You are ordering an MRT to check on your patient’s migraine. But what if you spotted something different – something that could lead to MS? Read here, why simply informing your patient is not always the answer.
“We are treating patients, not diagnostic results” is a popular piece of wisdom that experienced doctors often give to medical students, interns and residents during teaching. In the case of Radiologically Isolated Syndrome, this might not be completely true anymore, since two studies showed the efficacies of treating patients with MRI abnormalities in the absence of clinical symptoms. Radiologically Isolated Syndrome or RIS describes MRI-abnormalities that look like Multiple Sclerosis (MS) but that are not associated with typical symptoms of MS. Since doctors like to order head-MRIs more and more frequently for various symptoms, they get abnormal findings more and more often (“He who seeks finds”).
For example, in the case of migraine, a head-MRI is supposed to show or exclude structural changes that could explain the headache-attacks. If such an MRI reveals changes in the white matter as an incidental finding that are typical of multiple sclerosis, doctor and patient face a dilemma. Although the doctor can tell the patient, that he has Radiologically Isolated Syndrome, but the therapeutic consequences of this diagnosis have been unclear so far.
In MS, the structural changes in the brain and spine might precede clinical symptoms for several years in a subset of patients. However, not every patient whose brain looks like MS develops clinical MS during their lifetime. So, treating RIS like it is MS would mean giving livelong medications to patients that never would have developed any symptoms. This could cause harm because of side effects, even though most patients tolerate disease-modifying treatments (DMTs) for MS well.
Ignoring the MRI-changes might not be the best idea either, since a large cohort study found that about half of RIS-patients do develop clinically manifest MS in the ten years following diagnosis of RIS. It would obviously be a huge benefit for an individual patient, if we could prevent or at least delay the conversion from RIS to MS. Two studies on RIS patients from this year have shown that this goal has come closer and is in fact achievable.
The first of the two studies treated patients with incidental MRI-findings that were suggestive of Multiple Sclerosis with Dimethyl Fumarate (DMF). The investigators enrolled 87 RIS-patients from across twelve centers in the USA and randomly assigned them to receive either DMF 240 mg twice daily or placebo. The primary endpoint of the study was time to onset of clinical symptoms attributable to Multiple Sclerosis during the 96 weeks of follow-up. In the placebo group, 33 % developed neurological symptoms compared to only 7 % in the DMF-group. This translates to a risk reduction of 80 % for those treated with dimethyl fumarate.
This large treatment effect is somewhat relativized by a large confidence interval, which in turn is due to the rather small number of study participants. In addition, DMF-treated participants developed significantly less new lesions on the follow-up MRI. The rate of moderate side effects was higher in the DMF-treated group, but there was no difference in the rate of severe adverse reactions. Limitations to the study were the small number of participants and a discontinuation rate of above 30 % for both the DMF and placebo group.
The second study investigated the efficacy of teriflunomide in preventing conversion from RIS to MS. Investigators enrolled 89 RIS-patients from different centers in France, Switzerland and Turkey and randomly assigned them to receive either 14 mg teriflunomide daily or placebo. The primary endpoint was again time to onset of neurological symptoms attributable to MS. In the placebo group, 44 % developed neurological symptoms compared to only 18 % in the teriflunomide group. This translated to a risk reduction of 60 %. The number of new lesions in the follow-up MRI was numerically lower in the treatment group but this difference did not reach statistical significance. Limitations were again the small number of participants. The discontinuation rate was lower than in the DMF study, with 20 % in both the placebo and treatment group.
Taken together, the two studies demonstrated that two different MS-drugs are effective in preventing the development of clinically manifest Multiple Sclerosis in asymptomatic patients with MRI abnormalities suggestive of MS (Radiologically Isolated Syndrome). The studies were very similar in size and design but differed regarding the drugs they used and the populations that they studied.
The results support the hypothesis that early intervention in RIS may improve clinical outcomes. The decision to start a medication should always be made individually and considering risk factors as well as possible side effects of the respective drugs. Sometimes, it might be justified to treat an asymptomatic patient because of suggestive imaging abnormalities after all.
Image Source: LinkedIn Sales Solutions, Unsplash
