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Annual Review of Neuroscience Jul 2023Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the... (Review)
Review
Migraine is a complex neurovascular pain disorder linked to the meninges, a border tissue innervated by neuropeptide-containing primary afferent fibers chiefly from the trigeminal nerve. Electrical or mechanical stimulation of this nerve surrounding large blood vessels evokes headache patterns as in migraine, and the brain, blood, and meninges are likely sources of headache triggers. Cerebrospinal fluid may play a significant role in migraine by transferring signals released from the brain to overlying pain-sensitive meningeal tissues, including dura mater. Interactions between trigeminal afferents, neuropeptides, and adjacent meningeal cells and tissues cause neurogenic inflammation, a critical target for current prophylactic and abortive migraine therapies. Here we review the importance of the cranial meninges to migraine headaches, explore the properties of trigeminal meningeal afferents, and briefly review emerging concepts, such as meningeal neuroimmune interactions, that may one day prove therapeutically relevant.
Topics: Humans; Migraine Disorders; Meninges; Dura Mater; Headache; Brain
PubMed: 36913712
DOI: 10.1146/annurev-neuro-080422-105509 -
Infectious Diseases Now Nov 2023In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to... (Review)
Review
In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is >0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for.
Topics: Infant; Child; Humans; Infant, Newborn; Meningitis, Pneumococcal; Anti-Bacterial Agents; Streptococcus pneumoniae; Cefotaxime; Communicable Diseases
PubMed: 37741342
DOI: 10.1016/j.idnow.2023.104788 -
Ugeskrift For Laeger Jun 2024Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral...
Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral facial nerve palsy, ear pain and concurrent zoster rash in the ear canal. However, vesicles in the mouth can be seen. A rare complication of RHS is viral meningitis. This is a case report of a patient with orally manifested RHS and concurrent asymptomatic viral meningitis. This case aims to raise awareness of RHS with atypical presentation and concurrent viral meningitis and, thereby, the importance of a thorough neurological examination.
Topics: Humans; Herpes Zoster Oticus; Meningitis, Viral; Male; Female; Middle Aged
PubMed: 38903036
DOI: 10.61409/V02240092 -
Nature Communications Nov 2023Emerging evidence shows that the meninges conduct essential immune surveillance and immune defense at the brain border, and the dysfunction of meningeal immunity...
Emerging evidence shows that the meninges conduct essential immune surveillance and immune defense at the brain border, and the dysfunction of meningeal immunity contributes to aging and neurodegeneration. However, no study exists on the molecular properties of cell types within human leptomeninges. Here, we provide single nuclei profiling of dissected postmortem leptomeninges from aged individuals. We detect diverse cell types, including unique meningeal endothelial, mural, and fibroblast subtypes. For immune cells, we show that most T cells express CD8 and bear characteristics of tissue-resident memory T cells. We also identify distinct subtypes of border-associated macrophages (BAMs) that display differential gene expressions from microglia and express risk genes for Alzheimer's Disease (AD), as nominated by genome-wide association studies (GWAS). We discover cell-type-specific differentially expressed genes in individuals with Alzheimer's dementia, particularly in fibroblasts and BAMs. Indeed, when cultured, leptomeningeal cells display the signature of ex vivo AD fibroblasts upon amyloid-β treatment. We further explore ligand-receptor interactions within the leptomeningeal niche and computationally infer intercellular communications in AD. Thus, our study establishes a molecular map of human leptomeningeal cell types, providing significant insight into the border immune and fibrotic responses in AD.
Topics: Humans; Aged; Genome-Wide Association Study; Meninges; Alzheimer Disease; Macrophages; Aging; Microglia
PubMed: 37923721
DOI: 10.1038/s41467-023-42825-y -
Nature Apr 2024The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that...
The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that changes in the brain are often reflected in the eye, particularly in the retina. Still, the possibility of an immunological nexus between the posterior eye and the rest of the CNS tissues remains unexplored. Here, studying immune responses to herpes simplex virus in the brain, we observed that intravitreal immunization protects mice against intracranial viral challenge. This protection extended to bacteria and even tumours, allowing therapeutic immune responses against glioblastoma through intravitreal immunization. We further show that the anterior and posterior compartments of the eye have distinct lymphatic drainage systems, with the latter draining to the deep cervical lymph nodes through lymphatic vasculature in the optic nerve sheath. This posterior lymphatic drainage, like that of meningeal lymphatics, could be modulated by the lymphatic stimulator VEGFC. Conversely, we show that inhibition of lymphatic signalling on the optic nerve could overcome a major limitation in gene therapy by diminishing the immune response to adeno-associated virus and ensuring continued efficacy after multiple doses. These results reveal a shared lymphatic circuit able to mount a unified immune response between the posterior eye and the brain, highlighting an understudied immunological feature of the eye and opening up the potential for new therapeutic strategies in ocular and CNS diseases.
Topics: Animals; Female; Humans; Male; Mice; Rabbits; Bacteria; Brain; Dependovirus; Eye; Glioblastoma; Herpesvirus 2, Human; Intravitreal Injections; Lymphatic System; Lymphatic Vessels; Macaca mulatta; Meninges; Optic Nerve; Swine; Zebrafish; Vascular Endothelial Growth Factor C
PubMed: 38418880
DOI: 10.1038/s41586-024-07130-8 -
Progress in Brain Research 2024The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical... (Review)
Review
The dura was first described in ancient Egypt. Hippocrates insisted that it should be protected and not penetrated. Celsus proposed an association between clinical findings and meningeal damage. Galen proposed that the dura was attached only at the sutures, and he was the first to describe the pia in humans. In the Middle Ages, new interest in the management of meningeal injuries arose, with renewed interest in relating clinical changes to intracranial injuries. These associations were neither consistent nor accurate. The Renaissance brought little change. It was in the 18th century that it became clear that the indication for opening the cranium following trauma was to relieve pressure from hematomas. Moreover, the important clinical findings on which to base an indication for intervention were changes in the level of consciousness.
Topics: Humans; Meninges; History, Ancient; History, 19th Century; History, 18th Century; History, 17th Century; History, Medieval; History, 16th Century; History, 15th Century; History, 20th Century
PubMed: 38705713
DOI: 10.1016/bs.pbr.2024.02.020 -
The New England Journal of Medicine Oct 2023
Topics: Humans; Antitubercular Agents; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant
PubMed: 37819958
DOI: 10.1056/NEJMe2310262 -
The Journal of Experimental Medicine Jul 2023The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in...
The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer's disease, impaired meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins in the CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, the mechanisms underlying this decline remain elusive. Here, we demonstrate that age-related alterations in meningeal immunity underlie this lymphatic impairment. Single-cell RNA sequencing of meningeal lymphatic endothelial cells from aged mice revealed their response to IFNγ, which was increased in the aged meninges due to T cell accumulation. Chronic elevation of meningeal IFNγ in young mice via AAV-mediated overexpression attenuated CSF drainage-comparable to the deficits observed in aged mice. Therapeutically, IFNγ neutralization alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable approach to normalize CSF drainage and alleviate the neurological deficits associated with impaired waste removal.
Topics: Mice; Animals; Endothelial Cells; Central Nervous System; Meninges; Lymphatic Vessels; Alzheimer Disease; Lymphatic System; Brain
PubMed: 37027179
DOI: 10.1084/jem.20221929 -
Journal of Neurology Dec 2023There are limited data on HHV-7 meningitis and this systematic review used electronic search to gather pieces of evidence regarding its characteristics. Nine articles... (Review)
Review
There are limited data on HHV-7 meningitis and this systematic review used electronic search to gather pieces of evidence regarding its characteristics. Nine articles were included which three were case reports and the rest of the articles were retrospective studies. Altogether, 32 cases were described in the literature that 13 were females and 26 were aged less than 16 years old. The HHV-7 meningitis has been reported in any season, especially in winter. It affected both immunocompetent and immunocompromised individuals and mostly presented with fever and headache, however rash and seizure have also been documented. The CSF analysis in general showed an elevated range of cell count with lymphocytic predominance and normal to slightly elevated protein levels. Thirteen patients did not receive treatment for HHV-7 meningitis and full recovery was gained in the majority of cases after about 10 days. This review summarizes characteristics of HHV-7 meningitis in the literature, and yet epidemiological studies are needed to shed more light which eventually could be helpful for the diagnosis and management of this disease.
Topics: Female; Humans; Adolescent; Male; Herpesvirus 7, Human; Retrospective Studies; Meningitis; Seizures
PubMed: 37620518
DOI: 10.1007/s00415-023-11950-5 -
Current Pain and Headache Reports Mar 2024While primary headaches like migraines or cluster headaches are prevalent and often debilitating, it's the secondary headaches-those resulting from underlying... (Review)
Review
PURPOSE OF REVIEW
While primary headaches like migraines or cluster headaches are prevalent and often debilitating, it's the secondary headaches-those resulting from underlying pathologies-that can be particularly ominous. This article delves into the sinister causes of headaches, underscoring the importance of a meticulous clinical approach, especially when presented with red flags.
RECENT FINDINGS
Headaches, one of the most common complaints in clinical practice, span a spectrum from benign tension-type episodes to harbingers of life-threatening conditions. For the seasoned physician, differentiating between these extremes is paramount. Headache etiologies covered in this article will include subarachnoid hemorrhage (SAH), cervical artery dissection, cerebral venous thrombosis, meningitis, obstructive hydrocephalus, and brain tumor.
Topics: Humans; Headache; Migraine Disorders; Cerebrovascular Disorders; Brain Neoplasms; Meningitis
PubMed: 38091239
DOI: 10.1007/s11916-023-01202-6