Enhancing the cytological features and diagnostic significance of cerebrospinal fluid in bacterial meningitis.

Objective: The objective of this study was to investigate the cytological features and diagnostic significance of cerebrospinal fluid (CSF) in bacterial meningitis (BM). Material and Methods: Patients diagnosed with BM at the First Affiliated Hospital of Nanchang University Hospital between August 2021 and April 2022 were enrolled. Clinical, cranial imaging, CSF-next-generation sequencing, CSF examination, and CSF cytology data were retrospectively analyzed. CSF cytology samples were prepared using a CSF cell pelletizer (precipitation method) and stained using the May-Grunwald-Glemsa (MGG) method. The χ2 test was employed to compare the positive rate of routine CSF count and CSF cytology. Results: Eight patients (four males and four females), aged 41-67 years, were included. Among them, two patients had undergone brain surgery within the past 4 months, one patient had an 8-year history of otitis media, and two patients had a history of sudden toothache. Clinical manifestations included fever, headache, sudden disturbance of consciousness, and neck stiffness. CSF cytology revealed abnormal inflammatory changes dominated by neutrophils in seven patients. Routine CSF cell counts exceeded 100/uL in only four cases, indicating a higher positive rate of CSF cytology for detecting CSF inflammatory reactions compared to routine cell count. Conclusion: Comparative detection of bacteria through the observation of CSF cytology inflammatory status in BM patients are more useful for diagnosing BM than routine CSF counts.

From cytokines to chemokines: Understanding inflammatory signaling in bacterial meningitis.

Bacterial meningitis is a serious central nervous system (CNS) infection, claiming millions of human lives annually around the globe. The deadly infection involves severe inflammation of the protective sheath of the brain, i.e., meninges, and sometimes also consists of the brain tissue, called meningoencephalitis. Several inflammatory pathways involved in the pathogenesis of meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, Haemophilus influenzae, Mycobacterium tuberculosis, Streptococcus suis, etc. are mentioned in the scientific literature. Many in-vitro and in-vivo analyses have shown that after the disruption of the blood-brain barrier (BBB), these pathogens trigger several inflammatory pathways including Toll-Like Receptor (TLR) signaling in response to Pathogen-Associated Molecular Patterns (PAMPs), Nucleotide oligomerization domain (NOD)-like receptor-mediated signaling, pneumolysin related signaling, NF-κB signaling and many other pathways that lead to pro-inflammatory cascade and subsequent cytokine release including interleukine (IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) along with other mediators, leading to neuroinflammation. The activation of another protein complex, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome, also takes place resulting in the maturation and release of IL-1ß and IL-18, hence potentiating neuroinflammation. This review aims to outline the inflammatory signaling pathways associated with the pathogenesis of bacterial meningitis leading to extensive pathological changes in neurons, astrocytes, oligodendrocytes, and other central nervous system cells.

Glioma grade and post-neurosurgical meningitis risk.

BACKGROUND: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. METHODS: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). RESULTS: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. CONCLUSIONS: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.

Blood culture bottles for culturing cerebrospinal fluid in cases of bacterial meningitis caused by Enterococcus faecalis: A case report.

Pathogen identification is essential for the treatment of bacterial meningitis. However, cerebrospinal fluid (CSF) culture tests are often negative when antimicrobial agents are administered before CSF is collected. Therefore, it is necessary to improve the culturing process for such samples. Here, we report a case of bacterial meningitis where the causative bacteria were detected by inoculating that patient's CSF samples into blood culture bottles. A 52-year-old man developed a fever and headache after undergoing transnasal transsphenoidal surgery for a nonfunctioning pituitary neuroendocrine tumor. He was suspected of having a wound infection, for which he was treated with cefozopran and vancomycin. A CSF test was also performed, owing to persistent fever, and bacterial meningitis was suspected. Although conventional CSF culture tests were negative, CSF cultures using blood culture bottles detected Enterococcus faecalis. The antimicrobial agents were therefore changed to ampicillin and gentamicin, after which the patient's meningitis improved. The blood culture bottles used contained adsorbed polymer beads with antimicrobial neutralizing properties, which likely contributed to the isolation of the bacteria. In addition to conventional cultures, ones done in blood culture bottles may be useful for diagnosing bacterial meningitis via CSF samples-particularly in cases where antimicrobial agents have already been administered.

Otitis in patients with Community-Acquired Bacterial Meningitis: A Nationwide Prospective Cohort Study.

BACKGROUND: Otitis is commonly associated with community-acquired bacterial meningitis but role of ear surgery as treatment is debated. In this study, we investigated the impact of otitis and ear surgery on outcome of adults with community-acquired bacterial meningitis. METHODS: We analyzed episodes of adults with community-acquired bacterial meningitis from a nationwide prospective cohort study in the Netherlands, between March 2006 to July 2021. RESULTS: A total of 2,548 episodes of community-acquired bacterial meningitis were evaluated. Otitis was present in 696 episodes (27%). In these patients the primary causative pathogen was Streptococcus pneumoniae (615 of 696 [88%]), followed by Streptococcus pyogenes (5%) and Haemophilus influenzae (4%). In 519 of 632 otitis episodes (82%) an ear-nose-throat specialist was consulted, and surgery was performed in 287 of 519 (55%). The types of surgery performed were myringotomy with ventilation tube insertion in 110 of 287 episodes (38%), mastoidectomy in 103 of 287 (36%) and myringotomy alone in 74 of 287 (26%). Unfavorable outcome occurred in 210 of 696 episodes (30%) and in 65 of 696 episodes was fatal (9%). Otitis was associated with a favorable outcome in a multivariable analysis (odds ratio 0.74; 95% CI 0.59-0.92; p =0.008). There was no association between outcome and ear surgery. CONCLUSIONS: Otitis is a common focus of infection in community-acquired bacterial meningitis in adults, with S. pneumoniae being the most common causative pathogen. Presence of otitis is associated with a favorable outcome. Ear surgery's impact on the outcome of otogenic meningitis patients remains uncertain.

A Reduction in the Number of Hospitalized Cases of Acute Meningitis during the COVID-19 Pandemic in Japan.

Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the prevalence of acute meningitis before and during the COVID-19 pandemic in Japan. Methods We retrospectively reviewed the Japanese nationwide administrative medical payment system database, Diagnosis Procedure Combination (DPC), from 2016 to 2022. A total of 547 hospitals consistently and seamlessly offered DPC data during this period. The study period was divided into the following three periods: April 2016 to March 2018 (fiscal years 2016-2017), April 2018-March 2020 (2018-2019), and April 2020-March 2022 (2020-2021). Results Among the 28,161,806 patients hospitalized during the study period, 28,399 were hospitalized for acute meningitis: 16,678 for viral/aseptic type, 6,189 for bacterial type, 655 for fungal type, 429 for tuberculous, 2,310 for carcinomatous type, and 2,138 for other or unknown types of meningitis. A significant decrease during the pandemic was confirmed in viral (n=7,032, n=5,775, and n=3,871 in each period; p<0.0001) and bacterial meningitis (n=2,291, n=2,239, and n=1,659; p<0.0001) cases. Meanwhile, no decrease was observed in fungal meningitis (n=212, n=246, and n=197; p=0.056) or carcinomatous meningitis (n=781, n=795, and n=734; p=0.27). The decrease in the number of tuberculous meningitis cases was equivocal (n=166, n=146, and n=117; p=0.014). The decrease during the pandemic was more remarkable in younger populations aged <50 years than in older populations, both for viral and bacterial meningitis. Conclusion The number of hospitalized cases of acute meningitis clearly decreased during the COVID-19 pandemic, especially for viral and bacterial meningitis in younger populations aged <50 years.

An unusual imaging presentation of pediatric bacterial meningoencephalitis: a case-report study.

Background: Bacterial meningoencephalitis is a serious infection affecting the brain and its surrounding membranes. While imaging studies play a crucial role in diagnosing this condition, the typical radiological findings are well-documented. However, this case report describes an unusual imaging presentation that deviates from the expected patterns, emphasizing the need for awareness of such variations. Case presentation: A 7-year-old female with no prior medical history was referred to our hospital with fever, seizure, and loss of Consciousness. She had mild flu a week before admission. The duration of seizure episodes were 2-3 min, with tonic-clonic uncontrollable jerky movements. Brudzinski and Kernig signs were positive and plantar reflex was upward bilaterally in the physical examination. The computed tomography (CT) scan showed brain ventriculomegaly/hydrocephalus, and MRI findings indicated multiple foci located at cerebellum, basal ganglia, and thalamus alongside intensely restricted diffusion of the layering debris, suggesting pyogenic ventriculitis. Cerebrospinal fluid (CSF) analysis showed severe hypoglycorrhachia, despite non-significant increase of protein. The patient was undergone antibiotic therapy with ceftriaxone, vancomycin and rifampin, resulting in normalization of CSF values. Conclusion: This case report highlights the importance of recognizing and interpreting unusual imaging presentations of bacterial meningoencephalitis in paediatric patients. It emphasizes the need for a comprehensive diagnostic approach, including clinical evaluation, laboratory tests, and imaging studies, to ensure accurate diagnosis and appropriate management of this potentially life-threatening condition. Further research and awareness of atypical imaging findings are warranted to enhance our understanding and improve patient outcomes.

Case Report: Bacterial meningitis due to cerebrospinal fluid leakage following unilateral biportal endoscopic spinal surgery: a cautionary tale.

Unilateral biportal endoscopic spinal surgery (UBE) is a rapidly growing surgical method and has attracted much interest recently. The most common complication of this technique is cerebrospinal fluid (CSF) leakage due to intraoperative dural tears. There have been no reports of bacterial meningitis due to dural tears in UBE surgery and its treatment and prevention. We reported a 47 year-old man with CSF due to an intraoperative dural tear. A drainage tube was routinely placed and removed on the fourth day after surgery, resulting in fever and headache on the fifith postoperative day. Blood and CSF cultures showed Klebsiella pneumoniae infection, and with lumbar drainage and appropriate antibiotics based on sensitivity tests, the patient's fever and headache were effectively relieved. This case report suggests the importance of prolonged drainage tube placement, adequate drainage, careful intraoperative separation to avoid dural tears, and effective sensitive antibiotic therapy.

Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis.

PURPOSE: There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. METHODS: A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. RESULTS: The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). CONCLUSION: Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.

Streptococcus suis meningitis: An emerging zoonotic disease in Brazil

ABSTRACT Streptococcus suis has been widely reported as a pathogen in animals, especially pigs. In terms of human health implications, it has been characterized as a zoonosis associated with the consumption of pork products and occupational exposure, particularly in Southeast Asian countries. Here, we present a rare case of human S. suis infection in Brazil, diagnosed in an older adult swine farmer, a small rural producer residing in the semi-arid region of Bahia, Brazil.

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.

Cytokine profile in patients with acute bacterial meningitis.

BACKGROUND: Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis. METHODS: The study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used. RESULTS: In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis. CONCLUSION: Among patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.

Meningitis after elective intracranial surgery: a systematic review and meta-analysis of prevalence.

Meningitis is a potential complication of elective intracranial surgery (EIS). The prevalence of meningitis after EIS varies greatly in the literature. The objective of this study was to estimate the overall pooled prevalence of meningitis following EIS. Four databases (PubMed, Scopus, Web of Science, and Embase) were searched to identify relevant studies. Meta-analyses of proportions were used to combine data. Cochran's Q and I2 statistics were used to assess and quantify heterogeneity. Additionally, several subgroup analyses were conducted to investigate the source of heterogeneity and examine differences in the prevalence based on variables such as geographical regions, income level, and meningitis type. The meta-analysis included 83 studies (30 959 patients) from 26 countries. The overall pooled prevalence of meningitis after EIS was 1.6% (95% CI 1.1-2.1), with high heterogeneity present (I2 = 88%). The pooled prevalence in low- to middle-income countries and high-income countries was 2.7% (95% CI 1.6-4.1) and 1.2% (95% CI 0.8-1.7), respectively. Studies that reported only aseptic meningitis had a pooled prevalence of 3.2% (95% CI 1.3-5.8). The pooled prevalence was 2.8% (95% CI 1.5-4.5) in studies that reported only bacterial meningitis. Similar prevalence rates of meningitis were observed in the subgroups of tumor resection, microvascular decompression, and aneurysm clipping. Meningitis is a rare but not exceptional complication following EIS, with an estimated prevalence of 1.6%.

Protocol for Evaluation and Management of Hearing Loss After Meningitis.

Bacterial meningitis is the most common cause of post-natal acquired hearing loss in children. Although cochlear implantation helps in improving the hearing in these patients, the fibrosis and ossification of the cochlear lumen that occurs as a result of bacterial meningitis, limits the chances of successful implantation. In developing countries like India, the reduced awareness, limited resources, and financial constraints warrant judicial use of radiological and audiological tests to increase the rate of successful cochlear implantation. The present paper is a review of the literature and a proposed protocol for follow-up of post-meningitis patients to help clinicians diagnose and hence, intervene early when profound hearing loss occurs. Every patient who has had an episode of bacterial meningitis must be followed up for atleast 2 years for possible hearing loss with frequent audiological and radiological evaluation, as required. Cochlear implantation must be done as early as possible when profound hearing loss is detected.

Post-neurosurgical Nocardia meningoventriculitis: a case report and review of the literature.

The genus Nocardia consists of a group of gram-positive environmental bacteria. They typically cause lung and brain infections in immunocompromised patients, even though one out of three infected patients have a normally functioning immune system. Being a ubiquitous microorganism, in some cases Nocardia has been associated with nosocomial acquired infections and surgical procedures. A review of the literature in this field follows the case report. A 47-year-old woman underwent an endoscopic third ventriculostomy and a left retro-sigmoid craniotomy for a schwannoma removal. Meningeal symptoms began a week later, in association with C reactive protein rise and leukocytosis. Cerebrospinal fluid (CSF) examination was clear with hypoglycorrhachia, hyperprotidorrachia and polymorphonuclear cells. Cultural exam was negative. At the brain magnetic resonance imaging (MRI) purulent material was described in the occipital ventricular horns. Empirical broad spectrum antibiotic therapy was given for 31 days until the brain MRI showed a resolution of the infection. Ten days later, the patient was admitted to the hospital because of new meningeal symptoms. Cerebrospinal fluid culture and Polymerase-chain reaction (PCR) Multiplex for the most important meningitis viruses and bacteria tested negative. A broad-spectrum antibiotic therapy was started with no benefit; thus, a broad-spectrum antifungal therapy was added with little success on clinical status. Meanwhile, a 16s and 18s rRNA PCR was executed on a previous Cerebrospinal fluid with negative results, excluding bacterial and fungal infections. For this reason, all the therapies were stopped. After a few days, high fever and meningeal signs reappeared. The brain MRI showed a meningoventriculitis. An Ommaya catheter with reservoir was inserted and the drawn CSF resulted in the growth of Nocardia farcinica. Antibiogram-based antibiotic therapy was started with intravenous imipenem and trimethoprim-sulfamethoxazole, showing clinical benefit. The patient was sent home with oral linezolid and amoxicillin/clavulanate for a total of 12 months of therapy. Nocardia rarely causes post-neurosurgical complication in a nosocomial setting. This case shows the difficulty in detecting Nocardia and the importance of the correct microbiological sample and antibiogram-based antibiotic therapy to achieve successful treatment.

Development a prediction model for identifying bacterial meningitis in young infants aged 29-90 days: a retrospective analysis.

BACKGROUND: The early diagnosis and treatment of bacterial meningitis (BM) in young infants was very critical. But, it was difficult to make a definite diagnosis in the early stage due to nonspecific clinical symptoms. Our objectives were to find the risk factors associated with BM and develop a prediction model of BM especially for young infants. METHODS: We retrospectively reviewed the clinical data of young infants with meningitis between January 2011 and December 2020 in Children's Hospital of Soochow University. The independent risk factors of young infants with BM were screened using univariate and multivariate logistic regression analyses. The independent risk factors were used to construct a new scoring model and compared with Bacterial Meningitis Score (BMS) and Meningitis Score for Emergencies (MSE) models. RESULTS: Among the 102 young infants included, there were 44 cases of BM and 58 of aseptic meningitis. Group B Streptococcus (22, 50.0%) and Escherichia coli (14, 31.8%) were the main pathogens of BM in the young infants. Multivariate logistic regression analysis identified procalcitonin (PCT), cerebrospinal fluid (CSF) glucose, CSF protein as independent risk factors for young infants with BM. We assigned one point for CSF glucose ≤ 1.86 mmol/L, two points were assigned for PCT ≥ 3.80 ng/ml and CSF protein ≥ 1269 mg/L. Using the not low risk criterion (score ≥ 1) with our new prediction model, we identified the young infantile BM with 100% (95% CI 91.9%-100%) sensitivity and 60.3% (95% CI 46.4%-72.9%) specificity. Compared with BMS and MSE model, our prediction model had larger area under receiver operating characteristic curve and higher specificity, the differences were statistically significant. CONCLUSION: Our new scoring model for young infants can facilitate early identification of BM and has a better performance than BMS and MSE models.

Mechanical filtration of the cerebrospinal fluid: procedures, systems, and applications.

INTRODUCTION: Mechanical methods aimed at the filtration of the cerebrospinal fluid (CSF) are a group of therapies that have been proposed to treat neurological conditions where pathogens are present in the CSF. Even though the industry of medical devices has not been very active in this field, there is a lack of systematization of the different systems and procedures that can be applied. AREAS COVERED: First, we systematize the classification and definitions of procedures and systems for mechanical filtration of the CSF. Then, we made a literature review in search of clinical or preclinical studies where any system of mechanical CSF clearance was proposed or applied. EXPERT OPINION: We found mechanical filtration of the CSF has been explored in subarachnoid hemorrhage, CNS infections (bacterial, viral, and fungal), meningeal carcinomatosis, multiple sclerosis, autoimmune encephalitis, and polyradiculomyelitis. Brain aging and neurodegenerative diseases are additional potential conditions of interest. While there is some preliminary positive evidence for many of these conditions, more advanced systems, detailed descriptions of procedures, and rigorous validations are needed to make these therapies a reality in the next decades.

Community-acquired Staphylococcus aureus meningitis in adults.

BACKGROUND: Staphylococcus aureus is an uncommon cause of community-acquired bacterial meningitis. We aimed to describe patients with this disease. METHODS: We evaluated clinical characteristics and outcome of adults with community-acquired S. aureus meningitis from prospective nationwide cohort studies from Denmark (2015-2020) and the Netherlands (2006-2021). Whole genome sequencing of S. aureus isolates was performed to evaluate the potential association between clonal complex and clinical characteristics. RESULTS: We evaluated 111 episodes of community-acquired S. aureus meningitis: 65 from Denmark and 46 from the Netherlands. The median age was 66 years (interquartile range [IQR] 50-74) and 43 of 111 patients were female (39%). Concomitant infectious foci were found in 95 of 107 patients (89%), most commonly endocarditis (53 of 109 [49%]) and spondylodiscitis (43 of 109 [39%]). The triad of neck stiffness, altered mental status (Glasgow Coma Scale score <14), and fever was present in only 18 of 108 patients (17%). Surgery was performed in 14 of 33 patients (42%) with spondylodiscitis and 26 of 52 (50%) with endocarditis. A favorable outcome (Glasgow Outcome Scale score 5) occurred in 26 of 111 patients (23%), while 39 (35%) died. The most common bacterial clonal complexes (CC) were CC30 (16 [17%]), CC45 (16 [17%]), CC5 (12 [13%], and CC15 (10 [11%]); no associations between CCs and concomitant foci or outcome were found. CONCLUSIONS: Community-acquired S. aureus meningitis is a severe disease with a high case fatality rate, occurring mainly in patients with concomitant endocarditis or spondylodiscitis.

Oral GSH Exerts a Therapeutic Effect on Experimental Salmonella Meningitis by Protecting BBB Integrity and Inhibiting Salmonella-induced Apoptosis.

Bacterial meningitis (BM) is the main cause of the central nervous system (CNS) infection and continues to be an important cause of mortality and morbidity. Glutathione (GSH), an endogenous tripeptide antioxidant, has been proved to exert crucial role in reducing superoxide radicals, hydroxyl radicals and peroxynitrites. The purpose of this study is to expand the application scope of GSH via exploring its therapeutic effect on BM caused by Salmonella typhimurium SL1344 and then provide a novel approach for the treatment of BM. The results suggested that intragastric administration of GSH could significantly increase median survival and improve experimental autoimmune encephalomyelitis score of BM model mice. However, exogenous GSH did not affect the adhesion, invasion and cytotoxicity of SL1344 to C6, BV2 and primary microglia. Due to the contradiction between the therapeutic and bactericidal effects of GSH, the effect of GSH on blood-brain barrier (BBB) was investigated to explore its action target for the treatment of meningitis. GSH was found to repair the damage of BBB and then prevent the leakage of SL1344 from the brain to the blood circulation. The repaired BBB could also effectively reduce the entry of macrophages and neutrophils into the brain, and significantly reverse the microglia activation induced by SL1344. More importantly, exogenous GSH was proved to reduce mouse brain cell apoptosis by inhibiting the activation of caspase-8 followed by caspase-3, and reversing the up-regulation of ICAD and PARP-1 caused by SL1344.

Vimentin as a potential target for diverse nervous system diseases.

Vimentin is a major type III intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout (GFAP-/-VIM-/-) mice. However, attenuated glial scar formation in post-stroke in GFAP-/- VIM-/- mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIM-/- mice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.