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Leptomeningeal inflammation in multiple sclerosis: Insights from animal and human studies

Published:September 22, 2018DOI:https://doi.org/10.1016/j.msard.2018.09.025

      Highlights

      • LMI is associated with worse clinical and pathological outcomes in MS.
      • B cells appear to play a critical role in LMI.
      • Post-contrast T2-FLAIR MRI can potentially identify areas of LMI in MS patients.
      • Multiple trials are attempting to target LMI to potentially slow disease progression.

      Abstract

      The presence of leptomeningeal inflammation (LMI) in MS was first identified in 2004 and multiple subsequent studies have confirmed the presence of immune cell collections in the meninges of a subset of MS patients. Pathologically, LMI can range from disorganized immune cell collections in the meninges of patients with relapsing remitting (RRMS) or primary progressive MS (PPMS) to well-organized ectopic lymphoid follicles in secondary progressive MS (SPMS). The presence of LMI has been linked to worse pathological (increased cortical demyelination and neuroaxonal damage) and clinical (earlier age at onset, more rapid progression, shorter time to death) outcomes. Recent studies have also demonstrated the ability of specific MRI sequences to detect areas of leptomeningeal contrast enhancement (LME) which may correspond pathologically to areas of LMI. We summarize findings from both pathological and radiological studies of LMI in MS. We also provide a brief overview of LMI in animal models of MS (experimental autoimmune encephalomyelitis) and ongoing clinical trials attempting to target LMI. Future research will help clarify the role of LMI in MS disease progression, identify the mechanisms through which LMI may contribute to MS pathology and test new approaches to target LMI.

      Keywords

      Abbreviations:

      BAFF (B cell activating factor), CXCL13 (C-X-C motif chemokine 13), CXCL10 (C-X-C motif chemokine 10), EAE (Experimental autoimmune encephalomyelitis), ELF (Ectopic lymphoid follicle-like structures), FDA (Food and Drug Administration), HTLV-1 (Human T-cell Lymphotropic virus-1), IL-6 (Interleukin 6), IL-10 (Interleukin 10), IL-17 (Interleukin 17), IL-22 (Interleukin 22), LME (Leptomeningeal contrast enhancement), LMI (Leptomeningeal inflammation), LTα (Lymphotoxin alpha), MOG (Myelin oligodendrocyte glycoprotein), PNAd (Peripheral node addressin), T2-FLAIR (T2 weighted fluid attenuated inversion recovery), TNF (Tumor necrosis factor)
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