To assess relationships between cognitive impairment and the central vein sign, paramagnetic rim sign, and brain atrophy in radiologically isloated syndrome

Radiologically isolated syndrome(RIS) describes asymptomatic individuals with incidental MRI abnormalities highly suggestive of multiple sclerosis(MS). Using susceptibility-weighted imaging, we previously showed that a significant proportion of white matter lesions(WML) in RIS have visible CVS and demonstrate an increase in magnetic susceptibility along the lesion rim(PRS), which may represent chronic, smoldering inflammation.  

27 RIS subjects underwent 3.0T-MRI and cognitive assessment using the minimal assessment of cognitive function in MS(MACFIMS)battery. The CVS and PRS were assessed in WMLs on T2*-magnitude and phase images. Brain segmentation was performed with Multi-Atlas CRUISE to assess brain atrophy. Spearman’s coefficient and multivariable linear regression evaluated relationships between CI and MRI measures.

37%of RIS had global CI and 93%had a proportion of CVS+WML that was>40%. 58%of RIS demonstrated PRS+WML, and the mean proportion of PRS+WML was 12%. There were significant correlations between individual cognitive tests and proportions of CVS+WML and PRS+WML, with the strongest correlations observed with the California Verbal Learning Test-II(CVLT-II) and CVS+WML(ρ=-0.54,p<0.01) and PRS+WML(ρ=-0.44,p=0.02). When relationships between CI, CVS,and PRS were assessed in multivariable models controlling for brain volume:CVS+WML(p=0.02) and PRS+WML(p=0.05) demonstrated relationships with the CVLT-II(p=0.02;p=0.05, respectively) and the Paced Auditory Serial Addition Test(p<0.01;p=0.02,respectively).

CI is common in RIS and demonstrates significant relationships with CVS+WML and PRS+WML,independent of brain atrophy. The CVS and PRS are thought to reflect perivenular demyelination and chronic inflammation, respectively. These findings suggest that perivenular demyelination and chronic, smoldering inflammation in WML are relevant to CI in RIS, and raise the possibility that CI may be useful to identify those at higher risk of conversion to MS. Prospective follow-up of this cohort will give insight into the predictive value of CI, CVS, and PRS in the clinical management of RIS.