Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis

Karlo Toljan^{1

2}, Lynn Daboul^{3

4}, Praneeta Raza², Melissa L Martin^{5

6}, Quy Cao^{5

6}, Carly M O'Donnell^{5

6}, Paulo Rodrigues⁷, John Derbyshire⁸, Christina J Azevedo⁹, Amit Bar-Or¹⁰, Eduardo Caverzasi^{11

12}, Peter A Calabresi¹³, Bruce Ac Cree¹¹, Leorah Freeman¹⁴, Roland G Henry¹¹, Erin E Longbrake¹⁵, Jiwon Oh¹⁶, Nico Papinutto¹¹, Daniel Pelletier⁹, Rohini D Samudralwar^{10

17}, Matthew K Schindler¹⁰, Elias S Sotirchos¹³, Nancy L Sicotte¹⁸, Andrew J Solomon¹⁹, Russell T Shinohara^{5

6

20}, Daniel S Reich³, Pascal Sati^{3

18}, Daniel Ontaneda²

Affiliations

¹ Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
² Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
³ Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁴ Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA/Department of Neurology, Brigham and Women's Hospital, MA, USA.
⁵ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Penn Statistics in Imaging and Visualization Endeavor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ QMENTA, Boston, MA, USA.
⁸ Functional MRI Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
⁹ Department of Neurology, University of Southern California, Los Angeles, CA, USA.
¹⁰ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Weill Institute for Neurosciences, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
¹² Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
¹³ Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
¹⁴ Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
¹⁵ Department of Neurology, Yale University, New Haven, CT, USA.
¹⁶ Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁷ Department of Neurology, University of Texas Health Science Center, Houston, TX, USA.
¹⁸ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
²⁰ Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

PMID: 39234802
PMCID: PMC11421977
DOI: 10.1177/13524585241271988

Comparative Study

Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis

Karlo Toljan et al. Mult Scler. 2024 Sep.

. 2024 Sep;30(10):1268-1277.

doi: 10.1177/13524585241271988. Epub 2024 Sep 5.

Authors

Affiliations

¹ Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
² Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
³ Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁴ Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA/Department of Neurology, Brigham and Women's Hospital, MA, USA.
⁵ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Penn Statistics in Imaging and Visualization Endeavor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ QMENTA, Boston, MA, USA.
⁸ Functional MRI Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
⁹ Department of Neurology, University of Southern California, Los Angeles, CA, USA.
¹⁰ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Weill Institute for Neurosciences, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
¹² Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
¹³ Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
¹⁴ Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
¹⁵ Department of Neurology, Yale University, New Haven, CT, USA.
¹⁶ Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁷ Department of Neurology, University of Texas Health Science Center, Houston, TX, USA.
¹⁸ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁹ Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
²⁰ Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

PMID: 39234802
PMCID: PMC11421977
DOI: 10.1177/13524585241271988

Abstract

Background: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) are a diagnostic biomarker in multiple sclerosis (MS). The central vein sign (CVS) is an imaging biomarker for MS that may improve diagnostic accuracy.

Objectives: The objective of the study is to examine the diagnostic performance of simplified CVS methods in comparison to OCB in participants with clinical or radiological suspicion for MS.

Methods: Participants from the CentrAl Vein Sign in MS (CAVS-MS) pilot study with CSF testing were included. Select-3 and Select-6 (counting up to three or six CVS+ lesions per scan) were rated on post-gadolinium FLAIR* images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for Select-3, Select-6, OCB, and combinations thereof were calculated for MS diagnosis at baseline and at 12 months.

Results: Of 53 participants, 25 were OCB+. At baseline, sensitivity for MS diagnosis was 0.75 for OCB, 0.83 for Select-3, and 0.71 for Select-6. Specificity for MS diagnosis was 0.76 for OCB, 0.48 for Select-3, and 0.86 for Select-6. At 12 months, PPV for MS diagnosis was 0.95 for Select-6 and 1.00 for Select-6 with OCB+ status.

Discussion: Results suggest similar diagnostic performance of simplified CVS methods and OCB. Ongoing studies will refine whether CVS could be used in replacement or in conjunction with OCB.

Keywords: biomarker; central vein sign; diagnostic imaging; multiple sclerosis; oligoclonal bands.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Karlo Toljan: Training grant: National MS Society (FP-2207-39855).Lynn Daboul: Research support: NIH Medical Research Scholars Program.Praneeta Raza: Nothing to disclose.Melissa L. Martin: Nothing to disclose.Quy Cao: Nothing to disclose.Carly M. O’Donnell: Nothing to disclose.Paulo Rodrigues: Employed by and holds options of QMENTA.John Derbyshire: Nothing to disclose.Christina J. Azevedo: Research support: National Multiple Sclerosis Society, National Institutes of Health. Consulting: Genentech, EMD Serono, Alexion Pharmaceuticals, Sanofi Genzyme, Horizon Therapeutics.Amit Bar-Or: Consulting: Accure, Atara Biotherapeutics, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Gossamer, Janssen, AstraZeneca, EMD Serono, Novartis, Genentech, Sanofi. Research support: Biogen, Genentech, EMD Serono, Novartis.Eduardo Caverzasi: Nothing to disclose.Peter A Calabresi: Research support: Genentech. Advisory board: Lilly, Novartis, Idorsia, and Project Efflux.Bruce A. C. Cree: Consulting: Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Kyverna, Neuron23, Novartis, Sanofi, and TG Therapeutics; research support from Genentech.Leorah Freeman: Advisory board: Genentech, Novartis, Celgene. Consulting: EMD Serono, Celgene, Biogen. Program sponsorship: Biogen, EMD Serono.Roland G. Henry: Consulting: Neurona, Roche, Novartis, Sanofi, QIA, Celgene/BMS, Atara, Medday, Boston Pharma. Research support: Roche, Atara.Erin E Longbrake: Consulting: Genentech, Sanofi, Alexion, Biogen, EMD Serono, Bristol Myers Squibb.Jiwon Oh: Research support: Biogen, Roche, EMD Serono. Consulting: EMD Serono, Sanofi, Biogen, Roche, Celgene, Novartis.Nico Papinutto: Research support: Race to Erase MS Foundation.Daniel Pelletier: Consulting: Sanofi, Roche, Novartis.Rohini D. Samudralwar: Advisory board: Biogen, EMD Serono, Sanofi. Consulting: EMD Serono, Biogen.Matthew K. Schindler: Nothing to disclose.Elias S. Sotirchos: Consulting for Alexion, Viela Bio, Horizon Therapeutics, Genentech, Ad Scientiam. Honoraria: Alexion, Viela Bio, Biogen.Nancy L. Sicotte: Research support: NIH, National MS Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Biogen.Andrew J. Solomon: Advisory board: Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics. Consulting: Octave Bioscience. Non-promotional speaking: EMD Serono. Research support: Bristol Myers Squibb, Sanofi, Biogen, Novartis, Janssen, Genentech. Trainee funding: Biogen.Russell T. Shinohara: Consulting: Octave Bioscience. Research support: NIH, National MS Society.Daniel S. Reich: Supported by Intramural Research Program of NINDS. Research support: Abata, Sanofi.Pascal Sati: Research support: NIH, National MS Society, Erwin Rautenberg Foundation.Daniel Ontaneda: Research support: NIH, National MS Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Bristol Myers Squibb, Genentech, Sanofi, Novartis. Consulting: Biogen, Bristol Myers Squibb, Genentech, Sanofi, Janssen, Novartis, Pipeline Therapeutics, and Merck.

References

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Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis

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Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis

Authors

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Abstract

Conflict of interest statement

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