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

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.