Radiologically isolated syndrome (RIS) refers to an incidental finding in magnetic resonance imaging (MRI) where lesions typical of multiple sclerosis (MS) are found, even though the MRI was not performed under clinical suspicion of MS, but for a completely different reason, e.g. for the clarification of headaches. And although in such a case MS-typical lesions were found, the patient’s medical history provides no indication of symptoms of MS. – Here now an update on radiologically isolated syndrome.
An abnormal MRI finding is initially not pathological – because disease is defined by a disruption of normal physical or psychological functions that lead to a negative influence on the performance and well-being of an individual. Therefore, I have also been relatively reserved in the past about deriving consequences from such an “incidental finding” (see also DocBlog from February 8, 2018). The current guidelines for diagnosis and therapy of Multiple Sclerosis in the revised version of November 2023 also do not recommend therapeutic intervention at the detection of RIS and suggest an initial wait-and-see approach.
Start MS therapy after RIS?
However, I am currently unsure whether this is really still a sensible approach.
But first to the facts: Based on the observation of a multicentric RIS cohort with 451 individuals, whose MRI showed MS-typical lesions, we know that after 10 years 51% of the examined people develop a first clinical event indicating a demyelinating disease (Lebrun-Frenay C et al. Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event. Ann Neurol. 2020 Aug;88(2):407-417). As risk factors for the occurrence of clinical symptoms were identified:
- a young age (< 37 years),
- evidence of oligoclonal bands in the cerebrospinal fluid,
- the presence of infratentorial and spinal lesions in MRI and
- the detection of contrast-enhancing lesions in MRI
Especially when several risk factors are present at the same time, the risk of developing clinical symptoms in the further course increased to almost 90% (Lebrun-Frénay C et al. Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome. JAMA Netw Open. 2021 Oct 1;4(10):e2128271).
In addition, two clinical studies have already been able to show that it can be advantageous to treat individuals with RIS with immunotherapy. In the TERIS study with 89 RIS patients, Teriflunomide (e.g., Aubagio®) reduced the risk of developing MS by 72% (Lebrun-Frénay C et al. Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1080–1088). And the use of Dimethyl Fumarate (e.g., Tecfidera®) over 96 weeks led to a significant reduction of new and/or enlarging MRI lesions compared to placebo. In addition, treatment with Dimethyl Fumarate compared to placebo resulted in a risk reduction of over 80% in preventing a first clinical event (Okuda DT et al. Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome. Ann Neurol. 2023; 93(3):604–614).
RIS = early MS?
Given that we currently do not have sufficiently potent drugs to treat progressive MS, early anti-inflammatory treatment of MS is a generally accepted measure to prevent or at least delay the progression of pathology. Therefore, we should perhaps see the detection of RIS as an opportunity for those affected to initiate treatment as early as possible. Most experts have little doubt that RIS is an early manifestation of MS. Of course, it must also be mentioned in this context that no MS drug has yet been approved for the treatment of RIS (despite the positive studies). Therefore, a broad consensus and support through the adjustment of guidelines is certainly needed here.
Personally, I am convinced that the development will go towards identifying and treating MS earlier – i.e., already in the prodromal stage, probably with the help of biochemical methods that are possibly even more sensitive than MRI. Until then, however, I believe that we should already try to respond adequately to the information that the MRI offers, including RIS.
