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Immunology Nov 2021Ectopic lymphoid follicles (ELFs), resembling germinal centre-like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be... (Review)
Review
Ectopic lymphoid follicles (ELFs), resembling germinal centre-like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be found in the meninges of around 40% of the investigated progressive multiple sclerosis (MS) post-mortem brain tissues and are associated with the severity of cortical degeneration and clinical disease progression. Of predominant importance for progressive neuronal damage during the progressive MS phase appears to be meningeal inflammation, comprising diffuse meningeal infiltrates, B-cell aggregates and compartmentalized ELFs. However, the absence of a uniform definition of ELFs impedes reproducible and comparable neuropathological research in this field. In this review article, we will first highlight historical aspects and milestones around the discovery of ELFs in the meninges of progressive MS patients. In the next step, we discuss how animal models may contribute to an understanding of the mechanisms underlying ELF formation. Finally, we summarize challenges in investigating ELFs and propose potential directions for future research.
Topics: Animals; B-Lymphocytes; Disease Models, Animal; Humans; Meninges; Multiple Sclerosis, Chronic Progressive; Tertiary Lymphoid Structures
PubMed: 34293193
DOI: 10.1111/imm.13395 -
Arquivos de Neuro-psiquiatria Nov 2022Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the... (Review)
Review
BACKGROUND
Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce.
OBJECTIVE
To critically review the literature on CM and propose a rational approach in the Brazilian scenario.
METHODS
Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil.
RESULTS
In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data.
CONCLUSION
We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.
Topics: Humans; Brazil; Meningitis; Syndrome; Neurocysticercosis; Neurosyphilis
PubMed: 36577417
DOI: 10.1055/s-0042-1758645 -
Journal of Immunology (Baltimore, Md. :... Jan 2020At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding... (Review)
Review
At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding the CNS host diverse populations of immune cells that influence how CNS-related immune responses develop. Interstitial and cerebrospinal fluid produced in the CNS is continuously drained, and recent advances have emphasized that this process is largely taking place through the lymphatic system. To what extent this fluid process mobilizes CNS-derived Ags toward meningeal immune cells and subsequently the peripheral immune system through the lymphatic vessel network is a question of significant clinical importance for autoimmunity, tumor immunology, and infectious disease. Recent advances in understanding the role of meningeal lymphatics as a communicator between the brain and peripheral immunity are discussed in this review.
Topics: Animals; Brain; Central Nervous System; Humans; Immunologic Surveillance; Lymphatic Vessels; Meninges
PubMed: 31907271
DOI: 10.4049/jimmunol.1900838 -
Frontiers in Immunology 2024
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Antitubercular Agents; Disease Management
PubMed: 38933279
DOI: 10.3389/fimmu.2024.1433345 -
Clinical and Translational Medicine Nov 2022The central nervous system (CNS) hosts a variety of immune cells, including two distinct macrophage populations: microglia are found in the parenchyma, whereas... (Review)
Review
The central nervous system (CNS) hosts a variety of immune cells, including two distinct macrophage populations: microglia are found in the parenchyma, whereas CNS-associated macrophages (CAMs) cover the CNS interfaces, such as the perivascular spaces, the meninges and the choroid plexus. Recent studies have given novel insights into the nature of CAMs as compared to microglia. In this mini-review, we summarise the current knowledge about the ontogenetic relationship and the underlying mechanism for the establishment of CNS macrophages during development.
Topics: Central Nervous System; Macrophages; Microglia; Meninges; Choroid Plexus
PubMed: 36336786
DOI: 10.1002/ctm2.1096 -
Proceedings of the National Academy of... Sep 2021Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin...
Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.
Topics: Animals; B-Lymphocytes; Cell Communication; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Female; Germinal Center; Inflammation; Lymphocyte Activation; Male; Meninges; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Neuroinflammatory Diseases; Parenchymal Tissue; Proto-Oncogene Proteins c-bcl-6; Th17 Cells
PubMed: 34479995
DOI: 10.1073/pnas.2023174118 -
Cells Aug 2022Migraines constitute a common neurological and headache disorder affecting around 15% of the world's population. In addition to other mechanisms, neurogenic... (Review)
Review
Migraines constitute a common neurological and headache disorder affecting around 15% of the world's population. In addition to other mechanisms, neurogenic neuroinflammation has been proposed to play a part in migraine chronification, which includes peripheral and central sensitization. There is therefore considerable evidence suggesting that inflammation in the intracranial meninges could be a key element in addition to calcitonin gene-related peptide (CGRP), leading to sensitization of trigeminal meningeal nociceptors in migraines. There are several studies that have utilized this approach, with a strong focus on using inflammatory animal models. Data from these studies show that the inflammatory process involves sensitization of trigeminovascular afferent nerve terminals. Further, by applying a wide range of different pharmacological interventions, insight has been gained on the pathways involved. Importantly, we discuss how animal models should be used with care and that it is important to evaluate outcomes in the light of migraine pathology.
Topics: Animals; Calcitonin Gene-Related Peptide; Inflammation; Meninges; Migraine Disorders; Nociceptors
PubMed: 35954288
DOI: 10.3390/cells11152444 -
Neuroimaging Clinics of North America Feb 2023Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic... (Review)
Review
Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic imaging patterns help radiologists distinguish different types of intracranial infections including meningitis and cerebritis from a variety of bacterial, viral, fungal, and/or parasitic causes. Here, we describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis. We discuss various imaging modalities and recent diagnostic advances such as deep learning through a survey of intracranial pathogens and their radiographic findings. Moreover, we explore critical complications and differential diagnoses of intracranial infections.
Topics: Humans; Neuroimaging; Meningitis; Diagnosis, Differential
PubMed: 36404039
DOI: 10.1016/j.nic.2022.07.001 -
Seizure Apr 2023Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients.... (Review)
Review
Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients. Tuberculous meningitis (TBM) and tuberculomas are the two forms of CNS tuberculosis that can present with seizures. Seizures usually resolve after successful treatment of the underlying infection. However, the success of the treatment is usually based on an early diagnosis. Delay in the treatment of CNS tuberculosis increases the risk of its associated complications, such as stroke. This would lead to the development of epilepsy. Early seizures may be related to meningeal irritation and cerebral edema, whereas late seizures are often associated with structural brain lesions that generally require more advanced and prolonged treatment. Risk factors associated with the development of epilepsy include young age, refractory seizures, tuberculoma, cortical involvement, epileptiform discharges, and residual lesions. Treatment of CNS tuberculosis is based on early initiation of appropriate anti-tuberculous drugs, antiseizure medications, and correction of associated predisposing factors. Finally, further research into the mechanisms of seizures and the development of epilepsy in CNS tuberculosis could help improve management of these conditions.
Topics: Child; Humans; Tuberculosis, Central Nervous System; Tuberculosis, Meningeal; Epilepsy; Seizures; Risk Factors
PubMed: 36963243
DOI: 10.1016/j.seizure.2023.03.006 -
Stroke Jul 2021Fibroblasts are the most common cell type of connective tissues. In the central nervous system (CNS), fibroblast-like cells are mainly located in the meninges and... (Review)
Review
Fibroblasts are the most common cell type of connective tissues. In the central nervous system (CNS), fibroblast-like cells are mainly located in the meninges and perivascular Virchow-Robin space. The origins of these fibroblast-like cells and their functions in both CNS development and pathological conditions remain largely unknown. In this review, we first introduce the anatomic location and molecular markers of CNS fibroblast-like cells. Next, the functions of fibroblast-like cells in CNS development and neurological disorders, including stroke, CNS traumatic injuries, and other neurological diseases, are discussed. Third, current challenges and future directions in the field are summarized. We hope to provide a synthetic review that stimulates future research on CNS fibroblast-like cells.
Topics: Animals; Central Nervous System; Fibroblasts; Humans; Meninges; Nervous System Diseases; Stroke
PubMed: 33940953
DOI: 10.1161/STROKEAHA.120.033431