Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event

Ann Neurol. 2020 Aug;88(2):407-417. doi: 10.1002/ana.25799. Epub 2020 Jun 29.


Objective: We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10-year, multinational, retrospectively identified RIS dataset.

Methods: RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models.

Results: Additional follow-up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11-74 years), with a median clinical follow-up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium-enhanced lesions during follow-up was also associated with the risk of a seminal event. The reason for MRI and gadolinium-enhancing lesions at baseline did not influence the risk of a subsequent clinical event.

Interpretation: Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407-417.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Demyelinating Diseases / diagnostic imaging*
  • Demyelinating Diseases / physiopathology
  • Disease Progression*
  • Female
  • Humans
  • Magnetic Resonance Imaging / trends*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / physiopathology
  • Risk Factors
  • Time Factors
  • Young Adult