How many people with clinically isolated syndrome never progress to MS?

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. 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]
abstract