Cognitive Impairment, Central Vein Sign, and Paramagnetic Rim Lesions in Radiologically Isolated Syndrome

 

TAKE-HOME MESSAGE

  • The authors of this study examined the association between cognitive impairment and paramagnetic rim lesions in 27 patients with radiologically isolated syndrome. Overall, 9 patients had global cognitive impairment. Paramagnetic rim lesions (activated microglia and macrophages around demyelinating lesions) were associated with decreased performance in both verbal memory (P = .04) and processing speed (P = .03). Lesions with central vein signs were associated with decreased performance in verbal memory (P = .03).

  • This was a small preliminary study demonstrating that some patients with radiologically isolated syndrome have global cognitive impairment despite not having overt neurologic deficits. If replicated, the results could indicate that paramagnetic rim lesions could be a marker of cognitive impairment in these patients.
–  Kyle Binder, MD

 Multiple Sclerosis

Around 20% to 30% of patients presenting with radiologically isolated syndrome (RIS) experience cognitive impairment (CI),1 with a profile similar to that observed in multiple sclerosis (MS).1,2 Emerging MRI measures in MS, such as paramagnetic rim lesions (PRLs), a marker of chronic, smoldering inflammation, and the central vein sign (CVS), a marker of perivenular demyelination, have been identified in RIS.3,4 The aim of this study was to determine the association between CI and presence of the CVS and PRLs in patients with RIS.

In this cross-sectional study, 9 of 27 individuals (33%) with RIS showed CI, affecting processing speed and memory, in particular. Overall, 93% presented positive CVS in over 40% of white matter lesions (WMLs), and 63% presented PRLs. Linear regression analysis between cognitive tests and radiological metrics revealed that the proportion of PRLs predicted performance on verbal memory, CVLT (β = −0.040; P = .04), and processing speed, PASSAT-3 (β = −0.039; P = .03), SDMT (β = −0.031; P = .04). CVS + WMLs, on the other hand, was predictive of poor performance on verbal memory (β = −0.024; P = .04).

Based on their results, the authors concluded that CVS and PRLs are sensitive markers of subtle cognitive deterioration in RIS. They found no correlation between CI and brain atrophy, whereas others found reduced cortical volume and high T1 hypointense lesion volume associated with CI in RIS.2 In this article, PRLs were the strongest predictor of cognitive impairment. Interestingly, people with MS with more PRLs reached worse cognitive disability at a younger age.5 These observations raise the possibility that PRLs may play a role in neurological mechanisms underlying early cognitive impairment. Longitudinal follow-up of this and other cohorts is relevant, as it is critical in clinical practice to determine the prognostic role of early CI and these imaging metrics in order to identify patients at higher risk of conversion to MS.

References

  1. Lebrun C, Blanc F, Brassat D, et al. Cognitive function in radiologically isolated syndrome. Mult Scler. 2010;16(8):919–925. https://journals.sagepub.com/doi/10.1177/1352458510375707
  2. Amato MP, Hakiki B, Goretti B, et al. Association of MRI metrics and cognitive impairment in radiologically isolated syndromes. Neurology. 2012;78(5):309-314. https://n.neurology.org/content/78/5/309.long
  3. Suthiphosuwan S, Sati P, Guenette M, et al. The Central Vein Sign in Radiologically Isolated Syndrome. AJNR Am J Neuroradiol. 2019;40(5):776-783. http://www.ajnr.org/content/40/5/776.long
  4. Suthiphosuwan S, Sati P, Absinta M, et al. Paramagnetic Rim Sign in Radiologically Isolated Syndrome. JAMA Neurol. 2020;77(5):653-655. https://jamanetwork.com/journals/jamaneurology/fullarticle/2762513
  5. Absinta M, Sati P, Masuzzo F, et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 2019;76(12):1474-1483. https://jamanetwork.com/journals/jamaneurology/fullarticle/2747565

OBJECTIVE

The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS).

METHODS

Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures.

RESULTS

Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory(β =-0.024, p = 0.03) while PRL predicted performance on verbal memory (β = -0.040, p = 0.04) and processing speed (β = -0.039, p = 0.03).

CONCLUSIONS

CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.

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