Diagnosing Clinically Isolated Syndrome and MS
An episode of clinically isolated syndrome is often an indication that multiple sclerosis (MS) will develop in the future. Here we look at what is involved in diagnosing clinically isolated syndrome and what you can expect if you have this condition.
Clinically isolated syndrome (CIS) is a term used to describe the first time you experience a single episode of inflammation or demyelination (which is the loss of the protective covering [myelin] on nerve cells) in the brain or spinal cord that lasts 24 hours or longer. This episode can involve just one location (called a monofocal episode) or several sites (multifocal).
Seventy percent of people who experience clinically isolated syndrome are between the ages of 20 and 40, according to the National Multiple Sclerosis Society (NMSS). Clinically isolated syndrome affects the optic nerve, brainstem, or the spinal cord and can present with the following signs and symptoms (this is not a complete list):
- Reduced visual acuity in one eye
- Reduced color vision
- Eye pain, especially when you move your eyes
- Swelling of the optic nerve
- Loss of sensation in the face
- Ataxia (problems with coordination)
- Dysarthria (difficulty moving the muscles of the mouth, throat, vocal cords, etc.
- Weakness in one leg
- Incomplete transverse myelitis, inflammation of the spinal cord that can cause problems with bowel elimination, weakness in the limbs, and sensory deficits
- Positive Lhermitte’s sign (electrical sensations running down the back into the legs
About 80 percent of individuals who experience CIS go on to develop MS. That diagnosis can be made when the person experiences a second episode.
It’s important to get an accurate diagnosis of CIS so you can begin treatment. Acute treatment may include high doses of intravenous or oral corticosteroids for several days to address the inflammation.
To help reduce the chances of converting from CIS to MS and to reduce the risk of disability in the future, clinicians also turn to disease-modifying drugs. These include Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), and Extavia (interferon beta-1b), all of which have been approved by the Food and Drug Administration for this condition.
Once someone experiences clinically isolated syndrome, a magnetic resonance imaging (MRI) of the brain can help determine what the individual’s risk of developing MS will be. If the clinician sees lesions associated with MS, the risk is about 60 to 80 percent within 10 years, according to an article in The Neurohospitalist, although about 20 percent of people who show no lesions can get MS as well.
Other risk factors for developing MS after experiencing CIS include being nonwhite, age less than 30 years, smoking, and having an Epstein-Barr virus encoded nuclear antigen 1 titers.
In addition to an MRI, other tests to evaluate the likelihood of developing MS include evoked potentials and examination of the cerebrospinal fluid. Visual-, somatosensory-, and brain stem auditory-evoked potentials are measures of electrical activity in the central nervous system. Research has shown there is an increased risk of developing moderate disability from MS if all three evoked potential are abnormal at the time of CIS.
Tests involving the cerebrospinal fluid also can be used. Two of the tests that can be used were compared in a recent study involving more than 200 patients.
The tests were the oligoclonal bands (OCB) and measurement of immunoglobulin kappa free light chains (KFLC). Although the OCB test is the one most often used to support a diagnosis of MS and to help predict whether CIS will convert to MS, the test involves some difficult techniques.
Overall the authors found that the two approaches were somewhat similar in diagnostic sensitivity and specificity in people with early MS. KFLC may be a better option because it is easier to use.
Research has shown that starting disease-modifying treatment within three months of experiencing CIS reduces the risk of later developing MS. However, the research is less clear about the benefits of such treatment on reducing future disability.
For now, the bottom line appears to be that anyone who experiences clinically isolated syndrome should seek professional medical advice as soon as possible and take steps to reduce their chances of future disabilities and of developing MS.
Marcus JF et al. Updates on clinically isolated syndrome and diagnostic criteria for multiple sclerosis. The Neurohospitalist 2013 Apr; 3(2): 65-80
National Multiple Sclerosis Society
Pelayo R et al. Do multimodal evoked potentials add information to MRI in clinically isolated syndromes? Multiple Sclerosis 2010; 16(1): 55-61
Senel M et al. Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis. PLoS One 2014 Apr 2; 9(4): e88680