CIS - THE CLINICALLY ISOLATED SYNDROME

[Quixotic1]

CIS - the Clinically Isolated Syndrome

WHAT IS IT AND WHAT DOES IT MEAN?

With the growing evidence that the Disease Modifying Drugs are most useful in treating MS when they are used early in the course of the disease, there has been a flurry of research into what indications there might be to determine who is most at risk to develop Multiple Sclerosis.  Ideally we would like to be able to identify who really is at risk for MS when a patient shows up with suggestive symptoms.  The best way would be to have a blood test, that only MS patients had, but no one else had.  This would be called a "biomarker".  Unfortunately, despite intensive research, no suitable biomarker has yet been indentified.  We are left with trying to predict which patients who have early signs "suggestive of MS" will convert into "definite MS".  

Since RRMS (by far the most common kind) is characterized by symptoms and problems that occur in repeated attacks (Dissemination in Time) and by symptoms and problems that occur in different parts of the Central Nervous System, CNS (Dissemination in Space), our best bet is to look at those people who have only had their first attack.  This is a situation called a "Clinically Isolated Syndrome".  Waiting for a second attack may take many months or even many years.  We know from studies over the last 15 years that early treatment can help delay someone from having that second attack and getting those additional symptoms and problems that would make up the picture of full-blown MS?  How do we know which people with a CIS are most likely to "convert" from suspected MS to Definite MS?  Where can we look to make the best judgment so we can start treatment to prevent or substantially delay this conversion.

The diagnosis of MS requires that we find evidence that the disease has "acted up" on more than one occasion, more than 4 weeks apart.  This is called "Dissemination in Time".   This is what is missing in the person with CIS.  They have only had one attack.  This means that without further information we cannot make a diagnosis of MS.  The McDonald Criteria allows us to look at the MRI and, over time, find evidence that there is another attack on the central nervous system.  But, we want to predict as early as possible so we can treat and the MRI often does not yield enough information.   This is where the study data on CIS plays a role in predicting who will convert to MS.

Over the recent years, doctors and patients have used the term CIS to mean a variety of things - so much so that it has become a confusing term.  I found an comprehensive article published in the journal, Multiple Sclerosis, in 2008. (Mulitple Sclerosis 2008; 14: 1157-1174)  The method to explore this topic was to bring together 18 experts in the MS field from all over the world into a task force.  They met and worked on this in 2007.   They worked together to formulate some recommendations for the analysis and work up of a patient with CIS.  This group included some of the most well-known names in the field.  This was needed because the McDonlad Criteria - has not been the thorough diagnostic aid that some had hoped.  In fact, the Criteria have been most useful in "predicting" which patients who did not fulfill all the clinical requirements - of spread of the disease in time and space - were most likely to develop MS rather than being useful in "diagnosing people with MS."  In fact, many neurologists have misinterpreted the McDonald Criteria and misused it, as we have discussed so many times in the forum.


THE DEFINITION OF CIS

The task force felt that there were actually several "subtypes" or classes of CIS that had confused practitioners and that might have caused too much variability when they were lumped together in studies.  So, they proposed the following groups so that neurologists would have a clearer approach to diagnosis.

First they decided that the term CIS should ONLY  refer to the patient that had one, single attack of symptoms and signs that suggested an underlying inflammatory, demyelinating disease.  In general, this referred to the appearance of one or more symptoms which appeared fairly suddenly - over hours or days to maybe a week.  They defined the classes of CIS based on whether this first attack involved only one symptom, called "monofocal", such as an attack of optic neuritis without any other symptoms, whether there were two or more symptoms, called multifocal, like facial numbness and weakness of a limb, and whether there was associated MRI features consistent with demyelination.  They included one scenario, though, that had previously been ignored.  This was the patient who had no symptoms, or just very non-specific symptoms (like dizziness or headache), but somehow had MRI lesions found that suggested evidence of multifocal disease of a demyelinating type.  This means those people who have MRIs done for some other reason than looking for MS, like as a work up for headaches or after a head injury.

The Classes of CIS

First some definitions:

Mono = one

Focal = spot, place (monofocal - just one spot)

Multi = more than one (multifocal - more than one spot)

I     CIS - clinically monofocal, at least one asymptomatic MRI lesion.  This person has had one attack and has only one symptom suggestive of a demyelinating lesion in the CNS (for example hypereactive reflexes in one limb).  However, they also have at least one lesion on the MRI for which there is no correlating symptom.  That MRI lesion should be consistent with MS.

II     CIS - clinically multifocal, at least one asymptomatic MRI lesion.  This patient had had just one attack, but has indications that there are more than one demyelinating lesion in the CNS.  An example of this might be optic neuritis and L'Hermitte's Sign.  On the MRI there should be at least one lesion that doesn't have a corresponding lesion, ie. at least one asymptomatic MRI lesion.  The MRI lesion(s) should be consistent with MS or demyelination.

III    CIS - clinically monofocal, MRI may appear normal; no asymptomatic MRI lesions  This patient has had just the one appearance of a single symptom, like pain on eye movement with visual disturbance, and their MRI is normal; there is no asymptomatic MRI lesion.  Approximately one third (1/3) of all patients with CIS will have a normal baseline MRI.

IV    CIS - clinically multipfocal, MRI may appear normal; no asymptomatic MRI lesions  This patient has more than one symptom, for example facial numbness and a urinary urgency of a neurolgical type.  The task group deems this a "rare" occurrence, but the article does not elaborate, stating that they believe this is a rare occurence.

V    CIS - no clinical presentation (no attack) to suggest demyelinating disease, but MRI is suggestive.  An MRI done for some other reason happens to show multiple lesions that are suggestive of demyelination.  But the patient has had no symptoms OR they have had very non-specific symptoms like fatigue, headaches or dizziness.

con't below

[cali1892]

by dragon_flies, Jan 10, 2010 02:26PM
That was really interesting.

How do neurologists consider attacks that a patient had before coming into their care? As in, would I have to come to the neurologist when I'm having symptoms, wait for them to go away, and then return the next time I have symptoms in order to get a definite diagnosis? Or could they consider the numerous episodes that I've had in the past, and the symptoms that I'm having at present, and use that to determine dissemination in time? (I don't know if that makes sense - but I'll try to clarify if you want me to!) Would they likely diagnose me with CIS because this is the first episode that they're seeing, or just trust me when I tell them about the many previous times that I've had symptoms?


dragon_flies, that's a really good question.  I have often wondered about this.  Anyone?

[Mike_Shuswap]

Thanks moki b

       Mike

[mokibear]

bump

[dragon_flies]

That was really interesting.

How do neurologists consider attacks that a patient had before coming into their care? As in, would I have to come to the neurologist when I'm having symptoms, wait for them to go away, and then return the next time I have symptoms in order to get a definite diagnosis? Or could they consider the numerous episodes that I've had in the past, and the symptoms that I'm having at present, and use that to determine dissemination in time? (I don't know if that makes sense - but I'll try to clarify if you want me to!) Would they likely diagnose me with CIS because this is the first episode that they're seeing, or just trust me when I tell them about the many previous times that I've had symptoms?

[Joe79]

Bump

[Suzie9]

This was very interesting reading.

I have read up a lot on CIS and risk of conversion to clinical MS but this is definitely the most detailed information I have read and the easiest to understand.

It also puts me at higher risk than I thought (I am diagnosed with CIS with 4 lesions, 2 on my brain and 2 on my spine), but I like to keep informed and up to date so I have some idea of what to expect.

As I am in the UK DMD's are not an option for me but I am generally fit and well, only very minor problems so far.

For me it is 3 years since my initial attack (severe paresthesia around the spine). Although I have had other small problems that might have been considered a relapse, they were not typical and no change on MRI so there was nothing that would give me a diagnosis of MS. So its the waiting game as it is for many people.