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March 2022; 9 (2) ArticleOpen Access

Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis

A 3-Year Longitudinal Study

View ORCID ProfileOmar Al-Louzi, View ORCID ProfileVijay Letchuman, Sargis Manukyan, View ORCID ProfileErin S. Beck, View ORCID ProfileSnehashis Roy, Joan Ohayon, View ORCID ProfileDzung L. Pham, Irene Cortese, View ORCID ProfilePascal Sati, View ORCID ProfileDaniel S. Reich
First published January 13, 2022, DOI: https://doi.org/10.1212/NXI.0000000000001120
Omar Al-Louzi
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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  • For correspondence: oallouzi1@gmail.com
Vijay Letchuman
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Sargis Manukyan
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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  • For correspondence: sargis.manukyan@nih.gov
Erin S. Beck
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Snehashis Roy
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Joan Ohayon
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Dzung L. Pham
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Irene Cortese
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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  • For correspondence: corteseir@ninds.nih.gov
Pascal Sati
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Daniel S. Reich
From the Translational Neuroradiology Section (O.A.-L., V.L., S.M., E.S.B., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Department of Neurology (O.A.-L., P.S.), Cedars-Sinai Medical Center, Los Angeles, CA; Section on Neural Function (S.R.), National Institute of Mental Health, NIH, Bethesda, MD; Neuroimmunology Clinic (J.O., I.C.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Center for Neuroscience and Regenerative Medicine (D.L.P.), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
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Citation
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
Neurol Neuroimmunol Neuroinflamm Mar 2022, 9 (2) e1120; DOI: 10.1212/NXI.0000000000001120

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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.

Glossary

CIS=
clinically isolated syndrome;
CVS=
central vein sign;
DMT=
disease-modifying therapy;
FLAIR=
fluid-attenuated inversion recovery;
Gd+=
gadolinium enhancing;
HC=
healthy control;
ICBM=
International Consortium for Brain Mapping;
MNI=
Montreal Neurologic Institute;
MS=
multiple sclerosis;
NAIMS=
North American Imaging in Multiple Sclerosis;
PPMS=
primary progressive MS;
RRMS=
relapsing-remitting MS;
SPMS=
secondary progressive MS

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • ↵* O. Al-Louzi and V. Letchuman contributed equally to this work as co–first authors.

  • The Article Processing Charge was funded by the NIH.

  • Class of Evidence: NPub.org/coe

  • Received August 9, 2021.
  • Accepted in final form October 22, 2021.
  • Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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