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Journal of Translational Medicine Jun 2024Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity,...
BACKGROUND
Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy.
METHODS
Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL).
RESULTS
Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM.
CONCLUSIONS
This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.
Topics: Humans; Prognosis; Child; Encephalitis; Child, Preschool; Meningitis, Bacterial; Male; Female; Metagenomics; Infant; High-Throughput Nucleotide Sequencing; RNA
PubMed: 38902725
DOI: 10.1186/s12967-024-05370-w -
Acta Medica Okayama Jun 2024Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes...
Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.
Topics: Humans; Male; Meningioma; Hematoma, Subdural, Chronic; Adult; Meningeal Neoplasms; Diagnosis, Differential; Tomography, X-Ray Computed; Magnetic Resonance Imaging
PubMed: 38902217
DOI: 10.18926/AMO/67204 -
Journal of Nippon Medical School =... Jun 2024Sellar reconstruction is important for preventing cerebrospinal fluid (CSF) leakage after transsphenoidal pituitary surgery. This report describes how, despite standard...
Sellar reconstruction is important for preventing cerebrospinal fluid (CSF) leakage after transsphenoidal pituitary surgery. This report describes how, despite standard sellar reconstruction, CSF exudation resulted from dural thinning at the anterior skull base, outside the intrasellar area manipulated during pituitary tumor resection. A 76-year-old man underwent endoscopic transsphenoidal surgery for a pituitary tumor extending toward the anterior skull base. After opening the sellar floor, intractable bleeding from the anterior intercavernous sinus occurred during bone removal at the anterior skull base. Pseudocapsule-based extracapsular resection was completed after stopping the bleeding. On the 10th postoperative day, the patient developed CSF rhinorrhea complicated by marked pneumocephalus, and emergency endoscopic repair of the CSF leak was performed. CSF leakage originated from the thinned dura at the anterior skull base located outside the intrasellar area manipulated during tumor resection. The thinned dural area at the anterior skull base coincided with the site of intractable bleeding of the anterior intercavernous sinus during bone removal in tumor resection. The thinned anterior skull base dura was covered with fascia, overlaid with fat, and closed with the nasoseptal flap. Endoscopic CSF leak repair was successful. Severe damage to the anterior intercavernous sinus can cause extensive exposure of the single-layered inner meningeal dura, where thinning might result in CSF exudation. Therefore, use of autologous tissues to cover and reinforce the severely damaged area of the anterior intercavernous sinus might help prevent postoperative CSF exudation.
PubMed: 38897950
DOI: 10.1272/jnms.JNMS.2025_92-102 -
Vaccine Jun 2024Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths...
Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri Meningo (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri Meningo vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh.
PubMed: 38897895
DOI: 10.1016/j.vaccine.2024.06.030 -
Revista Espanola de Quimioterapia :... Jun 2024
PubMed: 38896776
DOI: 10.37201/req/139.2023 -
Revista Brasileira de Epidemiologia =... 2024To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.
OBJECTIVE
To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.
METHODS
Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density.
RESULTS
182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted.
CONCLUSION
A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.
Topics: Brazil; Humans; Prevalence; Adult; Child; Infant; Meningitis; Adolescent; Middle Aged; Child, Preschool; Young Adult; Male; Female; Spatio-Temporal Analysis; Public Health; Age Distribution; Time Factors; Infant, Newborn; Meningitis, Bacterial
PubMed: 38896651
DOI: 10.1590/1980-549720240031 -
Journal of Veterinary Internal Medicine Jun 2024Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects...
BACKGROUND
Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life.
HYPOTHESIS/OBJECTIVES
Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol.
ANIMALS
Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019). Twenty of 44 were treated with the 6-month protocol and 24/44 with the 6-week protocol.
METHODS
Prospective, randomized trial with 12-month follow-up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling.
RESULTS
All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6-month protocol and 9/24 (38%) of the 6-week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40-4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61-3.48; P = 0.40).
CONCLUSIONS AND CLINICAL IMPORTANCE
"Short" 6-week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.
PubMed: 38895927
DOI: 10.1111/jvim.17130 -
SAGE Open Medical Case Reports 2024Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with...
Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with polycythemia vera. Following in 2018, he experienced an unknown-cause fever and headache. To establish the source of the symptoms, a magnetic resonance imaging scan of the brain was performed, which indicated meningeal and gyral-leptomeningeal thickening and several localized T2 hyperintense lesions measuring up to 10 × 14 mm in diameter. was then cultivated from cerebrospinal fluid. Serum IgM antibodies against West Nile Virus were positive. After 8 weeks of treatment with amphotericin B and fluconazole, the overall condition improved, and the cerebrospinal fluid control culture became negative. The symptoms returned shortly after discontinuing antifungal therapy, necessitating the reintroduction of fluconazole. Currently, the patient is stable and responding positively to ruxolitinib. Here, it is demonstrated how a patient with polycythemia vera due to immunological weakness might develop disseminated cryptococcosis of the brain after West Nile virus infection.
PubMed: 38895656
DOI: 10.1177/2050313X241262145 -
BioRxiv : the Preprint Server For... Jun 2024Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low...
Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) - an aging byproduct - in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared RBCs accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treating these hemorrhagic brain injury models with this ultrasound protocol reduced neuroinflammatory and neurocytotoxic profiles, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. RBC clearance efficacy was blocked by mechanosensitive channel antagonism and was effective when applied in anesthetized subjects, indicating a mechanosensitive channel mediated mechanism that does not depend on sensory stimulation or a specific neural activity pattern. Notably, this protocol qualifies for an FDA non-significant risk designation given its low intensity, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol clears hemorrhage and other harmful substances from the brain via the meningeal lymphatic system, potentially offering a novel therapeutic tool for varied neurologic disorders.
PubMed: 38895304
DOI: 10.1101/2024.06.02.597001 -
Cureus May 2024Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion,...
Moyamoya angiopathy is a rare cerebrovascular condition characterized by insufficient cerebral blood flow resulting from arterial vessel narrowing or occlusion, potentially leading to cerebral ischemia due to inadequate oxygen and nutrient supply to the brain tissue. The development of collateral vessels in stenotic regions, inherently fragile and prone to rupture, may further precipitate intracerebral hemorrhage. Alongside focal neurological symptoms, the common clinical presentations of Moyamoya angiopathy encompass headaches, dizziness, cognitive impairments, seizures, and involuntary movements. When associated with an underlying systemic illness, including Down Syndrome, cranial radiation, neurofibromatosis type 1, or meningitis, the condition is termed Moyamoya syndrome; whereas when idiopathic and a genetic mutation are identified, it is referred to as Moyamoya disease. In this report, we present a case of the rare Moyamoya syndrome, which was attributed to syphilis and HIV infection and was identified during an investigation into the etiology of ischemic stroke in a young patient.
PubMed: 38894803
DOI: 10.7759/cureus.60579