to work out if the levels were causing MS or are a consequence of what happens to the body when MS starts to develop.

The authors conclude that their study shows that as oligoclonal bands and brain lesions increase the risk of developing MS and both of these are linked to immune system activity, it supports the case for targeting the immune system when someone is diagnosed with a CIS as this may delay or prevent MS developing.

Background

Clinically isolated syndrome (CIS) is an individual's first episode of neurological symptoms lasting at least 24 hours. For some people, it turns out to be the first indication of MS, however not everyone who experiences CIS will go on to develop MS and for some there may be no further symptoms.

The cause of MS is not well understood, but it seems that genetic and environmental factors come together, to trigger MS in an individual. Several potential risk factors have been associated with a higher risk of developing MS. Studying these further in people who have been diagnosed with CIS could help determine not only who with CIS is at higher risk of developing MS so they can be treated accordingly but it could also shed valuable light on the biology underlying MS and help prevent it developing in the first place. Previous research has looked at one or two of these risk factors in people with CIS, this study aimed to look at all of them together in the same people with CIS to look for any patterns.

How this study was carried out

Information on 1,047 people diagnosed with clinically isolated syndrome (CIS) was collected from 33 clinics in 17 countries. Data collected included age, gender, the symptoms caused by the first attack and number of lesions visible on the brain scans. Levels of vitamin D, oligoclonal bands and Epstein-Barr virus and cytomegalovirus antibodies were also measured.

All the people diagnosed with CIS were followed up for at least two years after their initial attack. The median follow up period for the whole group was 4.31 years. The average age was around 32 years old, two thirds of the group were female and three quarters (75%) had oligoclonal bands in their cerebrospinal fluid. 623 (60%) of the people diagnosed with CIS went on to develop MS.

The researchers used all of this information to see if they could identify anything that could be used to predict which people diagnosed with CIS would go on to develop MS.

What was found

The study found that people diagnosed with CIS are at higher risk of later being diagnosed with MS if they had oligoclonal bands in their cerebrospinal fluid, had two or more lesions on their MRI brain scan and were young at the time they were diagnosed with CIS.

It was also found that low levels of vitamin D also put people with CIS at a higher risk of developing MS. The study results suggested that people with lower levels of vitamin D tended to develop MS more quickly.

No consistent relationship could be found in relation to Epstein-Barr virus and cytomegalovirus antibodies and risk of MS.

What does it mean?

The study was the largest one to date to look at people diagnosed with CIS and to look at many risk factors for developing MS at the same time in them. The researchers do state that some of the results should be viewed with caution. In particular the vitamin D levels were only measured once and they did not ask about the amount of time people spent outside or vitamin D consumption through the diet. They also did not take into account many other factors thought to be involved in the development of MS including genetics and smoking.

The authors suggest that further studies would be needed to investigate the role of vitamin D to work out if the levels were causing MS or are a consequence of what happens to the body when MS starts to develop.

The authors conclude that their study shows that as oligoclonal bands and brain lesions increase the risk of developing MS and both of these are linked to immune system activity, it supports the case for targeting the immune system when someone is diagnosed with a CIS as this may delay or prevent MS developing.

Kuhle J, Disanto G, Dobson R, et al.
Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study..
Mult Scler. 2015 Feb 13. pii: 1352458514568827. [Epub ahead of print]
abstract

More about clinically isolated syndrome

Clinically isolated syndrome is an individual's first episode of neurological symptoms lasting at least 24 hours and can be an indicator of what may turn out to be multiple sclerosis. It is caused by inflammation or damage to the covering of nerve in one or more sites in the central nervous system.

Damage may occur in one place (monofocal) resulting in the experience of a single symptom (eg optic neuritis) or more than one place (mutifocal) when multiple symptoms might be experienced (eg incoordination and bladder symptoms).

As clinically isolated syndrome may or may not go on to become clinically definite MS, decisions about ongoing monitoring and treatment can be difficult to make.

Some studies have suggested that starting disease modifying treatment after a clinically isolated syndrome delays the onset of MS. In spite of this evidence, the use of disease modifying drug treatment after a clinically isolated syndrome remains controversial. The Association of British Neurologists produced guidelines for the prescribing of interferon beta and glatiramer acetate in 2009. Use of disease modifying drugs after a clinically isolated syndrome is only recommended if there is also MRI evidence suggesting a high likelihood of developing MS. Some of the possible benefits and risks of treating CIS are set out in our factsheet.

You can read more about Clinically isolated syndrome (CIS) in the A to Z of MS.

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