Autoimmune Disorders of the Nervous System: Pathophysiology, Clinical Features, and Therapy

Bhagavati, Satyakam

doi:10.3389/fneur.2021.664664

Cited by 56 publications

(32 citation statements)

References 132 publications

(125 reference statements)

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“…New developments in molecular biology, immunology, better understanding of neuroinflammatory responses and advances in neuroimaging have resulted in better insights into the pathophysiology and impact of neuroinflammation. The role of infections as triggers of autoimmunity in both the central and peripheral nervous systems is being unraveled ( 13 – 17 ). To turn the tide of the scourge of infectious diseases requires innovative approaches and research into the investigation and management of these post-infectious autoimmune disorders.…”

Section: Introductionmentioning

confidence: 99%

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

et al. 2022

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The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases.The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden.Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically “tropical” conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.

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Section: Introductionmentioning

confidence: 99%

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

et al. 2022

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“…Although the causes of its pathogenesis are not entirely clear, it is known that MS development is associated with a combination of genetic and environmental factors. Interestingly, genetic data suggest that the pathogenesis of MS shares important features with a variety of non-CNS autoimmune diseases [ 83 , 87 ]. Moreover, the existence of an increased intestinal permeability has also been highlighted as a potential cause of MS.…”

Section: Epilepsy In Neurodegenerative Diseasesmentioning

confidence: 99%

Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways

et al. 2021

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Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

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“…Central nervous system (CNS) autoimmune demyelinating disorders present with a broad clinical disease spectrum, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), anti-myelin oligodendrocyte glycoprotein-associated disease (MOGAD), acute disseminated encephalomyelitis (ADEM), and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis. The autoantigen is unknown in MS and ADEM, while it has been identified for NMSOD (aquaporin-4 water channel (AQP4)), MOGAD (myelin oligodendrocyte glycoprotein), and GFAP-associated meningoencephalomyelitis [ 1 , 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders

Allegretta

D’Amico

Manuti

et al. 2022

IJMS

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Autoimmune demyelinating diseases—including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis—are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications.

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Autoimmune Disorders of the Nervous System: Pathophysiology, Clinical Features, and Therapy

Cited by 56 publications

References 132 publications

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders

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