TY - JOUR
T1 - Leptomeningeal inflammation in multiple sclerosis
T2 - Insights from animal and human studies
AU - Wicken, Cassie
AU - Nguyen, James
AU - Karna, Rahul
AU - Bhargava, Pavan
N1 - Funding Information:
Dr. Bhargava reports grants from National Multiple Sclerosis Society, grants from Race to Erase MS, grants from American Academy of Neurology, during the conduct of the study; grants from Department of Defense, grants from Conrad N Hilton Foundation, outside the submitted work;
Funding Information:
This work was supported by a Career Transition Award from the National MS Society to PB and the John F Kurtzke Clinician Scientist Development award from the American Academy of Neurology to PB.
Publisher Copyright:
© 2018 Elsevier B.V.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - B cells
KW - Leptomeningeal inflammation
KW - Progressive MS
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U2 - 10.1016/j.msard.2018.09.025
DO - 10.1016/j.msard.2018.09.025
M3 - Review article
C2 - 30268038
AN - SCOPUS:85053826615
SN - 2211-0348
VL - 26
SP - 173
EP - 182
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
ER -