Even prior to the introduction of RIS criteria, longitudinal clinical data from individuals with incidentally identified T2 lesions suggestive of multiple sclerosis (MS) were described. Healthy individuals who do not exhibit signs of neurological dysfunction commonly have brain MRI studies performed for a reason other than an evaluation for MS that reveal unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack symptomatology suggestive of MS and fulfill formal criteria for the radiologically isolated syndrome (RIS), a recently described MS subtype that expands upon the phenotype of at-risk individuals for future demyelinating events. A formal description of RIS was first introduced in 2009 by Okuda et al., to define this relevant cohort of individuals who are at risk for future demyelinating events.
In European or North American observational studies, the authors have found that up to 30-45% of patients presenting with a RIS will present clinical progression. The presence of asymptomatic lesions in the cervical cord provides an increased risk of progression, either to a relapsing or to progressive MS.
The consortium studying epidemiology of RIS worldwide (RISC) presented their first retrospective cohort. The 5-year observed conversion rate to the first clinical event was 34%. Of converters within this time period, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age, sex (male), and lesions within the cervical or thoracic spinal cord were identified as significant predictors for the development of a first clinical event. In the 10-year update, more than half of the RIS have converted with 4 risk factors at baseline which are young age, CSF positivity, Spinal cord, and infratentorial lesions.
Despite advancements in the characterization of RIS subjects and in our understanding of risk factors for initial symptom development, the natural course of such cases and risk-profiles for a seminal neurological event, from prospectively acquired data, remain unclear. Prospective studies are mandatory to increase our knowledge about these asymptomatic patients. Many experts groups in the USA, Europe, and South America have proposed guidelines to follow the RIS subjects. The recommendation is not to treat off label these subjects as 2 phases 3 studies are ongoing in the USA and Europe with dimethylfumarate and teriflunomide.