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Key References
Key References
The latest diagnostic criteria for MS includes the CVS both to support typical and atypical presentations.
The Select 6 criteria is advocated.
113 participants requiring an LP to meet the 2017 McDonald diagnostic criteria were enrolled (80 diagnosed with MS) - prospective multi-centre diagnostic superiority study.
T2*-weighted sequence used to assess CVS.
These were compared with OCBs, using the clinical diagnosis at 18 months as the reference standard.
No significant difference in diagnostic sensitivity was detected between 40% CVS threshold (90% [CI 81%–96%]) and OCB testing (84% [CI 74%–91%]) (p = 0.332).
The rule of 6 had a sensitivity of 91% (CI 83%–96%).
Side effects were reported by 75% following LP compared with 9% following MRI. All participants preferred their MRI scan over their LP.
Analysed participants from the CentrAl Vein Sign in MS (CAVS-MS) pilot study with CSF testing (53 participants, 25 OCB+ve).
Select-3 and Select-6 were rated on post-gadolinium FLAIR* images.
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.
Participants evaluated from ongoing observational studies and neuroimaging research databases. CVS was detected on 3T T2*-weighted or susceptibility-weighted imaging.
4447 lesions were analysed in a total of 487 patients:
690 lesions in 98 participants with CIS
2815 lesions in 225 participants with RRMS
54 lesions in 13 participants with NMOSD
54 lesions in 14 participants with SLE
121 lesions in 29 participants with migraine or cluster headache
240 lesions in 20 participants with diabetes
473 lesions in 88 participants with other types of small-vessel disease
The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold.
The 3 central vein sign lesion criteria had a sensitivity of 61.9% and specificity of 89.0%.
Sensitivity was higher when using an optimised T2*-weighted sequence.
This prospective pilot study recruited individuals with symptoms unusual for MS but with brain MRI consistent with the disease, and those with a typical clinical presentation of MS whose MRI did not suggest MS.
Calculated the proportion of lesions with central veins for each patient and compared with the eventual clinical diagnoses.
38 patients were scanned with 3T T2*, 35 of whom had received a clinical diagnosis.
Median percentage of lesions with central veins was 51% in MS and 28% in non-MS.
A threshold of 40.7% lesions with central veins resulted in 100% sensitivity and 73.9% specificity.
A test cohort of 10 patients with MS and 10 patients with microangiopathic lesions received 3-T T2*-weighted brain MRI.
Anonymised scans were analysed blind to clinical data, and simple diagnostic rules were devised.
These rules were applied to a validation cohort of 20 patients (13 with MS and 7 with microangiopathic lesions) by a blinded observer.
Within the test cohort, all patients with MS had central veins visible in >45% of brain lesions, while the rest had central veins visible in <45% of lesions.
By applying diagnostic rules to the validation cohort, all patients were correctly categorised.
Further reading
Further reading
Borrelli, S., et al. (2024) ‘Central vein sign, cortical lesions, and paramagnetic rim lesions for the diagnostic and prognostic workup of multiple sclerosis’, Neurology / Neuroimaging review (2024). Available at: https://pubmed.ncbi.nlm.nih.gov/38788180/
Cagol, A., Cortese, R., Barakovic, M., et al. (2024) ‘Diagnostic performance of cortical lesions and the central vein sign in multiple sclerosis’, JAMA Neurology, 81(2), pp. 143–153. Available at: https://pubmed.ncbi.nlm.nih.gov/38079177/
Okromelidze, L., P., et al. (2024) ‘Central Vein Sign in Multiple Sclerosis: a comparison study of the diagnostic performance of 3T versus 7T MRI’, American Journal of Neuroradiology, 45(1), pp. 76–?. Available at: https://pubmed.ncbi.nlm.nih.gov/38164557/
Daboul, L., Rooney, W.D., Sati, P., et al. (2023) ‘Effect of gadolinium-based contrast agent use on detection and diagnostic performance of the central vein sign: evaluation using a 3-T FLAIR* sequence in patients with suspected multiple sclerosis’, AJR American Journal of Roentgenology, 220(1), pp. 115–125. Available at: https://pubmed.ncbi.nlm.nih.gov/35975888/
La Rosa, F., et al. (2022) ‘Cortical lesions, central vein sign, and paramagnetic rim lesions in multiple sclerosis: emerging machine-learning techniques and future avenues’, Journal / Review (2022). Available at: https://pubmed.ncbi.nlm.nih.gov/36201950/
Al-Louzi, O., Blevins, G.A., Lin, F., et al. (2022) ‘Central vein sign profile of newly developing lesions in multiple sclerosis: a 3-year longitudinal study’, Neurology, (2022). Available at: https://pubmed.ncbi.nlm.nih.gov/35027474/
Kaisey, M., Reich, D.S., Solomon, A.J., et al. (2021) ‘Preventing multiple sclerosis misdiagnosis using the “central vein sign”: a real-world study’, Neurology (2021). Available at: https://pubmed.ncbi.nlm.nih.gov/33444958/
Guisset, F., Lolli, V., Bugli, C., et al. (2021) ‘The central vein sign in multiple sclerosis patients with vascular comorbidities’, Multiple Sclerosis Journal, 27(7), pp. 1057–1065. Available at: https://pubmed.ncbi.nlm.nih.gov/32749948/
Castellaro, M., Tamanti, A., Pisani, A.I., Pizzini, F.B., Crescenzo, F. and Calabrese, M. (2020) ‘The use of the central vein sign in the diagnosis of multiple sclerosis: a systematic review and meta-analysis’, Diagnostics (Basel), 10(12):1025. Available at: https://pubmed.ncbi.nlm.nih.gov/33260401/
Suh, C.H., Kim, S.J., Jung, S.C., Choi, C.G. and Kim, H.S. (2019) ‘The “Central Vein Sign” on T2*-weighted images as a diagnostic tool in multiple sclerosis: a systematic review and meta-analysis using individual patient data’, Scientific Reports, 9(1):18188. Available at: https://pubmed.ncbi.nlm.nih.gov/31796822/
Solomon, A.J., Watts, R., Ontaneda, D., Absinta, M., Sati, P. and Reich, D.S. (2018) ‘Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm’, Multiple Sclerosis Journal, 24(6), pp. 750–757. Available at: https://pubmed.ncbi.nlm.nih.gov/28820013/
Maggi, P., Absinta, M., Sati, P., et al. (2018) ‘Central vein sign differentiates multiple sclerosis from central nervous system inflammatory vasculopathies’, Annals of Neurology, 83(2), pp. 283–294. Available at: https://pubmed.ncbi.nlm.nih.gov/29328521/
Dworkin, J.D., Sati, P., Solomon, A., et al. (2018) ‘Automated integration of multimodal MRI for the probabilistic detection of the central vein sign in white matter lesions’, American Journal of Neuroradiology, 39(10), pp. 1806–1813. Available at: https://pubmed.ncbi.nlm.nih.gov/30213803/
Sparacia, G., Agnello, F., Gambino, A., Sciortino, M. and Midiri, M. (2018) ‘Multiple sclerosis: high prevalence of the “central vein” sign in white matter lesions on susceptibility-weighted images’, Neuroradiology Journal, 31(4), pp. 356–361. Available at: https://pubmed.ncbi.nlm.nih.gov/29565219/
Mistry, N., Dixon, J., Tallantyre, E., Tench, C., Abdel-Fahim, R., Jaspan, T., Morgan, P.S., Morris, P. and Evangelou, N. (2013) ‘Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain’, JAMA Neurology, 70(5), pp. 623–628. Available at: https://pubmed.ncbi.nlm.nih.gov/23529352/
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