Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis

Abstract

ImportanceMultiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice.ObjectiveTo 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 ParticipantsThis 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).ExposuresMS/CIS vs non-MS conditions.Main Outcomes and MeasuresArea 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.ResultsThe 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 < .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 RelevanceThe findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis

“…As in previous studies, 8 , 40 , 42 we found CL in the majority of MS cases and only rarely in non-MS cases. When compared with the proportion of CVS-positive lesions, the presence of a single CL provided high specificity but only moderate sensitivity for MS diagnosis.…”

“…As expected, 7 , 9 , 39 , 40 a higher proportion of CVS-positive lesions was found in patients with MS compared with non-MS, resulting in high diagnostic sensitivity and specificity with an optimal CVS-positive lesion frequency cutoff of 41%, which is similar to the previously proposed “40% rule”. 9 , 22 , 23 ⁠ However, the exceptional CVS diagnostic performance and the specific CVS-positive lesion cutoff reported in our study is likely due to the adoption of the same optimized submillimetric 3D T2*-EPI sequence in all participating centers, 14 , 15 with minimal parameter adjustments and centralized postprocessing analysis.…”

“…Recent findings suggest that the adoption of others imaging techniques (i.e., 2D SWI) for the CVS assessment is likely to result in a lower diagnostic performance. 39 - 41 …”

Advanced MRI Techniques: Diagnosis and Follow-Up of Multiple Sclerosis

“…A cut-off of 40% CVS positive lesions of the total amount of white matter lesions has been proposed as a biomarker able to discriminate between MS and non-MS conditions [ 63 ]. In a recent cross-sectional study [ 64 ] involving 1051 participants with variable inflammatory and non-inflammatory disorders, the adherence to the 40% CVS rule showed superior performance compared to the contribution of infratentorial, juxtacortical, and periventricular lesions in aiding the diagnosis of MS [ 64 ]. Other studies, instead, such as Maggi et al, used the 50% CVS cut-off to distinguish MS from vasculopathies [ 65 ].…”

“…Other studies, instead, such as Maggi et al, used the 50% CVS cut-off to distinguish MS from vasculopathies [ 65 ]. Consequently, CVS is highly promising in effectively distinguishing MS from other conditions associated with nonspecific white matter lesions [ 64 , 65 ].…”