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Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of
Serena Borrelli1, Maria Sofia Martire1, Anna Stölting1
1From the Neuroinflammation Imaging Lab (NIL) (S.B., A.S., C.V.B., F.G., P.M.), Institute of NeuroScience, Université catholique de Louvain; Department of Neurology (S.B., S.E.), Hôpital Erasme, Hôpital Universitaire de Bruxelles; Department of Neurology (S.B.), Centre Hospitalier Universitaire Brugmann, Université Libre de Brussels, Belgium; Neurology Unit (M.S.M., V.M., M.F.), IRCCS San Raffaele Hospital, Milan, Italy; ICTEAM Institute (C.V.B.), Université catholique de Louvain, Louvain-la-Neuve, Belgium; Vita-Salute San Raffaele University (E.P., M.F., M.A.); Translational Neuropathology Unit (E.P., M.A.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Plateforme technologique de Support en Méthodologie et Calcul Statistique (C.B.); Department of Internal Medicine and Infectious Diseases (H.Y., L.P.), Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium; Section of Infections of the Nervous System (B.S.); Viral Immunology Section (S.J.), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD; Neurology Service (R.A.D.P., P.M.), Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland; Department of Neurology (V.V.P., P.M.), Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium; Neuroimaging Research Unit (M.F.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Translational Neuroradiology Section (D.S.R.), National Institute of Neurological Disorders and Stroke (NINDS), National In-stitutes of Health (NIH); and Department of Neurology (M.A.), Johns Hopkins University School of Medicine, Baltimore, MD.
Background And Objectives:
The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes.
Methods:
In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes.
Results:
The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL.
Discussion:
The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.
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