Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis
Authors: Alessandro Cagol, Rosa Cortese, Muhamed Barakovic, Sabine Schaedelin, Esther Ruberte, Martina Absinta, Frederik Barkhof, Massimiliano Calabrese, Marco Castellaro, Olga Ciccarelli, Sirio Cocozza, Nicola De Stefano, Christian Enzinger, Massimo Filippi, Maciej Jurynczyk, Pietro Maggi, Nima Mahmoudi, Silvia Messina, Xavier Montalban, Jacqueline Palace, Giuseppe Pontillo, Anne-Katrin Pröbstel, Maria A. Rocca, Stefan Ropele, Àlex Rovira, Menno M. Schoonheim, Piotr Sowa, Eva Strijbis, Mike P. Wattjes, Maria Pia Sormani, Ludwig Kappos, Cristina Granziera, Jaume Sastre-Garriga, Claudio Gasperini, Hugo Vrenken, Tarek Yousry
Journal: JAMA Neurology (2023)

Importance Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. Objective To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). Design, Setting, and Participants This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants’ diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). Exposures MS/CIS vs non-MS conditions. Main Outcomes and Measures Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. Results The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P &amp;amp;lt; .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. Conclusions and Relevance The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.