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MS research update - Clinically isolated syndrome: how many people never progress to MS? - 06 August 2013


This research followed 246 people in Sweden who had an episode of neurological symptoms which lead to a diagnosis of clinically isolated syndrome (CIS). Most went on to be diagnosed with MS but almost one in five remained "CIS only" 50 years after their attack.

The researchers observed that, if someone had not converted from CIS to clinically definite MS after 25 years, there was almost no risk that they would convert at a later date.


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. Symptoms vary and may just be of one type, for example optic neuritis, or several different symptoms may occur together.

Not everyone who experiences CIS will go on to develop MS and for some there may be no further symptoms. How many people fall into this category is debatable. Previous research has given a range from 30% to 75% when following people for up to 30 years.

This research aimed to determine the probability of someone remaining with a diagnosis of CIS for their entire lifetime by following a group of people diagnosed with CIS in Sweden between 1950 and 1964. Some of the group were followed for over 50 years.

How this study was carried out

246 people in the study group were diagnosed with CIS between the ages of 10 and 56 (average age was 31). All of them were examined another three times over the following 25 years and then again in 2002 or 2003, many years after their initial attack. 41 of the group still showed no further evidence of MS-like disease and were classified as "CIS only".

A final examination of the "CIS only" group members took place in 2011. 27 had already died, due to cancer (14), vascular disease (11) and other causes (2). Three were not included in the final examination as they had suffered a stroke in the intervening years. The remaining 11 members of the "CIS only" group had an average age of 78 (age ranged from 67 to 90) and it was an average of 51 years (but ranged from 49 to 57 years) since their diagnosis with CIS. Eight were clinically examined and the other three were interviewed by phone.

What was found

The eight people with CIS who were clinically examined had minimal disability as judged by their EDSS scores which ranged from zero to two. There were no differences in cognitive performance compared with healthy controls of the same age group and no evidence of daytime sleepiness, fatigue or depression. Seven of the "CIS only" group, aged 67 to 90, and three healthy controls underwent an MRI scan which was evaluated according to the criteria for a diagnosis of MS.

The researchers concluded that almost one in five (18%) of the 236 members of the study group remained "CIS only" after 25 years. The other members of the group had gone on to have another attack and so were diagnosed with clinically definite MS. The last person to make this transition did so 24 years after their first attack. There was no difference between men and women in the risk of converting from CIS to MS.

The outcome was better for people whose first attack was optic neuritis as almost a third (30%) remained "CIS only" compared with 13% of those with other symptoms. In addition, their eyesight returned to almost its previous level.

Similarly, people with afferent CIS (sensory and optic symptoms) had a good prognosis, with 28% remaining "CIS only".

What does it mean?

The authors conclude that people who have afferent (sensory and optic) symptoms are more likely than others to remain "CIS only". Also, if someone had not converted from CIS to clinically definite MS after 25 years, then there was almost no risk that they would convert at a later date. This came from observations of people more than 50 years after the attack of neurological symptoms that had given them the diagnosis of CIS.

Novakova L, Skoog B, Runmarker B, et al.
Clinically isolated syndromes with no further disease activity suggestive of multiple sclerosis at the age of population life expectancy..
Mult Scler. 2013 Jul 18. [Epub ahead of print]

More about clinically isolated syndrome

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

Clinically isolated syndrome (CIS) may or may not go on to become clinically definite MS. Consequently, 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 A-Z.

Research by topic areas...

Symptoms and symptom management

De Ridder D, Van Der Aa F, Debruyne J, et al.
Consensus guidelines on the neurologist's role in the management of neurogenic lower urinary tract dysfunction in multiple sclerosis.
Clin Neurol Neurosurg. 2013 Jul 20.[Epub ahead of print]

Kalron A, Dvir Z, Frid L, et al.
Quantifying gait impairment using an instrumented treadmill in people with multiple sclerosis.
ISRN Neurol. 2013 Jun
Read the full text of this paper

MS relapses

Berkovich R.
Treatment of acute relapses in multiple sclerosis.
Neurotherapeutics. 2013 Jan;10(1):97-105.

Disease modifying treatments

Outteryck O, Ongagna JC, Brochet B, et al.
A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.
Eur J Neurol. 2013 Jun 12.

Other treatments

Rabadi MH, Kreymborg K, Vincent AS.
Sustained-release fampridine (4-Aminopyridine) in multiple sclerosis: efficacy and impact on motor function.
Drugs R D. 2013 Jul 20. [Epub ahead of print]


Skår AB, Folkestad H, Smedal T, et al.
"I refer to them as my colleagues": the experience of mutual recognition of self, identity and empowerment in multiple sclerosis.
Disabil Rehabil. 2013 Jul 26. [Epub ahead of print]

Kalron A, Greenberg-Abrahami M, Gelav S, et al.
Effects of a new sensory re-education training tool on hand sensibility and manual dexterity in people with multiple sclerosis.
NeuroRehabilitation. 2013 Jan 1;32(4):943-8.

Co-existing conditions

Fromont A, Binquet C, Rollot F, et al.
Comorbidities at multiple sclerosis diagnosis.
J Neurol. 2013 Aug 2. [Epub ahead of print]

Marrie RA, Yu BN, Leung S, et al.
The utility of administrative data for surveillance of comorbidity in multiple sclerosis: a validation study.
Neuroepidemiology. 2013;40(2):85-92.
Read the full text of this paper

Assessment tools

Baumstarck K, Butzkueven H, Fernández O, et al.
Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.
Health Qual Life Outcomes. 2013 Jul 29;11(1):127. [Epub ahead of print]
Read the full text of this paper

Pilutti LA, Dlugonski D, Sandroff BM, et al.
Further validation of multiple sclerosis walking scale-12 scores based on spatiotemporal gait parameters.
Arch Phys Med Rehabil. 2013 Mar;94(3):575-8.

Causes of MS

Strautins K, Tschochner M, James I, et al.
Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk.
Mult Scler. 2013 Jul 25. [Epub ahead of print]

Hedström A, Hillert J, Olsson T, et al.
Reverse causality behind the association between reproductive history and MS.
Mult Scler. 2013 Jul 25. [Epub ahead of print]

Psychological aspects

Sumowski JF, Leavitt VM.
Cognitive reserve in multiple sclerosis.
Mult Scler. 2013 Aug;19(9):1122-7.

Physical activity

Klaren RE, Motl RW, Dlugonski D, et al.
Objectively quantified physical activity in persons with multiple sclerosis.
Arch Phys Med Rehabil. 2013 Jul 29. [Epub ahead of print]

Feltham MG, Collett J, Izadi H, et al.
Cardiovascular adaptation in people with multiple sclerosis following a twelve week exercise programme suggest deconditioning rather than autonomic dysfunction caused by the disease: Results from a randomized controlled trial.
Eur J Phys Rehabil Med. 2013 Jul 23. [Epub ahead of print]
Read the full text of this paper


Runia TF, Jafari N, Hintzen RQ.
Application of the 2010 revised criteria for the diagnosis of multiple sclerosis to patients with clinically isolated syndromes.
Eur J Neurol. 2013 Jul 30. [Epub ahead of print]

Chruzander C, Johansson S, Gottberg K, et al.
A 10-year follow-up of a population-based study of people with multiple sclerosis in Stockholm, Sweden: Changes in disability and the value of different factors in predicting disability and mortality.
J Neurol Sci. 2013 Jul 26. [Epub ahead of print]

Pregnancy and childbirth

Ghezzi A, Annovazzi P, Portaccio E, et al.
Current recommendations for multiple sclerosis treatment in pregnancy and puerperium.
Expert Rev Clin Immunol. 2013 Jul;9(7):683-92.


Dibble LE, Lopez-Lennon C, Lake W, et al.
Utility of Disease-specific measures and clinical balance tests in prediction of falls in persons with multiple sclerosis.
J Neurol Phys Ther. 2013 Jul 18. [Epub ahead of print]

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