Neuroinflammation Imaging Approaches: Leptomeninges

Daniel M Harrison¹
¹Neurology, UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE, BALTIMORE, MD, United States

Synopsis

Meningeal inflammation occurs in multiple neurologic disorders, including multiple sclerosis. Recent data suggests that leptomeningeal enhancement (LME) on post-contrast FLAIR MRI may be seen in multiple sclerosis and other neuroinflammatory disorders. In this session, we will review the current data on LME in multiple sclerosis and other disorders.

Neuroinflammation Imaging Approaches: Leptomeninges
Daniel M. Harrison, MD
Associate Professor of Neurology
University of Maryland School of Medicine

Why do we care about the meninges in multiple sclerosis?
· Histopathologic data demonstrate infiltration of inflammatory cells, such as CD20+ B- and plasmacytoid cells, in the meninges of multiple sclerosis (MS) of all subtypes.1-3
· ~40-50% of patients with secondary progressive MS have follicles of ectopic lymphoid tissue in the meninges. Those with follicles have a greater cortical lesion burden, more rapid disability progression, and earlier time to death.4
· Meningeal pathology appears to be directly related to cortical neuronal loss and demyelination.5

Can we visualize meningeal inflammation in MS and other neuroinflammatory disorders on MRI?
· Post-contrast FLAIR MRI may be a marker of meningeal inflammation in MS. Delayed acquisition post-contrast 3T FLAIR MRI shows leptomeningeal enhancement (LME) in ~25% of patients with MS. Autopsy data correlates regions of LME with histopathologic inflammation in the meninges.6
· Post-contrast FLAIR MRI may show LME in up to 90% of patients with MS. LME on 7T MRI correlates with reduced cortical volumes and thickness.7,8
· LME on FLAIR is not specific to MS. Seen also in neuromyelitis optica, chronic human t-cell lymphocytic virus infection, HIV, and neurologic/rheumatologic overlap syndromes such as Sjogren syndrome.9,10

Where do we go from here?
· Can LME be used as a treatment outcome measure? Initial data from a small study on primary progressive MS treated with intrathecal rituximab showed no change in LME.11 More study may be needed.
· Further study may be needed to determine ideal contrast agents, timing of contrast administration, and comparison between field strengths.
· Further study may be needed to confirm the relationship between LME and meningeal inflammation. Unclear if lymphatics may play a role and if LME is related to follicles or general inflammation.

Acknowledgements

No acknowledgement found.

References

1. Howell OW, Reeves CA, Nicholas R, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain. 2011;134(Pt 9):2755-2771.

2. Choi SR, Howell OW, Carassiti D, et al. Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis. Brain. 2012;135(Pt 10):2925-2937.

3. Lucchinetti CF, Popescu BF, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med. 2011;365(23):2188-2197.

4. Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain. 2007;130(Pt 4):1089-1104.

5. Magliozzi R, Howell OW, Reeves C, et al. A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010;68(4):477-493.

6. Absinta M, Vuolo L, Rao A, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology. 2015;85(1):18-28.

7. Harrison DM, Wang KY, Fiol J, et al. Leptomeningeal Enhancement at 7T in Multiple Sclerosis: Frequency, Morphology, and Relationship to Cortical Volume. J Neuroimaging. 2017;27(5):461-468. 8. Ighani M, Jonas S, Izbudak I, et al. No association between cortical lesions and leptomeningeal enhancement on 7-Tesla MRI in multiple sclerosis. Mult Scler. 2019:1352458519876037.

9. Absinta M, Cortese IC, Vuolo L, et al. Leptomeningeal gadolinium enhancement across the spectrum of chronic neuroinflammatory diseases. Neurology. 2017;88(15):1439-1444.

10. Asgari N, Flanagan EP, Fujihara K, et al. Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2017;4(4):e343.

11. Bhargava P, Wicken C, Smith MD, et al. Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement. Mult Scler Relat Disord. 2019;30:136-140.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)