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      Pregnancy-Related Immune Changes and Demyelinating Diseases of the Central Nervous System

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          Abstract

          Demyelinating diseases of the central nervous system comprise a heterogeneous group of autoimmune disorders characterized by myelin loss with relative sparing of axons occurring on a background of inflammation. Some of the most common demyelinating diseases are multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. Besides showing clinical, radiological, and histopathological features that complicate their diagnosis, demyelinating diseases often involve different immunological processes that produce distinct inflammatory patterns. Evidence of demyelination diseases derives mostly from animal studies of experimental autoimmune encephalomyelitis (EAE), a model that relies on direct antibody–antigen interactions induced by encephalitogenic T cells. Pregnancy is characterized by non-self-recognition, immunomodulatory changes and an altered Th1/Th2 balance, generally considered a Th2-type immunological state that protects the mother from infections. During pregnancy, the immune response of patients with autoimmune disease complicated with pregnancy is different. Immune tolerance in pregnancy may affect the course of some diseases, which may reach remission or be exacerbated. In this review, we summarize current knowledge on the immune status during pregnancy and discuss the relationship between pregnancy-related immune changes and demyelinating diseases of the central nervous system.

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          Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?

          Pregnant females are susceptible to intracellular pathogens and are biased towards humoral rather than cell-mediated immunity. Since TH1 cytokines compromise pregnancy and TH2 cytokines are produced at the maternal-fetal interface, we hypothesize that these TH2 cytokines inhibit TH1 responses, improving fetal survival but impairing responses against some pathogens.
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            Role of the innate and adaptive immune responses in the course of multiple sclerosis.

            Multiple sclerosis is a chronic disease of the CNS that leads to substantial disability in most patients. The early phase is characterised by relapses and the later phase by progressive disability. Results from immunological, genetic, and histopathological studies and treatment trials have shown that the immune system plays a key part in the disease course. Findings from animal models and immunological studies of patients with multiple sclerosis suggest a change in the involvement of the immune system during disease initiation and progression. These findings suggest that a peripheral immune response targeting the CNS drives the disease process during the early phase, whereas immune reactions within the CNS dominate the progressive phase. These concepts for the differential involvement of immune responses in the early and progressive phase of this disease have important implications for future research in the pathogenesis and treatment of multiple sclerosis.
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              Acute disseminated encephalomyelitis.

              Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurologic signs and deficits. Children are preferentially affected. In the absence of specific biologic markers, the diagnosis of ADEM is still based on the clinical and radiologic features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS). The International Pediatric MS Study Group proposes uniform definitions for ADEM and its variants. We discuss some of the difficulties in the interpretation of available literature due to the different terms and definitions used. In addition, this review summarizes current knowledge of the main aspects of ADEM, including its clinical and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An overview of ADEM treatment in children is provided. Finally, the controversies surrounding pediatric MS and ADEM are addressed.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                09 October 2019
                2019
                : 10
                : 1070
                Affiliations
                Department of Neurology, The Second Xiangya Hospital, Central South University , Changsha, China
                Author notes

                Edited by: Pamela Ann McCombe, University of Queensland, Australia

                Reviewed by: Jennifer Graves, University of California, San Diego, United States; Anneke Van Der Walt, The University of Melbourne, Australia

                *Correspondence: Wei Lu luwei0338@ 123456csu.edu.cn

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2019.01070
                6794637
                31649614
                9b61f813-d629-41f4-9686-c1518e26e565
                Copyright © 2019 Qiu, He, Chen, Liu, Deng and Lu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 March 2019
                : 23 September 2019
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 125, Pages: 12, Words: 9144
                Categories
                Neurology
                Review

                Neurology
                demyelinating diseases,pregnancy,multiple sclerosis,acute disseminated encephalomyelitis,neuromyelitis optica spectrum disorders

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