INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS characterized by white matter lesions and diffuse neurodegeneration leading to visual, sensory, motor and cognitive dysfunction. Radiologically isolated syndrome (RIS) refers to asymptomatic individuals with MRI findings suggestive of MS. Some RIS individuals may fulfill the recently revised diagnostic criteria for MS based on cerebrospinal fluid findings but the extent of underlying damage and prognosis are largely unknown.

AIM(S): This study aimed to examine cognitive performance and brain structure volume in RIS subjects, patients with clinically definite MS, and healthy controls (HC).

METHOD(S): 29 RIS subjects, 27 MS patients and 22 HC underwent cognitive testing (SDMT, CVLT-II, BVMT-R, Digit Span, Stroop task) and 3T MRI. Cognitive impairment was defined as ≥2 scores below 1,5 SD. Brain volumes (whole brain, thalamus, hippocampus, cortical thickness) were assessed using FreeSurfer.

RESULTS: MS patients had lower normalized SDMT (-0,519 ± 0,778) when compared with RIS (-0,172 ± 0,827) and HC (0,265 ± 1,033, p = ,008). No significant group differences were found in other cognitive domains. Cognitive impairment was identified in 4/29 RIS and 4/27 MS subjects. MS patients had lower thalamic volume (mean 8,074 ± 0,829, p < ,05), when compared with RIS (8,552 ± 0,736) and HC (8,864 ± 0,710). In regression analyses, mean cortical thickness (p = ,003) and thalamic volume (p =,015) predicted SDMT scores while thalamic volume predicted BVMT performance (p = ,009).

CONCLUSIONS: As reported previously, MS patients showed impairment in information processing speed associated with lower thalamus volume. While RIS subjects on a group level did not differ significantly from HC in cognitive function or brain structure volume, 14% fulfilled the criteria for cognitive impairment, indicating heterogeneity. Longitudinal analyses will determine the predictive value of cognitive and volumetric measures for conversion to clinically definite MS.

FINANCIAL SUPPORT: The study is funded and conducted as part of the research component of the National Science Centre 2021/42/E/NZ5/00213. “Predicting prognosis in asymptomatic individuals with multiple sclerosis-like brain lesions using cognitive tests and advanced magnetic resonance imaging techniques.”