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Continuum (Minneapolis, Minn.) Oct 2018While acute bacterial meningitis is becoming less common in developed countries because of the widespread use of vaccines against Streptococcus pneumoniae, Neisseria... (Review)
Review
PURPOSE OF REVIEW
While acute bacterial meningitis is becoming less common in developed countries because of the widespread use of vaccines against Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae, bacterial meningitis still occurs worldwide, with peak incidence in young children and the elderly. Bacterial meningitis is usually lethal unless appropriate antibiotics that cross the blood-brain barrier are given. Clinical suspicion of bacterial meningitis begins when patients present with the abrupt onset of fever, headache, and meningismus.
RECENT FINDINGS
New technologies are being developed for more rapid identification of the bacterial species causing meningitis. When appropriate, administration of adjunctive dexamethasone with the antibiotics often lessens neurologic sequelae in survivors, which may include aphasia, ataxia, paresis, hearing loss, and cognitive impairment.
SUMMARY
Confirmation of the diagnosis of bacterial meningitis comes mainly from examination and culture of CSF obtained from a lumbar puncture. Typically, the CSF shows an elevated neutrophil count, elevated protein, depressed glucose, positive Gram stain, and growth of the bacteria on appropriate culture media. Antibiotic sensitivities of the bacteria determine the appropriate antibiotics, although an educated guess of the best antibiotics to be given promptly must be made until the antibiotic sensitivities return, usually in a few days.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Middle Aged; Young Adult
PubMed: 30273239
DOI: 10.1212/CON.0000000000000660 -
Neurologic Clinics Feb 2022Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of... (Review)
Review
Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of inflammation on tissue pathology or by cerebrocpinal fluid (CSF) analysis showing pleocytosis or intrathecal antibody synthesis. Clinicians evaluating undifferentiated meningitis or encephalitis should simultaneously consider autoimmune, infectious, and neoplastic causes, using patient risk factors, clinical syndrome, and diagnostic results including CSF and MRI findings to narrow the differential diagnosis. If an autoimmune cause is favored, an important early diagnostic question is whether a specific neural autoantibody is likely to be identified.
Topics: Autoantibodies; Brain; Encephalitis; Humans; Magnetic Resonance Imaging; Meningitis
PubMed: 34798977
DOI: 10.1016/j.ncl.2021.08.007 -
Continuum (Minneapolis, Minn.) Oct 2018This article describes the clinical presentation, diagnostic approach (including the use of novel diagnostic platforms), and treatment of select infectious and... (Review)
Review
PURPOSE OF REVIEW
This article describes the clinical presentation, diagnostic approach (including the use of novel diagnostic platforms), and treatment of select infectious and noninfectious etiologies of chronic meningitis.
RECENT FINDINGS
Identification of the etiology of chronic meningitis remains challenging, with no cause identified in at least one-third of cases. Often, several serologic, CSF, and neuroimaging studies are indicated, although novel diagnostic platforms including metagenomic deep sequencing may hold promise for identifying organisms. Infectious etiologies are more common in those at risk for disseminated disease, specifically those who are immunocompromised because of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), transplantation, or immunosuppressant medications. An important step in identifying the etiology of chronic meningitis is assembling a multidisciplinary team of individuals, including those with specialized expertise in ophthalmology, dermatology, rheumatology, and infectious diseases, to provide guidance regarding diagnostic procedures.
SUMMARY
Chronic meningitis is defined as inflammation involving the meninges that lasts at least 4 weeks and is associated with a CSF pleocytosis. Chronic meningitis has numerous possible infectious and noninfectious etiologies, making it challenging to definitively diagnose patients. Therefore, a multifaceted approach that combines history, physical examination, neuroimaging, and laboratory analysis, including novel diagnostic platforms, is needed. This article focuses on key aspects of the evaluation of and approach to patients with chronic meningitis. Specific infectious etiologies and differential diagnoses of subacute and chronic meningitis, including noninfectious etiologies, are addressed.
Topics: Chronic Disease; Humans; Meningitis
PubMed: 30273241
DOI: 10.1212/CON.0000000000000664 -
Revue Neurologique 2019Aseptic meningitis is defined as meningeal inflammation - i.e. cerebrospinal fluid (CSF) pleocytosis≥5 cells/mm - not related to an infectious process. Etiologies... (Review)
Review
Aseptic meningitis is defined as meningeal inflammation - i.e. cerebrospinal fluid (CSF) pleocytosis≥5 cells/mm - not related to an infectious process. Etiologies of aseptic meningitis can be classified in three main groups: (i) systemic diseases with meningeal involvement, which include sarcoidosis, Behçet's disease, Sjögren's syndrome, systemic lupus erythematosus and granulomatosis with polyangiitis; (ii) drug-induced aseptic meningitis, mostly reported with non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (sulfamides, penicillins), intravenous immunoglobulin, and monoclonal antibodies; (iii) neoplastic meningitis, either related to solid cancer metastasis (breast cancer, lung cancer, melanoma) or malignant hemopathy (lymphoma, leukemia). Most series in the literature included groups of meningitis that are not stricto sensu aseptic, but should rather be included in the differential diagnosis: (i) infectious meningitis related to virus, parasites, fungi, or fastidious bacteria that require specific diagnostic investigations; (ii) bacterial meningitis with sterile CSF due to previous antibiotic administration, and (iii) parameningeal infections associated with meningeal reaction. Despite progress in microbiological diagnosis (including PCR, and next generation sequencing), and identification of a growing panel of autoimmune or paraneoplastic neurological syndromes, up to two thirds of aseptic meningitis cases are of unknown etiology, finally labeled as 'idiopathic'. Description of new entities, such as the syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) may decrease the proportion of idiopathic aseptic meningitis. This state-of-the-art review summarizes the characteristics of main causes of aseptic meningitis.
Topics: Humans; Meningitis, Aseptic
PubMed: 31375286
DOI: 10.1016/j.neurol.2019.07.005 -
Nature Mar 2023The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. Bacterial meningitis causes life-threatening infections of the...
The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year. How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8 nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis.
Topics: Humans; Brain; Calcitonin Gene-Related Peptide; Meninges; Neuroimmunomodulation; Pain; NAV1.8 Voltage-Gated Sodium Channel; Meningitis, Bacterial; Streptococcus agalactiae; Streptococcus pneumoniae; Nociceptors; Receptor Activity-Modifying Protein 1; Macrophages
PubMed: 36859544
DOI: 10.1038/s41586-023-05753-x -
Nature Jul 2015One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous...
One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.
Topics: Animals; Central Nervous System; Cranial Sinuses; Female; Humans; Immune Tolerance; Immunologic Surveillance; Lymphatic Vessels; Male; Meninges; Mice, Inbred C57BL; T-Lymphocytes
PubMed: 26030524
DOI: 10.1038/nature14432 -
Seminars in Neurology Dec 2015Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid... (Review)
Review
Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid examination. In contrast, encephalitis refers to inflammation of the brain parenchyma itself and often results in focal neurologic deficits or seizures. In this article, the authors review the differential diagnosis of meningitis and encephalitis, with an emphasis on infectious etiologies. The recommended practical clinical approach focuses on early high-yield diagnostic testing and empiric antimicrobial administration, given the high morbidity associated with these diseases and the time-sensitive nature of treatment initiation. If the initial workup does not yield a diagnosis, further etiology-specific testing based upon risk factors and clinical characteristics should be pursued. Effective treatment is available for many causes of meningitis and encephalitis, and when possible should address both the primary disease process as well as potential complications.
Topics: Diagnosis, Differential; Encephalitis; Humans; Meningitis
PubMed: 26595861
DOI: 10.1055/s-0035-1564686 -
Archives of Disease in Childhood.... Feb 2020Meningitis is a critical diagnosis not to miss in children presenting with fever. Since the early 20th century, classical clinical signs have been used to aid the... (Review)
Review
Meningitis is a critical diagnosis not to miss in children presenting with fever. Since the early 20th century, classical clinical signs have been used to aid the diagnosis of meningitis. These classical signs are nuchal rigidity, Kernig's sign and Brudzinski's sign. Each of these relies on the principle that stretching the inflamed meningeal membranes causes clinically detectable irritation. Several primary studies have quantified the diagnostic performance of clinical examination in detecting meningitis in children. The results of these studies vary significantly due to methodological differences, clinical heterogeneity and interobserver variability. However, their findings demonstrate that positive meningitic signs increase the likelihood of a diagnosis of meningitis, and the absence of meningitic signs reduces this probability. These signs have greatest utility when combined with other features in the history and examination to contribute to a comprehensive clinical assessment.
Topics: Child; Diagnosis, Differential; Humans; Medical History Taking; Meningitis; Physical Examination
PubMed: 30692129
DOI: 10.1136/archdischild-2018-315428 -
Science (New York, N.Y.) Jan 2023The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that...
The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.
Topics: Animals; Humans; Mice; Dura Mater; Endothelium; Subarachnoid Space; Epithelium; Brain; Cerebrospinal Fluid
PubMed: 36603070
DOI: 10.1126/science.adc8810 -
Trends in Molecular Medicine Jun 2018The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping... (Review)
Review
The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions. The location and activation state of meningeal immune cells can profoundly influence CNS homeostasis and contribute to neurological disorders, but these cells are also well equipped to protect the CNS from pathogens. In this review, we discuss advances in our understanding of the meningeal immune repertoire and provide insights into how this CNS barrier operates immunologically under conditions ranging from neurocognition to inflammatory diseases.
Topics: Animals; Central Nervous System; Disease Susceptibility; Homeostasis; Humans; Immune System; Immunity; Meninges; Meningitis
PubMed: 29731353
DOI: 10.1016/j.molmed.2018.04.003