Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis: A 3-Year Longitudinal Study

Omar Al-Louzi, Vijay Letchuman, Sargis Manukyan, Erin S Beck, Snehashis Roy, Joan Ohayon, Dzung L Pham, Irene Cortese, Pascal Sati, Daniel S Reich, Omar Al-Louzi, Vijay Letchuman, Sargis Manukyan, Erin S Beck, Snehashis Roy, Joan Ohayon, Dzung L Pham, Irene Cortese, Pascal Sati, Daniel S Reich

Abstract

Background and objectives: The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS- lesion development.

Methods: In this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review.

Results: A total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1-Q3: 0.7-6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS-, and 20 (32%) both CVS+ and CVS- lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3-0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1-1.9) were associated with increased likelihood of new CVS+ lesion development.

Discussion: In a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status.

Trial registration information: Clinical trial registration number NCT00001248.

Classification of evidence: This study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Study Eligibility Criteria and Patient…
Figure 1. Study Eligibility Criteria and Patient Inclusion Flowchart
CVS = central vein sign; CIS = clinically isolated syndrome; HC = healthy control; MS = multiple sclerosis; NAIMS = North American Imaging in Multiple Sclerosis Cooperative.
Figure 2. Longitudinal Evolution of Newly Developing…
Figure 2. Longitudinal Evolution of Newly Developing CVS+ and CVS− Lesions in Multiple Sclerosis
A and B depict examples of new CVS− and CVS+ lesion development, respectively. Red insets show magnified views of the lesion on FLAIR*, in which central veins appear as hypointense dots or lines, and green insets depict magnified views of the lesion on longitudinal subtraction imaging. C and D show examples of gadolinium-enhancing lesions with poor initial venular visibility, despite the vein being present on scans obtained before lesion formation. Venular visibility gradually improves following resolution of enhancement and intra-/perilesional edema (blue arrowheads). Blue insets show magnified views of corresponding postgadolinium T1-weighted images. CVS = central vein sign; FLAIR = fluid-attenuated inversion recovery.
Figure 3. New CVS+ Lesion Development in…
Figure 3. New CVS+ Lesion Development in Multiple Sclerosis Is Associated With Younger Age and Higher Baseline CVS Percentage
Relationship between fitted probabilities of new CVS+ lesion development generated using multivariate logistic regression, adjusted for age, sex, race, T2*-weighted image gadolinium status, follow-up duration, and baseline CVS+ percentage (A), as well as age at baseline MRI (B). The dimension of each circle is proportional to the duration of MRI follow-up in years. Dashed lines depict a moving average of the probabilities across a span of 10% (A) or 10 years (B). CVS = central vein sign.

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