Dr Jens WuerfulJens Wuerful, MD
Using 3T magnetic resonance imaging (MRI), use of the central vein sign as a biomarker for multiple sclerosis (MS) diagnosis showed promise in a recent cross-sectional study, with the biomarker displaying high specificity in differentiating MS from non-MS.

Among the 606 participants included, there were 4447 lesions imaged, and use of the central vein sign resulted in a sensitivity of 68.1% and a specificity of 82.9% in distinguishing cases of MS. The study authors, including Jens Wuerful, MD, of the Medical Image Analysis Center, and colleagues used a 35% proportion threshold for the measurement.

“The application of T2*-weighted imaging may further increase the sensitivity of the central vein sign,” Wuerful and colleagues detailed. “We propose the conduct of a large prospective study of the central vein sign in patients with symptoms suggestive of MS to confirm this study’s cross-sectional findings and to identify whether central vein sign–based criteria can be used in clinical practice to support the diagnosis of MS.”

Physician knowledge of the central vein is longstanding, though advances in MRI techniques have allowed for 7T MRI to visualize, in detail, a central vein within MS lesions, which was then discovered to provide almost-perfect differentiation between MS and unspecific white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or Susac syndrome. “Moreover, the central vein sign was observed in equal frequency in patients with RRMS and primary-progressive MS,” the authors noted.

In the study, a positive for central vein sign was observed in 47.4% (n = 1335; median, 50%; range 0%–100%) of the 2815 relapsing MS lesions examined, and in 54.2% (n = 374; median, 60%; range, 0%–100%)) of 690 clinically isolated syndrome lesions. All told, 91.3% (n = 295) of 323 patients with MS and clinically isolated syndrome had ≥1 lesion with a central vein, and ≥2 lesions with a central vein were found in 76.2% (n = 246) of these patients. At least 3 such lesions were found in 61.9% (n = 200) of patients.

In those without MS, a central vein sign was identified in 15.7% (n = 148) of the 942 non-MS lesions (median, 0%; range, 0%–100%). Of the 164 participants without MS but with lesions, 54.9% (n = 90) did not have a lesion with a central vein. Overall, 45.1% (n = 74) had ≥1 lesion, 20.7% (n = 34) had ≥2 lesions, and 11% (n = 18) had ≥3 lesions with central veins.

“We observed a high proportion of central veins in the lesions of patients with clinically isolated syndrome and relapsing MS but not in patients with MS mimics such as cerebral small vessel disease-associated brain lesions, migraine, NMOSD, or [systemic lupus erythematosus],” Wuerful and colleagues wrote.

The presence of ≥3 central vein sign lesions resulted in a sensitivity of 61.9% and specificity of 89.0% in differentiating MS and clinically isolated syndrome from not MS, while the combination of the 3-lesion criteria and the 35% central vein sign proportion threshold was associated with a higher sensitivity (83.0%), but lower specificity (68.3%).

The authors acknowledged a limitation in that that they observed a reduction in specificity for detecting MS for proportion-based—not for lesion-based—central vein sign criteria in individuals with minimal brain lesions. This, they explained, “is further complicated given that not all brain lesions can be reliably analyzed for the existence of the central vein sign.”

Additionally, a central vein on 3T MRI, when compared to 7T MRI, is difficult to visualize. Wuerful and others found that the sensitivity and specificity in detecting veins were highest with optimized T2*-weighted images. When a combined susceptibility-weighted imaging (SWI) and fluid-attenuated inversion recovery (FLAIR) approach was applied, the sensitivity and specificity were much lower. “Nonetheless, the T2*-weighted imaging was applied only in a small subgroup of 30 participants, and hence the comparison between FLAIR or SWI and T2*-weighted sequences is not generalizable,” they wrote.

Earlier this year, Pascal Sati, PhD, senior preclinical and clinical imaging scientist, National Institute of Neurological Disorders and Stroke (NINDS), and Daniel Ontaneda, MD, staff neurologist, Mellen Center, Cleveland Clinic, among others, presented on the biomarker. They are working together to develop a prospective study to determine if the central vein sign can have a positive impact on the time to get an accurate diagnosis of MS. Additionally, Sati is working with a group to attempt to validate another not-so-far-along biomarker, the paramagnetic rim sign, which may be able to help physicians identify chronic, active inflammation.

Watch Sati speak with NeurologyLive in an interview about this ongoing work below.

REFERENCE
Sinnecker T, Clarke MA, Meier D, et al. Evaluation of the Central Vein Sign as a Diagnostic Imaging Biomarker in Multiple Sclerosis. JAMA Neurol. Published online August 19, 2019. doi:10.1001/jamaneurol.2019.2478.