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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 -
Cells Apr 2021The lymphatic system serves key functions in maintaining fluid homeostasis, the uptake of dietary fats in the small intestine, and the trafficking of immune cells.... (Review)
Review
The lymphatic system serves key functions in maintaining fluid homeostasis, the uptake of dietary fats in the small intestine, and the trafficking of immune cells. Almost all vascularized peripheral tissues and organs contain lymphatic vessels. The brain parenchyma, however, is considered immune privileged and devoid of lymphatic structures. This contrasts with the notion that the brain is metabolically extremely active, produces large amounts of waste and metabolites that need to be cleared, and is especially sensitive to edema formation. Recently, meningeal lymphatic vessels in mammals and zebrafish have been (re-)discovered, but how they contribute to fluid drainage is still not fully understood. Here, we discuss these meningeal vessel systems as well as a newly described cell population in the zebrafish and mouse meninges. These cells, termed brain lymphatic endothelial cells/Fluorescent Granular Perithelial cells/meningeal mural lymphatic endothelial cells in fish, and Leptomeningeal Lymphatic Endothelial Cells in mice, exhibit remarkable features. They have a typical lymphatic endothelial gene expression signature but do not form vessels and rather constitute a meshwork of single cells, covering the brain surface.
Topics: Animals; Brain; Endothelial Cells; Humans; Lymphangiogenesis; Lymphatic System; Macromolecular Substances; Meninges
PubMed: 33918497
DOI: 10.3390/cells10040799 -
Journal of Neuroinflammation May 2024Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders... (Review)
Review
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.
Topics: Brain Injuries, Traumatic; Humans; Animals; Meninges; Neuroinflammatory Diseases; Neuroimmunomodulation
PubMed: 38802931
DOI: 10.1186/s12974-024-03122-7 -
Glymphatic-lymphatic coupling: assessment of the evidence from magnetic resonance imaging of humans.Cellular and Molecular Life Sciences :... Mar 2024The discoveries that cerebrospinal fluid participates in metabolic perivascular exchange with the brain and further drains solutes to meningeal lymphatic vessels have... (Review)
Review
The discoveries that cerebrospinal fluid participates in metabolic perivascular exchange with the brain and further drains solutes to meningeal lymphatic vessels have sparked a tremendous interest in translating these seminal findings from animals to humans. A potential two-way coupling between the brain extra-vascular compartment and the peripheral immune system has implications that exceed those concerning neurodegenerative diseases, but also imply that the central nervous system has pushed its immunological borders toward the periphery, where cross-talk mediated by cerebrospinal fluid may play a role in a range of neoplastic and immunological diseases. Due to its non-invasive approach, magnetic resonance imaging has typically been the preferred methodology in attempts to image the glymphatic system and meningeal lymphatics in humans. Even if flourishing, the research field is still in its cradle, and interpretations of imaging findings that topographically associate with reports from animals have yet seemed to downplay the presence of previously described anatomical constituents, particularly in the dura. In this brief review, we illuminate these challenges and assess the evidence for a glymphatic-lymphatic coupling. Finally, we provide a new perspective on how human brain and meningeal clearance function may possibly be measured in future.
Topics: Animals; Humans; Lymphatic Vessels; Central Nervous System; Brain; Meninges; Magnetic Resonance Imaging
PubMed: 38472405
DOI: 10.1007/s00018-024-05141-2 -
Cancer Control : Journal of the Moffitt... Jan 2017Neoplastic meningitis is a complication of solid and hematological malignancies. It consists of the spread of malignant cells to the leptomeninges and subarachnoid space... (Review)
Review
BACKGROUND
Neoplastic meningitis is a complication of solid and hematological malignancies. It consists of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid.
METHODS
A literature review was conducted to summarize the clinical presentation, differential diagnosis, laboratory values, and imaging findings of neoplastic meningitis.
RESULTS
Neoplastic meningitis is an event in the course of cancer with a variable clinical presentation and a wide differential diagnosis. In general, characteristic findings on gadolinium-enhanced magnetic resonance imaging and the presence of malignant cells in the cerebrospinal fluid remain the cornerstones of diagnosis. However, both modalities do not always confirm the diagnosis of neoplastic meningitis despite a typical clinical picture.
CONCLUSIONS
Clinicians treating patients with cancer should be aware of the possibility of neoplastic meningitis, especially when multilevel neurological symptoms are present. Neoplastic meningitis can be an elusive diagnosis, so clinician awareness is important so that this malignant manifestation is recognized in a timely manner.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Meningeal Neoplasms; Meningitis; Severity of Illness Index
PubMed: 28178708
DOI: 10.1177/107327481702400103 -
World Neurosurgery Oct 2020The extradural neural axis compartment (EDNAC) is an adipovenous zone located between the meningeal and endosteal layers of the dura and has been minimally investigated.... (Review)
Review
OBJECTIVE
The extradural neural axis compartment (EDNAC) is an adipovenous zone located between the meningeal and endosteal layers of the dura and has been minimally investigated. It runs along the neuraxis from the orbits down to the coccyx and contains fat, valveless veins, arteries, and nerves. In the present review, we have outlined the current knowledge regarding the structural and functional significance of the EDNAC.
METHODS
We performed a narrative review of the reported EDNAC data.
RESULTS
The EDNAC can be organized into 4 regional enlargements along its length: the orbital, lateral sellar, clival, and spinal segments, with a lateral sellar orbital junction linking the orbital and lateral sellar segments. The orbital EDNAC facilitates the movement of the eyeball and elsewhere allows limited motility for the meningeal dura. The major nerves and vessels are cushioned and supported by the EDNAC. Increased intra-abdominal pressure will also be conveyed along the spinal EDNAC, causing increased venous pressure in the spine and cranium. From a pathological perspective, the EDNAC functions as a low-resistance, extradural passageway that might facilitate tumor encroachment and expansion.
CONCLUSIONS
Clinicians should be aware of the extent and significance of the EDNAC, which could affect skull base and spine surgery, and have an understanding of the tumor spread pathways and growth patterns. Comparatively little research has focused on the EDNAC since its initial description. Therefore, future investigations are required to provide more information on this underappreciated component of neuraxial anatomy.
Topics: Adipose Tissue; Blood Vessels; Humans; Meninges
PubMed: 32711147
DOI: 10.1016/j.wneu.2020.07.095 -
Neurology Jul 2015To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated...
OBJECTIVE
To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.
METHODS
Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination.
RESULTS
Focal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination.
CONCLUSION
Leptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.
Topics: Gadolinium; Humans; Magnetic Resonance Imaging; Meninges; Meningitis; Multiple Sclerosis, Relapsing-Remitting
PubMed: 25888557
DOI: 10.1212/WNL.0000000000001587 -
PLoS Biology Nov 2023The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune...
The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection. Here, by combining single-cell transcriptomics and mass cytometry by time-of-flight (CyTOF) with in vivo interventions, we found that chronic T. brucei infection triggers the development of ectopic lymphoid aggregates (ELAs) in the murine meninges. These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells. Furthermore, the B cells found in the infected meninges produced high-affinity autoantibodies able to recognise mouse brain antigens, in a process dependent on LTβ signalling. A mid-throughput screening identified several host factors recognised by these autoantibodies, including myelin basic protein (MBP), coinciding with cortical demyelination and brain pathology. In humans, we identified the presence of autoreactive IgG antibodies in the cerebrospinal fluid (CSF) of second stage HAT patients that recognised human brain lysates and MBP, consistent with our findings in experimental infections. Lastly, we found that the pathological B cell responses we observed in the meninges required the presence of T. brucei in the CNS, as suramin treatment before the onset of the CNS stage prevented the accumulation of GL7+ CD95+ GC-like B cells and brain-specific autoantibody deposition. Taken together, our data provide evidence that the meningeal immune response during chronic T. brucei infection results in the acquisition of lymphoid tissue-like properties, broadening our understanding of meningeal immunity in the context of chronic infections. These findings have wider implications for understanding the mechanisms underlying the formation ELAs during chronic inflammation resulting in autoimmunity in mice and humans, as observed in other autoimmune neurodegenerative disorders, including neuropsychiatric lupus and multiple sclerosis.
Topics: Humans; Animals; Mice; Trypanosoma brucei brucei; Persistent Infection; Meninges; Trypanosomiasis, African; Lymphoid Tissue; Autoantibodies
PubMed: 37983289
DOI: 10.1371/journal.pbio.3002389 -
Journal of Neural Engineering Jan 2020Understanding how current reaches the brain during transcranial electrical stimulation (tES) underpins efforts to rationalize outcomes and optimize interventions. To...
OBJECTIVE
Understanding how current reaches the brain during transcranial electrical stimulation (tES) underpins efforts to rationalize outcomes and optimize interventions. To this end, computational models of current flow relate applied dose to brain electric field. Conventional tES modeling considers distinct tissues like scalp, skull, cerebrospinal fluid (CSF), gray matter and white matter. The properties of highly conductive CSF are especially important. However, modeling the space between skull and brain as entirely CSF is not an accurate representation of anatomy. The space conventionally modeled as CSF is approximately half meninges (dura, arachnoid, and pia) with lower conductivity. However, the resolution required to describe individual meningeal layers is computationally restrictive in an MRI-derived head model. Emulating the effect of meninges through CSF conductivity modification could improve accuracy with minimal cost.
APPROACH
Models with meningeal layers were developed in a concentric sphere head model. Then, in a model with only CSF between skull and brain, CSF conductivity was optimized to emulate the effect of meningeal layers on cortical electric field for multiple electrode positions. This emulated conductivity was applied to MRI-derived models.
MAIN RESULTS
Compared to a model with conventional CSF conductivity (1.65 S m), emulated CSF conductivity (0.85 S m) produced voltage fields better correlated with intracranial recordings from epilepsy patients.
SIGNIFICANCE
Conventional tES models have been validated using intracranial recording. Residual errors may nonetheless impact model utility. Because CSF is so conductive to current flow, misrepresentation of the skull-brain interface as entirely CSF is not realistic for tES modeling. Updating the conventional model with a CSF conductivity emulating the effect of the meninges enhances modeling accuracy without increasing model complexity. This allows existing modeling pipelines to be leveraged with a simple conductivity change. Using 0.85 S m emulated CSF conductivity is recommended as the new standard in non-invasive brain stimulation modeling.
Topics: Finite Element Analysis; Humans; Magnetic Resonance Imaging; Meninges; Models, Neurological; Skull; Transcranial Direct Current Stimulation
PubMed: 31689695
DOI: 10.1088/1741-2552/ab549d -
Theranostics 2023The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal...
The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aβ and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aβ from the brain. We investigated the effect of borneol on meningeal lymphatic clearance of macromolecules with different molecular weights (including Aβ) in the brain. To further investigate the mechanism of borneol regulating meningeal lymphatic drainage, immunofluorescence staining, western blotting, ELISA, RT-qPCR, and Nitric Oxide assay kits were used. The cognitive function of AD mice after borneol treatment was evaluated using two behavioral tests: open field (OF) and Morris water maze (MWM). This study discovered that borneol could accelerate the lymphatic clearance of Aβ from the brain by enhancing meningeal lymphatic drainage. Preliminary mechanism analysis revealed that borneol could improve the permeability and inner diameter of lymphatic vessels, allowing macromolecules to drain into the cervical lymph nodes (CLNS) and then be transported to the lymphatic circulation. To speed up the clearance of macromolecules, borneol also stimulated lymphatic constriction by lowering the level of nitric oxide in the meninges. In addition, borneol stimulated lymphangiogenesis by increasing the levels of FOXC2, VEGFC, and LYVE-1 in the meninges, which promoted the clearance rates of macromolecules. Borneol improved meningeal lymphatic clearance not only for Aβ but also for other macromolecular polymers (molecular weight in the range of 2 KD - 45 KD. Borneol ameliorated cognitive deficits and alleviated brain Aβ burden in Aβ-injected mice. Our findings not only provide a strategy to regulate lymphatic clearance pathways of macromolecules in the brain, but also new targets and ideas for treating neurodegenerative diseases like AD. Furthermore, our findings indicate that borneol is a promising therapeutic drug for AD.
Topics: Mice; Animals; Amyloid beta-Peptides; Alzheimer Disease; Nitric Oxide; Brain; Meninges; Mice, Transgenic
PubMed: 36593948
DOI: 10.7150/thno.76133