ReviewActa neurologica Belgica2026
The multi-dimensional spectrum of radiologically isolated syndrome: a systematic review of cognitive and psychosocial evidence.
Review in Acta neurologica Belgica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
3 authors.
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Abstract
backgroundRadiologically isolated syndrome (RIS) is traditionally viewed as a preclinical state. However, emerging evidence suggests it represents an active subclinical stage of the multiple sclerosis (MS) spectrum. This systematic review integrates evidence across cognitive and psychosocial domains, along with secondary neuroimaging and biomarker findings, to explore the clinical conceptualization of RIS.
methodsFollowing PRISMA guidelines, a systematic search was conducted across PubMed, Cochrane Library, and ClinicalTrials.gov for studies published between January 2010 and May 2026. Eligible studies focused on cognitive performance, psychosocial measures, and biomarkers in RIS. Quality was evaluated using the ROBINS-E tool.
resultsThirteen studies met the eligibility criteria and were included in the final synthesis. The evidence reveals that a substantial proportion of individuals with RIS exhibit cognitive impairment, with information processing speed and executive functions being the most affected domains. Psychosocial burdens, including clinical depression and pathological fatigue, are prevalent and significantly impact quality of life. Furthermore, advanced neuroimaging and molecular biomarkers confirm ongoing neurodegeneration and inflammatory activity, characterized by cortical thinning, thalamic atrophy, and elevated neurofilament levels. Despite these subclinical changes, evidence suggests that baseline cognitive performance does not consistently predict short-term clinical conversion to symptomatic MS.
conclusionsCurrent evidence suggests that at least a subset of individuals with RIS may represent an active subclinical phase of MS involving measurable neuroaxonal damage and psychosocial deterioration. However, given the limited number of studies and high risk of bias, definitive conclusions remain challenging. These findings highlight the potential need for a paradigm shift in clinical management, where incorporating targeted neuropsychological assessments and sensitive biomarkers could aid in accurate disease staging and optimized risk stratification.
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