Radiologically Isolated Syndrome (RIS) is when a chance scan picks up evidence to suggest MS and here the person was a child with active disease and was treated with natalizumab for 18 years and the development of confirmed MS never materialised.

So does this say that natalizumab is so ace we should give it to people as quick as possible?

ProfK is doing this at the moment with the aim of offering people the option of natalizumab within 14 days of their first notable neurological symptom suggestive of MS. However, ProfK is not treating children in his AttackMS trial. We all should know that natalizumab is a very effective treatment and is this evidence that natalizumab should be offered for RIS. There have been trials with teriflunomide and dimethyl fumarate that inhibited the conversion to MS in trials but that does not fit with the idea of early, high-efficacy treatment. I am aware there was a trial of ocrelizumab but as recruitment was slow, pharma I believe pulled the plug. But what will people do?

You can now diagnose MS at RIS so you could treat RIS but what drug should one use? This person was treated for 18 years but if we look at RIS and ask what proportion develop MS? The answer is not 100%

Etemadifar M, Janghorbani M, Koushki MM, Etemadifar F, Esfahani MF. Conversion from radiologically isolated syndrome to multiple sclerosis. Int J Prev Med. 2014; 5:1379

So, you haven’t experienced symptoms of MS and you could be destined to a lifetime of drug. So maybe this is where an immune reconstitution therapy may be in order such that there is a short term treatment for long term benefit.

I will be interested to know how this pans out.

Ghezzi A, Pozzato M, Annovazzi P, Antozzi C, Erbetta A, Torri Clerici V. Paediatric Radiologically Isolated Syndrome (RIS): A Case with Active Disease 18 Years Later. Neurol Ther. 2026. doi: 10.1007/s40120-026-00954-8.

Introduction: Radiologically isolated syndrome (RIS) is defined by incidental MRI findings suggestive of central nervous system (CNS) demyelination in asymptomatic individuals. While uncommon in adults, RIS is exceptionally rare in the paediatric population. Its management, particularly regarding the timing and potential benefits of high-efficacy disease-modifying therapies (DMT), remains debated.

Case presentation: We describe a 12-year-old girl who underwent an incidental brain MRI during a school visit, revealing multiple white matter lesions. Despite being asymptomatic, the presence of cerebrospinal fluid oligoclonal bands and a high radiological lesion burden, with evidence of dissemination in space and time during follow-up, indicated a high risk of conversion to multiple sclerosis (MS). Rapid radiological worsening and marked inflammatory activity (multiple gadolinium-enhancing lesions in repeated MRI scans) despite corticosteroid treatment prompted initiation of natalizumab in 2009. Over 18 years of continuous therapy, the patient remained clinically asymptomatic, with no new MRI lesions. The patient maintained an excellent quality of life, successfully completing medical school and residency.

Conclusions: In this case of paediatric RIS, early intervention of a high-efficacy DMT prevented clinical conversion to MS, despite aggressive radiological activity in the pre-treatment phase. The patient remained free of clinical and radiological activity over an 18-year follow-up supporting the long-term safety and sustained efficacy of natalizumab, and suggesting that proactive treatment may be beneficial in patients with high-risk RIS.

Source: multiple-sclerosis-research.org