Why Earlier Detection of MS is Possible
After much debate over the years about early treatment of multiple sclerosis, medical recommendations now strongly advocate for early intervention with drug therapy, known as Disease Modifying Therapy (DMT). Earlier detection of MS enables earlier intervention. Technological advancements have enabled earlier detection, and as a result, the diagnostic criteria have been modified. An MS diagnosis now can be made alone on MRI imaging and a Cerebrospinal Fluid (CSF) analysis.
New subclassifications of MS have accompanied early detection. That includes RIS (Radiologic Isolated Syndrome) and CIS (Clinically Isolated Syndrome). (For more information on the types of MS, read our recent blog here). These new classifications identify those at risk for developing MS sooner. Clinical studies (which we cover in more detail below) suggest that early DMT intervention can decrease the percentage of high-risk patients who go on to develop MS. As a result, early detection and consideration of MS therapies has been prioritized by treating physicians.
Treatment of Patients Diagnosed with RIS
When MRI abnormalities typical of MS are incidentally detected on scans, patients are diagnosed with RIS. Often a brain MRI is performed for symptoms that are not suggestive of MS, such as a migraine. Instead, the MRI reveals the appearance of central nervous system demyelination, consistent with MS. However, these individuals have not manifested clinical symptoms of MS.
Up to half of RIS patients will suffer their first clinical MS symptoms within three years. In one study, treatment of RIS patients with Dimethyl fumarate (DMF) effectively reduced the risk of MS progression. Compared to the placebo, the study found that the risk of a first acute event or a progressive clinical event was reduced by more than 80 percent. Of note, RIS is not yet a recognized subclassification of MS, though the debate ensues.
Early Treatment of MS for CIS Patients
What is considered less controversial is starting CIS patients with DMT. Unlike RIS, CIS is a recognized subclassification of MS. A CIS diagnosis refers to patients with no prior history of MS presenting with their first clinical attack resembling a typical MS flare. The diagnostic criteria are that the symptoms last at least 24 hours and are not associated with infection or fever.
The presentation can be focal (just one symptom related to one lesion) or multifocal (more than one lesion presenting with more than one symptom). The symptoms of CIS can include vision problems (such as double vision), dizziness, numbness, tingling, muscle stiffness or weakness, incoordination, difficulty walking, urinary or fecal incontinence, and sexual dysfunction. These are the same symptoms typically seen in MS, but in CIS they occur only once. If they occur again, patients are diagnosed with MS. (For more information on CIS diagnosis, go here.)
The CIS diagnosis may – or may not – advance to clinical MS. The appearance of demyelination (stripping of the coating of the nerve cells in the brain) on MRI scans is what determines the risk of converting from CIS to clinically definitive MS (CDMS). Patients with MRI lesions have a 60% to 80% chance of a second clinical event and therefore being diagnosed with MS. For those without MRI-detectable brain lesions, the risk of progressing to an MS diagnosis is significantly lower. Only 20% go on to be diagnosed with MS.
Effect of Drug Therapy for CIS patients
Recent drug trials have studied the effect of drug therapy after the onset of CIS. Two trials, the BENEFIT and CHAMPIONS extension trials, studied the anti-inflammatory drug interferon beta-1a’s (IFN-β) effect on progression to MS. The results highlight the disadvantage of postponed intervention. Delaying treatment by two to three years after the initial CIS diagnosis significantly increases the chance to convert to MS in five to ten years. In contrast, patients treated with IFN-β at the onset of CIS fared much better. A third study, CHAMPS, found that IFN-β’s treatment delayed the transition to CDMS by 55%. (Source).
These trials have been pivotal in changing the paradigm of when to begin disease modifying therapy. The benefits of early treatment are greatest for those with a poorer prognosis. Some patients with CIS however will never go on to have a second demyelinating event or symptoms. As there is no way to predict who will have the least active disease, using the treat-early strategy means that some patients will be on these medications for many years when they might not have had more active disease without the treatment.
Other clinical trials have studied the ideal time to begin DMT in high-risk CIS patients. The findings universally show that beginning DMT within three months of clinical presentation will reduce the chance of converting to CDMS.
How to Manage CIS
For those diagnosed with CIS, you may ask what should I expect and what should I do?
The literature shows that one-third of CIS patients will have a benign disease. “Benign” means that after 15 to 20 years, there is minimal or no disability. On the other hand, one-half of CIS patients manifest increased disability over the same period, advancing to secondary progressive MS (SPMS).
For a patient with CIS, close monitoring of the progression of neurologic dysfunction takes precedence. Routine follow-ups with your healthcare provider are essential. In addition, we at BeCare Link have developed an app that helps patients take an active role in their own care. The free BeCare MS Link app puts an easy-to-use tool into the hands of patients to self-monitor their neurologic function and cognition. If you have any questions, please reach out to us at [email protected]. To download BeCare MS Link, go to the Google Play Store here, or the App Store here.