Central vein sign: A putative diagnostic marker for multiple sclerosis

Chaaban, Lara; Safwan, Nancy; Moussa, Hussein; El-Sammak, Sally; Khoury, Samia J.; Hannoun, Salem

doi:10.1111/ane.13553

Cited by 11 publications

(6 citation statements)

References 67 publications

(187 reference statements)

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“…A higher proportion of CVS-positive lesions was found in patients with MS/CIS compared to all the other conditions considered, resulting in high diagnostic performance. High specificity and moderate sensitivity were reached using the previously proposed 40% cutoff . Interestingly, in our cohort a lower cutoff (26%) showed the highest discriminative performance based on the Youden index, confirming the results of a similar previous multicenter study .…”

Section: Discussionsupporting

confidence: 90%

“…The diagnostic performance was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001). Using the previously proposed 40% threshold, 27 the CVS provided sensitivity, specificity, and accuracy of 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. Based on the Youden index, a 26% CVS-positive proportion threshold had the best discriminative performance (sensitivity, specificity, and accuracy: 88.0% [95% CI, 85.3-90.7], 80.9% [95% CI, 76.6-84.9], and 85.3% [95% CI, 83.0-87.6], respectively).…”

Section: Resultsmentioning

confidence: 99%

“…We investigated the influence of the different susceptibility-weighted sequences on CVS diagnostic performance (eMethods in Supplement 1). We assessed the diagnostic performance of the CVS using a range of simplified criteria, alternative to the proportion of CVS-positive lesions, including the “Select-3,” “Pick-6,” and “Select-n*” algorithms . Such criteria have been proposed to expedite the evaluation process and promote the applicability of the CVS in clinical settings (eMethods, eFigures 10-12, and eTables 5-7 in Supplement 1).…”

Section: Methodsmentioning

confidence: 99%

“…We assessed the diagnostic performance of the CVS using a range of simplified criteria, alternative to the proportion of CVS-positive lesions, including the “Select-3,” “Pick-6,” and “Select-n*” algorithms. 27 , 28 , 29 , 30 Such criteria have been proposed to expedite the evaluation process and promote the applicability of the CVS in clinical settings (eMethods, eFigures 10-12, and eTables 5-7 in Supplement 1 ). An estimation of the time required for conducting CL and CVS assessments is reported in the eMethods in Supplement 1 .…”

Section: Methodsmentioning

confidence: 99%

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

Cagol,

Cortese,

Barakovic

et al. 2024

JAMA Neurol

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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 &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 RelevanceThe findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Cagol,

Cortese,

Barakovic

et al. 2024

JAMA Neurol

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“…Indeed, the absence of clear definitions and standard MRI sequences for their detection contribute to the challenges in utilizing these biomarkers. However, highresolution T2*W three-dimensional echoplanar imaging (3D-EPI) or fluid-attenuated inversion recovery (FLAIR*) sequences have been identified as optimal for CVS detection [30,78,79], while phase 3D-EPI, susceptibility weighted imaging (SWI), quantitative susceptibility mapping (QSM), and multi-echo T2* gradient echo (GRE) are recommended for PRS assessment [80]. Nonetheless, these sequences are currently missing from diagnostic MR protocols.…”

Section: Discussionmentioning

confidence: 99%

Central vein sign and paramagnetic rim sign: From radiologically isolated syndrome to multiple sclerosis

Abou Mrad,

Naja,

Khoury

et al. 2023

Euro J of Neurology

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The widespread use of magnetic resonance imaging (MRI) has led to an increase in incidental findings in the central nervous system. Radiologically isolated syndrome (RIS) is a condition where imaging reveals lesions suggestive of demyelinating disease without any clinical episodes consistent with multiple sclerosis (MS). The prognosis for RIS patients is uncertain, with some remaining asymptomatic while others progress to MS. Several risk factors for disease progression have been identified, including male sex, younger age at diagnosis, and spinal cord lesions. This article reviews two promising biomarkers, the central vein sign (CVS) and the paramagnetic rim sign (PRS), and their potential role in the diagnosis and prognosis of MS and RIS. Both CVS and PRS have been shown to be accurate diagnostic markers in MS, with high sensitivity and specificity, and have been useful in distinguishing MS from other disorders. Further research is needed to validate these findings and determine the clinical utility of these biomarkers in routine practice.

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Brain lesion characteristics in Chinese multiple sclerosis patients: A 7‐T MRI cohort study

Su,

Zhang,

Gao

et al. 2024

Ann Clin Transl Neurol

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ObjectivePrevalence, susceptibility genes, and clinical and radiological features may differ across different ethnic groups of multiple sclerosis (MS). We aim to characterize brain lesions in Chinese patients with MS by use of 7‐T MRI.MethodsMS participants were enrolled from the ongoing China National Registry of Neuro‐Inflammatory Diseases (CNRID) cohort. 7‐T MRI of the brain was performed. Each lesion was evaluated according to a standardized procedure. Central vein sign (CVS) and paramagnetic rim lesions were identified. The characteristics of lesions at patient‐level and at lesion‐level from previous 7‐T MRI literature were also summarized.ResultsWe included 120 MS patients. Their mean (SD) age was 34.6 (9.4) years. The female‐to‐male ratio was 1.7:1 and mean disease duration of patients with MS was 5.5 ± 6.1 years. The median EDSS score was 2 (range, 0–8). A total of 8502 lesions were identified with a median lesion count of 45 (IQR, 18–90) (range, 2–370). The median (IQR) percentage for these special locations were as follows: cortical lesions (CLs) 2.7% (0%–5.7%), juxtacortical lesions 16.2% (7.8%–25.7%), periventricular lesions 30.2% (17.2%–38.7%), and infratentorial lesions 5.8% (0.4%–11.9%). CLs occurred in 70 (58%) patients, accounting for only 443 (5%) of the total lesions. Out of the 443 CLs, 309 (69.8%) were leukocortical lesions. CVS appeared in 5392 (63%) lesions from 117 (98%) patients. 1792 (21%) lesions and 104 (87%) patients exhibited a paramagnetic rim.InterpretationOur study elaborated on the lesion features of Chinese patients with MS by use of 7‐T MRI. Lesion burden is heavy in Chinese patients with MS. The median lesion count and proportion of PRL are high. The reported heavy lesion burden calls for ramping up regional and global efforts to care for MS patients. The management and research of Chinese population with MS needs to be further strengthened.

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Central vein sign: A putative diagnostic marker for multiple sclerosis

Cited by 11 publications

References 67 publications

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

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

Central vein sign and paramagnetic rim sign: From radiologically isolated syndrome to multiple sclerosis

Brain lesion characteristics in Chinese multiple sclerosis patients: A 7‐T MRI cohort study

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