CENTRAL VEIN SIGN ASSESSMENT IN MULTIPLE SCLEROSIS: A MULTI-PARAMETRIC APPROACH

Abstract

Title: Central Vein Sign Assessment in Multiple Sclerosis: A Multi-Parametric Approach

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease that affects myelinated neurons in the central nervous system. The cause of multiple sclerosis remains unknown. Heredity, infections, and autoimmunity, combined or alone, may be involved in the development of multiple sclerosis. Some hypotheses suggest that in genetically predisposed individuals, a breach in the blood-brain barrier triggers a sequence of immune-mediated events that eventually lead to the pathophysiological changes characteristic to multiple sclerosis. The diagnosis of multiple sclerosis is based on clinical examination findings and evidence ancillary tests such as magnetic resonance imaging (MRI), evoked potentials test and lumbar puncture. Due to the lack of a test that can provide a definitive diagnosis, multiple sclerosis is often incorrectly diagnosed in patients with conditions that have clinical features similar to those of the disease. Many studies have been conducted to assess the evolution of multiple sclerosis lesions to gain better understanding of the pathophysiological mechanisms that lead to blood brain barrier disruption and lesion formation in multiple sclerosis. However, only few studies assessed the early natural development of multiple sclerosis lesions using short interval longitudinal magnetic resonance imaging. There are no studies yet that addresses the pathophysiological changes of the central vein sign (CVS) lesions on untreated multiple sclerosis patients. Research aimed to improve the diagnosis of multiple sclerosis has led to introduce the central vein sign (CVS) as an MRI biomarker that can differentiate multiple sclerosis (MS) from other white matter diseases that mimic it.

Aim: The main objective of this study is to investigate the pathophysiological mechanisms of the central vein sign lesions (CVS) using diffusion tensor imaging (DTI) in 4 untreated patients with relapsing-remitting multiple sclerosis.

Materials and Methods: Four untreated patients with early relapsing-remitting MS were followed weekly for two months. MR protocol included the following sequences: a sagittal 3D-fluid-attenuated inversion recovery (FLAIR), a 3D-T1 post-gadolinium contrast, and a susceptibility-weighted imaging (SWI). DTI was also acquired at each follow-up visit. Lesions were segmented on all eight scans on FLAIR images and then labeled as CVS positive or negative based on their appearance on SWI. The volumes of each lesion as well as DTI metrics values were reported and analyzed using repeated measure ANOVA with Bonferroni correction.

Results: CVS+ lesions’ volume was superior to the CVS- lesions’ volume in the newly appearing lesions and this result can be attributed to the anatomy of these lesions. Moreover, in all the lesions evaluated, CVS+ lesions appeared to be more enhanced than CVS- lesions. This study also found that new lesions were not enhanced while old lesions which had reactivated showed rim-enhancement, an aspect characteristic to chronic active lesions. With regards to the DTI metrices, no significant differences were noted in the FA values of the old lesions, but it was noted that CVS+ lesions have higher FA than CVS- lesions, which can be explained by laminar blood flow in the vein running through the CVS+ lesion, resulting in a more organized lesion.

Conclusion: CVS+ and CVS- lesions can enhance on T1Gd. New lesions are more likely to be GD enhanced. Newly developing CVS+ lesions were more likely to be Gd enhanced lesions. The larger lesions are more likely to be newly Gd enhanced lesions. Rim lesions are more likely to be the old lesions. DTI matrices(FA,AD, RD) were not found significant in all lesions.

Keywords: Multiple Sclerosis, Central Vein Sign, Diffusion Tensor Imaging, Magnetic Resonance Imaging