Medicine & Research

Most individuals with MS will begin their journey with relapsing-remitting MS. In fact, 85 percent of individuals living with MS present with this diagnosis. The starting point for RRMS is clinically isolated syndrome. CIS is the very first clinical attack or relapse of RRMS, but not every person who experiences a CIS will go on to develop MS. CIS may manifest as transverse myelitis, optic neuritis, or a brainstem syndrome. While these are the most common forms of CIS, there are countless other variations of CIS depending upon where in the central nervous system the lesion is. Let’s take a closer look at a few types of CIS and how we might predict who is at risk for developing MS after a CIS.

Transverse myelitis is inflammatory demyelination in the spinal cord. This could result in changes in sensation, weakness, in coordination, or changes in bladder and bowel function. Depending on whether the inflammation is in the cervical spinal cord or thoracic spinal cord, transverse myelitis may involve only the legs or both the arms and legs. Optic neuritis is inflammatory demyelination in the optic nerve. Optic neuritis typically results in blurred vision in the affected eye, loss of color (especially sensitivity to the color red), and pain with eye movement. Demyelination within the brainstem can cause double vision, facial weakness, trigeminal neuralgia, weakness, or incoordination.

Treatment and Prognosis

When a person presents with a CIS, there really are two issues: treatment and prognosis. A CIS is treated in the same way as an MS relapse, with options ranging from observation, to steroids, IVIG, or plasma exchange. The decision to treat or observe usually depends on the severity and functional limitations of the symptoms, and any comorbidities. Once an immediate treatment plan is in place, the next question is whether this person is at high risk for the development of MS. This risk is determined by the MRI findings, CSF exam, and clinical presentation. The diagnosis of RRMS has been defined as the dissemination of focal neurological events in time and space. Classically, this meant that a person had to have two relapses or attacks before a diagnosis of MS could be established. The danger in waiting for a second clinical attack before making an MS diagnosis lies in the presence of subclinical, or hidden, disease activity that occurs in between attacks. Some studies have suggested that for every clinical MS relapse we are aware of, there can be five to 10 new silent lesions on MRI.

Therefore, the challenge in evaluating the person with CIS is in determining how best to assess the risk quickly and accurately for MS. MS is currently diagnosed using the McDonald Criteria. Through these guidelines, we can use the clinical presentation, MRI, and CSF findings to make an MS diagnosis. In recent years, the McDonald Criteria have evolved to allow MRI lesions to count as clinical relapses. This has sped up the diagnosis of MS for many cases. It is possible to make the diagnosis of RRMS in a person presenting with CIS. If a CIS patient has evidence of both acute and older areas of demyelination on MRI, this satisfies the requirement for dissemination of neurological events in both time and space and establishes an MS diagnosis. The presence of even one brain MRI lesion typical for demyelination in the person with a CIS puts them into a higher risk group for MS. In some situations, a CSF examination may be pursued. If a person has evidence of oligoclonal bands in their spinal fluid, this will also put them into a high-risk group for developing MS. Oligoclonal bands are antibodies produced in the spinal fluid and are commonly seen in MS.

Symptoms and Precursors

While brain MRI and the CSF examination are the main factors that determine the risk of MS after CIS, we can also look at the presenting symptoms. How CIS presents clinically may give us some clues as to whether there is a higher risk for the development of MS. In transverse myelitis, milder symptoms (i.e. numbness without weakness) are associated with a higher risk for the future development of MS. If optic neuritis is present in one eye vs. both eyes, this is linked to a higher risk for the development of MS. While we typically think of RRMS as beginning with the first attack or CIS we know MS likely begins even earlier. Recent studies have shown that years before an MS diagnosis, people with MS visit their primary care doctors more frequently than people without MS. These visits are usually for nonspecific issues like fatigue or mood changes. So, there appears to be some type of clinical precursor that occurs in people with MS even before their first big attack.

Another possible early manifestation of MS is radiographic isolated syndrome. These are brain MRI changes typical for MS in the absence of symptoms. This situation may arise if a person has an MRI as part of an evaluation for headaches or a concussion. When the person with an RIS is followed over time, many will go on to have typical MS symptoms and an MS diagnosis later in life. Earlier, we discussed the acute treatment of a CIS with steroids, IVIG, or plasma exchange. We also need to consider long-term treatment to prevent future attacks. If a person is in a high-risk group for the development of MS or meets the McDonald Criteria for an MS diagnosis after a CIS, we should consider starting an MS disease-modifying therapy.

Research has been consistent in showing that the sooner we start therapy, the more likely we are to prevent disability in the future. We’ve come a long way since the days when a person presenting with their first demyelinating attack was told to go home and call if it happens again. We have better diagnostic tools, a better understanding about the insidious nature of MS and better treatment options. I know we all look forward to the day when we can stop MS in its tracks 100 percent of the time.