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European Journal of Neurology Jan 2024Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited.
BACKGROUND AND PURPOSE
Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited.
METHODS
This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison.
RESULTS
Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis.
CONCLUSIONS
Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.
Topics: Adult; Humans; Cohort Studies; Meningitis, Viral; Aftercare; Polymerase Chain Reaction; Recurrence; Patient Discharge; Meningitis, Aseptic; Herpesvirus 2, Human; Denmark
PubMed: 37797296
DOI: 10.1111/ene.16081 -
The Journal of Neuroscience : the... Aug 2023Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache...
Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD is also thought to drive the headache phase in migraine by promoting the activation and mechanical sensitization of trigeminal primary afferent nociceptive neurons that innervate the cranial meninges. The factors underlying meningeal nociception in the wake of CSD remain poorly understood but potentially involve the parenchymal release of algesic mediators and damage-associated molecular patterns, particularly ATP. Here, we explored the role of ATP-P2X purinergic receptor signaling in mediating CSD-evoked meningeal afferent activation and mechanical sensitization. Male rats were subjected to a single CSD episode. , extracellular single-unit recording was used to measure meningeal afferent ongoing activity changes. Quantitative mechanical stimuli using a servomotor force-controlled stimulator assessed changes in the afferent's mechanosensitivity. Manipulation of meningeal P2X receptors was achieved via local administration of pharmacological agents. Broad-spectrum P2X receptor inhibition, selective blockade of the P2X7 receptor, and its related Pannexin 1 channel suppressed CSD-evoked afferent mechanical sensitization but did not affect the accompanying afferent activation response. Surprisingly, inhibition of the pronociceptive P2X2/3 receptor did not affect the activation or sensitization of meningeal afferents post-CSD. P2X7 signaling underlying afferent mechanosensitization was localized to the meninges and did not affect CSD susceptibility. We propose that meningeal P2X7 and Pannexin 1 signaling, potentially in meningeal macrophages or neutrophils, mediates the mechanical sensitization of meningeal afferents, which contributes to migraine pain by exacerbating the headache during normally innocuous physical activities. Activation and sensitization of meningeal afferents play a key role in migraine headache, but the underlying mechanisms remain unclear. Here, using a rat model of migraine with aura involving cortical spreading depolarization (CSD), we demonstrate that meningeal purinergic P2X7 signaling and its related Pannexin 1 pore, but not nociceptive P2X2/3 receptors, mediate prolonged meningeal afferent sensitization. Additionally, we show that meningeal P2X signaling does not contribute to the increased afferent ongoing activity in the wake of CSD. Our finding points to meningeal P2X7 signaling as a critical mechanism underlying meningeal nociception in migraine, the presence of distinct mechanisms underlying the activation and sensitization of meningeal afferents in migraine, and highlight the need to target both processes for effective migraine therapy.
Topics: Rats; Male; Animals; Nociceptors; Migraine Disorders; Meninges; Headache; Adenosine Triphosphate
PubMed: 37487740
DOI: 10.1523/JNEUROSCI.0368-23.2023 -
Nature Communications Sep 2023Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal...
Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1 cells located within the arachnoid beneath and separate from E-cadherin arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.
Topics: Female; Animals; Mice; Pia Mater; Neuroinflammatory Diseases; Central Nervous System; Arachnoid; Cadherins; Inflammation; Mice, Transgenic
PubMed: 37730744
DOI: 10.1038/s41467-023-41580-4 -
Pediatric Annals Nov 2023is a new emerging foodborne bacterial pathogen associated with fatal infections such as meningitis, necrotizing enterocolitis, and septicemia in neonates. Powdered...
is a new emerging foodborne bacterial pathogen associated with fatal infections such as meningitis, necrotizing enterocolitis, and septicemia in neonates. Powdered infant formula milk has been recognized as one of the main transmission vehicles and contaminated sources of this pathogen. Educating parents about the importance of hygienic reconstitution of powdered infant formula, storage practices, and hand hygiene is crucial to reducing the risk of this life-threatening infection. The clinician should be aware of the special considerations for antimicrobial treatment selection as well as further necessary evaluation. Here, we report a case of a twin neonate who presented with meningitis and septicemia. .
Topics: Infant; Infant, Newborn; Humans; Cronobacter sakazakii; Infant Formula; Meningitis; Sepsis
PubMed: 37935393
DOI: 10.3928/19382359-20230906-04 -
Frontiers in Public Health 2024The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic...
BACKGROUND
The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability.
METHODS
TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes.
RESULTS
A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus.
CONCLUSION
Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.
Topics: Humans; Adult; Tuberculosis, Meningeal; Ischemic Stroke; Risk Factors; Inflammation; Hydrocephalus
PubMed: 38577289
DOI: 10.3389/fpubh.2024.1362465 -
Journal of Translational Medicine Sep 2023The early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical...
Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study.
BACKGROUND
The early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM.
METHODS
We prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment.
RESULTS
The concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (all P < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770-0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05).
CONCLUSIONS
CSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.
Topics: Humans; Anti-Bacterial Agents; Lipocalin-2; Meningitis, Bacterial; Meningitis, Cryptococcal; Prospective Studies; Tuberculosis, Meningeal
PubMed: 37679727
DOI: 10.1186/s12967-023-04485-w -
Neuron May 2024Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals...
Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.
Topics: Animals; Ischemic Stroke; Mice; Collateral Circulation; Humans; Reperfusion; Meninges; Male; Cerebrovascular Circulation; Mice, Inbred C57BL; Disease Models, Animal; Brain; Thrombectomy
PubMed: 38412858
DOI: 10.1016/j.neuron.2024.01.031 -
Clinical Laboratory Dec 2023Differentiating bacterial and viral meningitis is crucial, and this study explored the potential of mean platelet volume (MPV) as a marker for differentiation.
BACKGROUND
Differentiating bacterial and viral meningitis is crucial, and this study explored the potential of mean platelet volume (MPV) as a marker for differentiation.
METHODS
Blood samples were collected from patients with central nerve system related manifestations, and MPV was tested. Cerebrospinal fluid samples were obtained and bacterial culture and the FilmArray ME panel were performed. The distribution of MPV was compared between groups.
RESULTS
The study included 8 patients in the bacterial meningitis group and 12 patients in the viral meningitis group. The bacterial meningitis group showed a significantly higher median MPV of 10.9 (9.2 - 11.6) fL compared to the viral meningitis group with 8.4 (8.1 - 8.8) fL (p < 0.0001).
CONCLUSIONS
MPV could serve as a diagnostic indicator to differentiate between bacterial and viral meningitis. Larger studies are needed to validate these findings.
Topics: Humans; Mean Platelet Volume; Meningitis, Bacterial; Bacteria; Meningitis, Viral; Meningitis
PubMed: 38084680
DOI: 10.7754/Clin.Lab.2023.230631 -
Cell Aug 2023Channels connecting the skull bone marrow and the meninges have recently been discovered as a path for immune cell and molecule trafficking. In this issue of Cell,...
Channels connecting the skull bone marrow and the meninges have recently been discovered as a path for immune cell and molecule trafficking. In this issue of Cell, Kolabas, Kuemmerle, Perneczky, Förstera, and colleagues characterize these channels in humans and mice, revealing unique features of skull bone marrow and localized activation in human pathology.
Topics: Animals; Humans; Mice; Bone Marrow; Meninges; Skull
PubMed: 37595561
DOI: 10.1016/j.cell.2023.07.025 -
Child's Nervous System : ChNS :... Apr 2024We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available... (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available evidence.
METHODS
DESIGN: Systematic review and meta-analysis.
DATA SOURCES
PubMed, EMBASE, LILACS, and SCOPUS up to 17 February 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized experimental and observational studies were included. The Cochrane methodology was used for systematic reviews.
RESULTS
Twenty-six observational studies and one randomized clinical trial involving 272 patients were included. The risk of bias in both pediatric and neurosurgical studies was high, and the quality of evidence was low (evidence level C). In the pediatric studies, no significant differences in mortality were found between intraventricular antibiotics and only systemic antibiotic [25.4% vs 16.1%, OR = 0.96 (0.42-2.24), P = 0.93]. However, when analyzing the minimum administered doses, we found a lower mortality when a minimum duration of 3 days for intraventricular antibiotics was used compared to only systemic antibiotic [4.3% vs 17%, OR = 0.22 (0.07-0.72), P = 0.01]. In the neurosurgical studies, the use of intraventricular antibiotics in ventriculitis generally results in a mortality of 5% and a morbidity of 25%, which is lower than that in cases where intraventricular antibiotics were not used, with an average mortality of 37.3% and a morbidity of 50%.
CONCLUSION
Considering the low quality of evidence in pediatric and neurosurgical studies, we can conclude with a low level of certainty that intraventricular antibiotics may not significantly impact mortality in neonatal meningitis and ventriculitis. However, reduced mortality was observed in cases treated with a minimum duration of 3 days of intraventricular antibiotic, particularly the multidrug-resistant or treatment-refractory infections. Higher-quality studies are needed to improve the quality of evidence and certainty regarding the use of intraventricular antibiotics for treating neonatal meningitis and ventriculitis.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Cerebral Ventriculitis; Meningitis; Randomized Controlled Trials as Topic
PubMed: 38015250
DOI: 10.1007/s00381-023-06240-4