Impaired Meningeal Lymphatic Flow in NMOSD Patients With Acute Attack

Xinxin Wang, Haiyan Tian, Han Liu, Dongxiao Liang, Chi Qin, Qingyong Zhu, Lin Meng, Yu Fu, Shuqin Xu, Yanping Zhai, Xuebing Ding, Xuejing Wang, Xinxin Wang, Haiyan Tian, Han Liu, Dongxiao Liang, Chi Qin, Qingyong Zhu, Lin Meng, Yu Fu, Shuqin Xu, Yanping Zhai, Xuebing Ding, Xuejing Wang

Abstract

The meningeal lymphatic vessels (mLVs) in central nervous system (CNS) have been validated by rodent and human studies. The mLVs play a vital role in draining soluble molecules and trafficking lymphocytes, antigens and antibodies from CNS into cervical lymph nodes (CLNs). This indicates that mLVs may serve as a link between the CNS and peripheral immune system, perhaps involving in the neuroinflammatory disease. However, the morphology and drainage function of mLVs in patients with neuroinflammatory disease, such as neuromyelitis optica spectrum disorders (NMOSD), remains unexplored. Using the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we found that slower flow through mLVs along superior sagittal sinus in NMOSD patients with acute attack instead of NMOSD patients in chronic phase. The reduced flow in mLVs correlated with the disease severity evaluated by expanded disability status scale (EDSS). The receiver operating characteristic curve (ROC) indicated DCE-MRI might provide objective evidence to predict the acute relapse of NMOSD through evaluating the function of mLVs. Promoting or restoring the function of mLVs might be a new target for the treatment of NMOSD relapse.

Keywords: DCE-MRI; acute relapse; meningeal lymphatic vessels; neuromyelitis optica spectrum disorders; superior sagittal sinus.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Wang, Tian, Liu, Liang, Qin, Zhu, Meng, Fu, Xu, Zhai, Ding and Wang.

Figures

Figure 1
Figure 1
Quantitative assessment of mLVs-SSS flow by DCE-MRI. (A) Representative DCE-MRI images of the mLVs-SSS (L-mLVs-SSS, R- mLVs-SSS and Lo- mLVs-SSS) before (a, c, e) and after (b, d, f) vascular administration of the gadobutrol in NC (a, b), ANMOSD (c, d), and CNMOSD (e, f) groups. scale bar, 2 cm. The red rectangles stand for the mLVs-SSS. L-mLVs-SSS, R- mLVs-SSS and Lo- mLVs-SSS represented the left, right and lower mLVs-SSS, respectively. The representative time-intensity curves (TIC) in NC (g), ANMOSD (h), and CNMOSD (i) were obtained by DCE-MRI images. (B) Comparison of the TTP (a–c), wash-in rate (d–f), and AUC (g–i) of mLVs-SSS in NC, ANMOSD, and CNMOSD groups. (C) The TTP (a–c), wash-in rate (d–f), and AUC (g–i) of mLVs-SSS in NC and ANMOSD patients (I-ANMOSD group, II-ANMOSD group) were further compared. I-ANMOSD group, EDSS scale ≤ 4.5; II-ANMOSD group, EDSS scale > 4.5. TTP, time to peak; AUC, area under curve.
Figure 2
Figure 2
Correlation between EDSS scales and DCE-MRI parameters, and the diagnostic accuracy of DCE-MRI parameters. (A) Correlations between the EDSS stage and the TTP (a–c), wash-in rate (d–f), and AUC (g–i) of mLVs-SSS in ANMOSD patients. The parameters were correlated with the EDSS stage. (B) Receiver operating characteristic (ROC) curve of the TTP (a–c), wash-in rate (d–f), and AUC (g–i) of mLVs-SSS in distinguishing ANMOSD from CNMOSD group. (C) ROC of the TTP (a–c), wash-in rate (d–f), and AUC (g–i) of mLVs-SSS in distinguishing I-ANMOSD group from CNMOSD group.
Figure 3
Figure 3
Visualization and measurement of mLVs-SSS in different groups by high-solution MRI sequences. (A) Visualization of mLVs-SSS in NC (a, d), ANMOSD (b, e), and CNMOSD (c, f) by 2D T1 black-blood (a–c) and 3D T2 flair (d–f) sequence. The red rectangles stand for the three mLVs-SSS (L-mLVs-SSS, R-mLVs-SSS, Lo-mLVs-SSS), L-mLVs-SSS, R-mLVs-SSS and Lo- mLVs-SSS represents the left, right and lower mLVs-SSS, respectively. Scale bar, 2 cm. (B) Measurement and comparison of the cross-sectional area of mLVs-SSS in different MRI sequences. The cross-sectional area of mLVs-SSS in three groups (NC, ANMOSD, CNMOSD) were not significantly different with each group in 2D T1 black-blood (a), 3D T1 black-blood (b) and 3D T2 flair (c) sequences. The cross-sectional area of mLVs-SSS in NC and ANMOSD patients (I-ANMOSD group, II-ANMOSD group) in 2D T1 black-blood (d), 3D T1 black-blood (e) and 3D T2 flair (f) sequences. There was no difference between groups in all MRI sequences. I-ANMOSD group, EDSS stage ≤ 4.5; II-ANMOSD group, EDSS stage > 4.5. (C) Correlations between the EDSS scale and the cross-sectional area of mLVs-SSS in ANMOSD patients in 2D T1 black-blood (a–c), 3D T1 black-blood (d–f) and 3D T2 flair (g–i) sequences. The cross-sectional area of mLVs-SSS was not correlated with the EDSS scale.

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