To convert, or not to convert, that is the question: Biomarkers of conversion of Radiologically Isolated Syndrome in Multiple Sclerosis

The prevalence of incidental findings in the central nervous system has increased as a result of technical breakthroughs in neuroimaging techniques and their expanded use as diagnostic tools. It is no longer unusual to detect lesions in brain imaging in otherwise healthy people. Clinicians must therefore be prepared to deal with and counsel these patients. Amongst these incidentalomas is the radiologically isolated syndrome (RIS). It characterizes asymptomatic individuals with incidentally identified white matter lesions highly indicative of multiple sclerosis (MS). Indeed, some RIS patients eventually develop MS, which implies that RIS might be regarded a preclinical stage of MS. Typically, RIS patients present with symptoms such as headache and dizziness that are not particularly attributable to a neurological condition. They are then subjected to brain and/or spine MRI as part of their diagnostic workup, which reveals distinctive radiologic abnormalities. The latter are classified as T2-hyperintence, ovoid, homogeneous brain lesions.

RIS diagnostic criteria have evolved from Barkhof’s initial classification to the updated version proposed by the MAGNIMS study-group, which focuses on demyelinating lesions’ distribution rather than their overall number. Thus, T2-FLAIR hyperintense lesions presence in at least two of the periventricular, cortical/juxta-cortical, spinal-cord, and infratentorial topographies is sufficient to diagnose an RIS patient. It is crucial to emphasize that a single MRI result is insufficient to diagnose RIS; a full clinical history and neurological exam should be performed to rule out any clinical indications of other disorders, most notably MS. Despite being an uncommon condition, the clinical significance of RIS, as well as its implications in the neurological and radiological realms, remain subjects of debate. Indeed, there are multiple ambiguities surrounding this syndrome, including its diagnosis, unclear prognosis, incidence of conversion to MS, and the necessity of treatment initiation at that stage. Up to 45% of RIS patients acquire clinical symptoms within 2.5-5 years after diagnosis. Following this conversion, these individuals were shown to have the same characteristics as traditional MS patients. However, evidence of some RIS patients remaining asymptomatic their whole lives also exist, which raises the necessity to treat the patients: the hazards of therapy outweigh the benefits!

As a result, research is currently focusing on detecting certain signals that can assist clinicians in preventing misdiagnosis, improving medical counseling, and providing appropriate follow-up suggestions and management plans. This research topic will therefore review the clinical aspect of RIS and evaluate existing diagnostic tools and new emerging techniques and their ability to predict the conversion of RIS into a clinically definite MS. We are soliciting articles that cover a broad range of methodologies: clinical, biological and mainly radiological (e.g. pattern-based vs region-based analysis, atrophy and volume measurement using voxel-based morphology and regional volumetry assessment, structural analysis using diffusion tensor imaging, metabolic assessment using MR spectroscopy, central vein sign assessment, etc…) that could differentiate RIS into MS converters from other MS mimickers. The various findings will be covered by either new evidence, case studies or review papers.


Posted on

March 30, 2022