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

[jumpinjiminy]

Very nicely done. As always, excellent info. I guess mine falls into the rare type 4 category. But I think that's because I had many mild episodes over the years that went unreported and undetected. I didn't report any of it to an MD until it was in-your-face obvious. By that time, many things had accumulated.

[nikki861]

I actually asked my neuro about this today. He told me not to believe everything I read. I told him I dont read trash! I read FACTS!! He is not ready to commit to MS. Just told me he feels 85% sure MS. He said do these 3 days of steriod infusion and lets see how you feel. You are going to feel better than you have in 5 years!! Ok, great, then what??????????

[Quixotic1]

Bump for all the people who are asking about Clinically Isolated Syndrome.

Quix

[MisterTimC]

DocQ:
You are amazing!
Thanks for such great info.
TimC

[jdcatt]

I have a question for you Quix. I had what I believe was optic neuritis in 2003. I went to an ophthalmologist and to the ER and neither place diagnosed me. Both places said they didn't know what it was because nothing showed up on physical exam nor on CAT scan. I do however have a CAT scan from 2003 that was performed for eye pain.

I saw a neurologist about two days after my ER visit because I had developed severe vertigo and lost the hearing in one ear. I was in such bad shape physically and mentally that I didn't mention the eye pain that I had to him, at least I don't remember mentioning it. I was so focused on my vertigo and was so scared about the hearing loss that those two things were all I could focus on. The entire back side of my body went numb also and I don't believe that was entered into my history but that was the neuro's doing. I told him about it but he told me he had no idea what that could have been and wrote nothing on my chart.

My question is this...since I didn't receive an actual diagnosis of optic neuritis and my numbness was not entered into my chart does that mean that I now have no way of having those entered into my medical history? How does that work?

I ask because I believe I experienced a CIS at that time.

Thank you for any time you can give to my question.

[Pablo_Morphy]

This is an amazing amount of information.  Thank you so much, Quix!!!