Central Nervous System Infection Research Articles

Sarcopenia Predicts the Development of Early Adjacent Segment Disease After Transforaminal Lumbar Interbody Fusion.

Predicting the development of adjacent segment disease (ASD) after lumbar spine fusion would help guide preoperative and postoperative therapies to prevent reoperation. We sought to evaluate whether sarcopenia predicts the development of early ASD after transforaminal lumbar interbody fusion (TLIF). Retrospective data were collected from 109 patients who underwent TLIF from 2013 to 2023. Patients older than 18 years who underwent elective posterior midline approach TLIF were included. Patients with prior lumbar instrumented fusions, cases of trauma, central nervous system infection, cancer, or long-construct thoracolumbar deformity corrections and those who lacked sufficient follow-up were excluded. The primary outcome was radiographic ASD development within 3 years of surgery. Psoas volumetric measurements were recorded from the most recent preoperative MRI. Odds ratios were calculated with logistic regression analyses. In 109 patients undergoing elective TLIF, 22 (20.2%) developed ASD within 3 years. Gender, body mass index, and extent of surgery were not associated with ASD development. Multivariate analysis showed left/right psoas cross-sectional area, and psoas:vertebral body ratio (P:VBR) predicted early ASD (P < .0001). Sarcopenia was further categorized as having bilateral P:VBR ≥1 SD below gender mean (T-score -1). Of 18 sarcopenic patients, 15 developed early ASD (83.33%) vs 7 of 91 nonsarcopenic patients (7.69%; P < .0001). Postoperative mismatch between pelvic incidence and lumbar lordosis was predictive of ASD on univariate (P = .0480) but not multivariate analysis. Pelvic tilt and lumbar lordosis postoperatively were not associated with early ASD. Sarcopenia, measured by decreased psoas area and P:VBR, predicts ASD formation within 3 years of surgery. Morphometric analysis of psoas size is a simple tool to identify patients at risk of developing ASD. This information can potentially guide preoperative and postoperative therapies, affect surgical decision making, and effectively counsel patients on risks of reoperation.

Sialic acid and PirB are not required for targeting of neural circuits by neurotropic mammalian orthoreovirus.

Serotype 3 (T3) strains of mammalian orthoreovirus (reovirus) spread to the central nervous system to infect the brain and cause lethal encephalitis in newborn mice. Although reovirus targets several regions in the brain, susceptibility to infection is not uniformly distributed. The neuronal subtypes and anatomic sites targeted throughout the brain are not precisely known. Reovirus binds several attachment factors and entry receptors, including sialic acid (SA)-containing glycans and paired immunoglobulin-like receptor B (PirB). While these receptors are not required for infection of some types of neurons, reovirus engagement of these receptors can influence neuronal infection in certain contexts. To identify patterns of T3 neurotropism, we used microbial identification after passive tissue clearance and hybridization chain reaction to stain reovirus-infected cells throughout intact, optically transparent brains of newborn mice. Three-dimensional reconstructions revealed in detail the sites targeted by reovirus throughout the brain volume, including dense infection of the midbrain and hindbrain. Using reovirus mutants incapable of binding SA and mice lacking PirB expression, we found that neither SA nor PirB is required for the infection of various brain regions. However, SA may confer minor differences in infection that vary by region. Collectively, these studies indicate that many regions in the brain of newborn mice are susceptible to reovirus and that patterns of reovirus infection are not dependent on reovirus receptors SA and PirB.IMPORTANCENeurotropic viruses invade the central nervous system (CNS) and target various cell types to cause disease manifestations, such as meningitis, myelitis, or encephalitis. Infections of the CNS are often difficult to treat and can lead to lasting sequelae or death. Mammalian orthoreovirus (reovirus) causes age-dependent lethal encephalitis in many young mammals. Reovirus infects neurons in several different regions of the brain. However, the complete pattern of CNS infection is not understood. We found that reovirus targets almost all regions of the brain and that patterns of tropism are not dependent on receptors sialic acid and paired immunoglobulin-like receptor B. These studies confirm that two known reovirus receptors do not completely explain the cell types infected in brain tissue and establish strategies that can be used to understand complete patterns of viral tropism in an intact brain.

Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: A retrospective study

To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). A retrospective study was undertaken of patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary outcome was the clinical efficacy of treatment. The secondary outcomes were the bacterial clearance rate and the safety of therapy. In total, 35 patients who received ITH [n=13 (37.1%)] or IVT [n=22 (62.9%)] polymyxin B as combination therapy were included in this study. The median duration of ITH/IVT polymyxin B therapy was 9 (interquartile range 7-11) days. The overall clinical cure rate and bacterial clearance rate were 77.1% and 85.7%, respectively. No adverse effects considered to be related to ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with an Acute Physiology and Chronic Health Evaluation II score ≥15 [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.05-1.42; P=0.038] and a Glasgow Coma Scale score ≤8 (OR 0.69, 95% CI 0.49-0.88; P=0.029). Early administration (≤4 days of infection onset) of ITH/IVT polymyxin B therapy resulted in a significantly higher clinical cure rate (OR 0.65, 95% CI 0.49-1.12; P<0.001), and may reduce the length of treatment and adverse effects. ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can result in greater clinical success.

Filum terminale infected epidermoid cysts in pediatric age group; A case series

BackgroundEpidermoid cysts are rare and account for only 1 % of primary spinal tumors. It's due to inclusion of ectodermal tissue during the third and fourth weeks of gestation. Infected epidermoid cysts are exceedingly rare with very few reports in literature. The clinical presentations include radicular symptoms, motor weakness, sphincteric disturbance, and repeated chemical meningitis. Surgery of this kind of tumor remained a challenge and of a considerable recurrence rate. MethodsThis is a retrospective study reviewing the records of six children who were treated for filum terminale infected epidermoid cysts. All patients underwent microsurgery, and the surgical outcomes were studied through a follow up period of at least 24 months. ResultsAll children had a low back dermal sinus with purulent discharge. One child was a recurrent presentation after the previous two surgeries for evacuation of pus collection, and the other five children were operated for the first time. All the six children had an associated neurological deficit; one child presented with active central nervous system infection, and one child had a history of meningitis and admission to hospital prior to our surgery. Regular follow up revealed no recurrence in any of the six patients. The five patients, who presented with motor weakness, showed significant improvement of the motor power with regular post-operative physical therapy. ConclusionEpidermoid cysts are rare benign lesions that may lead to significant morbidity when infected. The aim of microsurgical excision is to remove the cyst content and its capsule without inducing or increasing neurological deficit by the aid of intraoperative neuromonitoring and microsurgery techniques.

Cerebrospinal Fluid Lactate Levels as a Prognostic Indicator in Patients With Cryptococcal Meningitis Who Are HIV Negative: A Retrospective Cohort Study.

Cryptococcal meningitis (CM) is a severe central nervous system infection. In patients with HIV infections and coexisting CM, elevated baseline cerebrospinal fluid (CSF) lactate levels can predict increased mortality. However, the CSF lactate level's significance in patients with CM who are HIV negative remains unclear, necessitating further investigation to elucidate the potential distinctions and enhance patient management. This study investigated the significance of CSF lactate levels in patients with CM who were HIV negative. This retrospective study utilized data from the clinical databases of patients who underwent lumbar punctures at a medical center in Kaohsiung City, southern Taiwan. Demographic data, CSF lactate levels, routine CSF analyses, and hematologic and neurologic findings were evaluated. The optimal CSF lactate threshold value was determined by the Youden index. This retrospective study included 70 patients with CM, among whom 44 (63%) and 26 (37%) tested negative and positive for HIV, respectively. The group without HIV exhibited higher CSF lactate levels, with an optimal CSF lactate cutoff point of 7.935 mmol/L for predicting 90-day mortality, resulting in significant predictive accuracies (area under the curve, 0.755; sensitivity, 57.1%; specificity, 100%); this value was an independent mortality predictor in patients who were HIV negative. In patients with CM who were HIV negative, CSF lactate levels ≥7.935 mmol/L correlated with higher mortality rates but without statistical significance. All patients with CM who were HIV negative and had CSF lactate levels ≥7.935 mmol/L died within 3 months of admission. Patients with CM who were HIV negative had elevated CSF lactate levels that correlated with adverse outcomes, enabling early identification of high-risk individuals.

Causes of Pediatric Deaths in Lusaka, Zambia: A Quantitative Geographic Information Systems Approach.

While childhood mortality has been declining in Zambia, it remains high at 58 per 1000 live births. Importantly, many leading causes of mortality in Zambia are preventable. This study was conducted to identify clusters of childhood mortality, causes of death of recently deceased children, barriers to care, and risk factors for mortality in Lusaka, Zambia. This study was conducted as a prospective cohort study. Family members or lawfully authorized representatives (LARs) were interviewed when they came to pick up death certificates for recently deceased children from Lusaka Children's Hospital. Each interview included a verbal autopsy, determination of the child's location of residence, and collection of demographic information. Demographic data was also collected from a healthy control group. Quantitative Geographic Information Systems was used to visualize mortality and evaluate for clustering. Leading primary causes of death included malnutrition (21%), complications of chronic illnesses (16%), and central nervous system infections (13%), while the leading barriers to care were cost (58%) and difficulties with travel (53%). Compared to controls, recently deceased children came from families with significantly lower incomes (1905 Kwacha vs. 2412 Kwacha, p = 0.03) and were significantly more likely to have a history of malnutrition (16.7% vs. 1.4%, p = 0.005). Mortality was clustered in two high-population density, low-income neighborhoods in Lusaka. Systems to reduce financial barriers to care and improve access to transportation could reduce childhood mortality in Lusaka. The aforementioned neighborhoods are ideal locations for public health interventions or improved healthcare services.

Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques.

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV and the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and establish a viral reservoir. Given the gaps in our understanding of how these cells respond in vivo to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12 days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the homeostatic and preactivated microglia population decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.

Current Patient Management for Bacterial Meningitis Simultaneously Affected by Stroke.

Bacterial meningitis (BM) is a critical central nervous system infection characterized by increased risks of complications and potentially fatal outcomes. The chances of full recovery are significantly reduced in the presence of concomitant neurovascular complications such as ischemic and hemorrhagic strokes, intracerebral hemorrhage, and cerebral sinus thrombosis. Effective treatment of BM requires a targeted approach that simultaneously addresses the causative pathogen and manages the neurologically related complications. However, clinicians continue to face challenges in determining optimal pharmacotherapy for these patients.The presence of neurological complications is pivotal in determining patient outcomes, contributing to high disability and mortality rates. Early medical management is crucial and begins with essential stabilization followed by rapid diagnostic testing and the administration of empirical broad-spectrum antimicrobial therapy. The use of targeted antibiotics based on culture results is standard, with adjunct therapies such as dexamethasone and, in some cases, anticoagulants playing supportive roles. Despite the deployment of such comprehensive therapeutic strategies, the variability in treatment response and the high incidence of adverse outcomes necessitate ongoing research. This includes exploring novel therapeutic approaches and enhancing current clinical practices through retrospective studies and clinical trials to mitigate the high morbidity and mortality rates associated with BM and its complications. Strategic management is crucial for patient recovery, considering the substantial risk, a broad spectrum of complications, and fatal outcomes from this meningeal infection and stroke. The use of antimicrobial therapy with intravenous adjunct dexamethasone isthe current standard of care for patients with cerebrovascular complications and acute BM. In addition, other options that can provide benefits in complicated cases include anticoagulants and neurosurgery. Further investigation into treatment algorithms for patients with meningeal infection complicated by stroke and/or increased intracranial pressure is still needed.

Optimization of the Diagnosis of Central Nervous System Infections in Vietnamese Hospitals: Results From a Retrospective Multicenter Study.

Central nervous system infections pose significant health challenges, particularly in low- and middle-income countries, because of high morbidity and mortality rates. Rapid and accurate diagnosis is essential for effective treatment to prevent adverse outcomes. Traditional culture-based diagnostics are often slow and lack specificity. This study evaluates the BioFire FilmArray Meningitis/Encephalitis (FAME) Panel against standard diagnostics in Vietnam to assess its clinical impact and suitability for local epidemiology. We conducted a prospective study involving 330 patients with suspected central nervous system infections at 4 hospitals in northern Vietnam from July 2022 to April 2023. Cerebrospinal fluid samples were analyzed using routine culture methods and FAME. We compared pathogen detection rates and assessed the potential clinical impact of FAME results on patient management. Of the 330 cerebrospinal fluid specimens, 64 (19%) were positive by either conventional diagnostics (n = 48) and/or FAME (n = 33). The agreement between FAME and conventional diagnostics was 87%. Key pathogens Mycobacterium tuberculosis (n = 7), Klebsiella pneumoniae (n = 5), Streptococcus suis (n = 5), Epstein-Barr virus (n = 3), Acinetobacter baumannii (n = 1), and Trichosporon asahii (n = 1) were not detected by FAME. Classical meningitis parameter clinical symptoms, altered glucose, protein, and pleocytosis were good predictors of FAME positivity, indicating their utility in optimizing local diagnostic algorithms. FAME complements traditional diagnostics by offering rapid and broad pathogen detection, crucial for timely and appropriate therapy. However, its effectiveness varies with local epidemiology, and it should not replace conventional methods entirely. Tailoring diagnostic panels to regional pathogen prevalence is recommended to enhance diagnostic accuracy and clinical outcomes in low- and middle-income countries.

Melatonin as a Treatment Option for Bacterial Meningitis – A Comprehensive Review

Bacterial meningitis (BM) is a global acute infectious central nervous system (CNS) illness that leaves 50% of survivors with long-term significant consequences. Acute bacterial meningitis is more common in low-resource areas than in high-resource areas. Bacterial survival and multiplication in the circulation, increased permeability of the blood brain barrier (BBB), oxidative stress, and an overactive inflammatory response in the CNS are all involved in the pathogenesis of BM. Because drug-resistant bacteria make treatment for meningitis more difficult, the vaccination has been confined to a few serotypes, and the BM morbidity rate remains high. With recent advances in neurology, there is hope for medication supplements that can successfully prevent and cure BM. Several in vivo and in vitro researches have been conducted to better understand how melatonin affects BM. Melatonin is primarily produced in the pineal gland and has the ability to cross the BBB. Melatonin and its metabolite have been found to be efficient antioxidants and anti-inflammatories, suggesting that they might be used to prevent and treat BM. Melatonin can protect the brain against bacterial meningitis through a variety of mechanisms, including immunological response, antibacterial capabilities, BBB integrity protection, free radical scavenging, anti-inflammation, signalling pathways, and gut microbiota. This paper highlights melatonin's primary neuroprotective processes and investigates prospective preventative and therapy strategies for BM nerve damage. Keywords: Bacterial Meningitis, Neuron Injury, Melatonin, Neuroprotection

Sensory Dysfunction, Microbial Infections, and Host Responses in Alzheimer's Disease.

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways to enter the brain (the "gateway" hypothesis) and the potential feedback loop by which sensory function may be impacted by central nervous system infection. We emphasize detection of sensory changes as first-line surveillance in senior adults to identify and remove potential insults, like microbial infections, that could precipitate brain pathology.

Central Nervous System Infections in Patients With Ventriculoperitoneal Shunts Admitted for Primary Abdominal Infections: A US Nationwide Cohort Analysis.

Although ventriculoperitoneal (VP) shunts are a common treatment for hydrocephalus, there are complication risks including infections. Late complications such as ventriculitis from ascending abdominal infections can have severe consequences. However, the incidence of central nervous system (CNS) infections in VP shunt patients with abdominal infections is not well understood. We aimed to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. Using the National Inpatient Sample, we studied patients from 2016 to 2019 to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. Results were compared with VP shunt patients admitted for primary pneumonia. Among 725 VP shunt patients presenting with abdominal infections, 20 (2.8%) had CNS infections. Chronic obstructive pulmonary disease, hypertension, older age, and a smoking history were more common in patients with CNS infections and primary abdominal infection (P < .05). Patients who developed CNS infection had a significantly higher likelihood of both blood transfusion and coma but a lower likelihood of seizures. VP shunt patients with CNS infections were more likely to undergo shunt removal (odds ratio [OR] = 23.167, P < .001). 4.1% of VP shunt patients with primary abdominal infections died during admission. In a population of primary abdominal infection and pneumonia patients with VP shunts, a multivariate logistic regression analysis controlling for age, sex, and comorbidities identified abdominal infection as an independent risk factor for both CNS infection (OR = 51.208, P < .001) and inpatient death (OR = 3.417, P < .001). Among 6620 VP shunt patients admitted with primary pneumonia, only 5 (0.1%) had CNS infection compared with 20 (2.8%) in those with a primary abdominal infection (OR = 37.532, P < .001), and mortality was 1.6% vs 4.1% for those with a primary abdominal infection (P < .05). CNS infections in VP-shunted patients with abdominal infections are relatively rare but may lead to increased risks of death and other serious adverse outcomes.

Acute necrotizing encephalopathy in adult patients with influenza: a case report and review of the literature

The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22–71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted.

The relationship between mental health problems and risk of infectious diseases: A Mendelian randomization analysis.

The causal effects of mental health problems on the risk of infectious diseases remain vague. Investigating them via observational study is challenging as it presents possible confounding factors. Therefore, the objective of this study was to utilize Mendelian randomization (MR) techniques to evaluate the causal relationship between mental health problems and the risk of infectious diseases. Multivariable MR analyses were performed using genome-wide association data for sleep disorders (N = 216,700), depression (N = 500,199), anxiety (N = 290,361), nervous feelings (N = 450,700), unspecified mental disorder (N = 218,792), pneumonia (N = 486,484), skin and subcutaneous tissue infection (SSTI; N = 218,792), intestinal infectious diseases (IIDs; N = 218,792), urinary tract infection (N = 463,010), and central nervous system (CNS) infections (N = 218,792) among individuals of European ancestry. Independent genetic variants significantly (P < 10-8) associated with each exposure were considered instruments. The primary analysis used an inverse variance-weighted method, followed by a series of sensitivity analyses. Genetically predicted sleep disorders were associated with an increased risk of SSTI (odds ratio [OR], 1.29 [95% confidence interval (CI), 1.05-1.59]; P = .017). Genetically predicted depression was linked with an increased risk of CNS infections (OR, 1.59 [95% CI, 1.00-2.53]; P = .049) and SSTI (1.24 [95% CI, 1.03-1.49]; P = .024). Genetically predicted anxiety was associated with IIDs (OR, 1.19 [95% CI, 1.03-1.37]; P = .017) and SSTI (OR, 1.21 [95% CI, 1.02-1.43]; P = .029). There was no significant causal evidence for genetic prediction of nervous feelings and unspecified mental disorders in IIDs, CNS infections, SSTI, pneumonia, or urinary tract infection. Sensitivity analyses showed that the above causal association estimates were robust. In this MR study, we demonstrated a causal relationship between sleep disorders, depression, anxiety, and the risk of infectious diseases. However, no evidence was found to support causality between nervous feelings, unspecified mental disorders, and the risk of infectious diseases.

The Clinical Manifestations, Risk Factors, Etiologies, and Outcomes of Adult Patients with Infectious Meningitis and Encephalitis: Single Center Experience.

(1) Background: Central nervous system (CNS) infections, including meningitis and encephalitis, are serious conditions which are associated with high morbidity and mortality. This study aims to identify the clinical manifestations, etiologies, and outcomes of meningitis and encephalitis in adult patients in Saudi Arabia, addressing the current gap in understanding these conditions within this population. (2) Methods: This is a single-center retrospective study which included all adult patients diagnosed with meningitis and encephalitis from March 2016 to May 2022. (3) Results: This study found that most cases of meningitis and encephalitis occurred due to unknown pathogens. Pretreatment with antibiotics prior to lumbar puncture (LP) was found in 71.2% of patients with meningitis. Altered mental status and seizures were common presenting symptoms among patients with encephalitis while altered mental status and fever were common among patients with meningitis. (4) Conclusions: Adherence to guidelines in treating meningitis and encephalitis and performing LPs in a timely manner are important. Establishing national biobanks with biological samples from patients suspected of having meningitis or encephalitis will significantly enhance our understanding of these conditions in Saudi Arabia.

Distinct Replication Kinetics, Cytopathogenicity, and Immune Gene Regulation in Human Microglia Cells Infected with Asian and African Lineages of Zika Virus.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes.

Biomarkers and genotypes in patients with Central nervous system infection caused by enterovirus

Purpose Enteroviruses (EV) comprises many different types and are the most common cause of aseptic meningitis. How the virus affects the brain including potential differences between types are largely unknown. Measuring biomarkers in CSF is a tool to estimate brain damage caused by CNS infections. Methods A retrospective study was performed in samples from 38 patients with acute neurological manifestations and positive CSF-EV RNA (n = 37) or serum-IgM (n = 1). The EV in 17 samples were typed by sequencing. The biomarkers neurofilament light (NFL), glial fibrillary acidic protein (GFAP), S-100B protein, amyloid-β (Aβ) 40 and Aβ42, total-tau (T-tau) and phosphorylated tau (P-tau) were measured and compared with data derived from a control group (n = 19). Results There were no increased levels of GFAP (p ≤ 0.1) nor NFL (p ≤ 0.1) in the CSF of patients with EV meningitis (n = 38) compared with controls. However, we found decreased levels of Aβ42 (p < 0.001), Aβ40 (p < 0.001), T-tau (p ≥ 0.01), P-tau (p ≤ 0.001) and S-100B (p ≤ 0.001). E30 (n = 9) and CVB5 (n = 6) were the most frequent EV-types identified, but no differences in biomarker levels or other clinical parameters were found between the infecting virus type. Seven patients who were followed for longer than one month reported remaining cognitive impairment, although no correlations with biomarker concentrations were observed. Conclusion There are no indication of neuronal or astrocyte damage in patients with EV meningitis. Yet, decreased concentrations of Aβ40, Aβ42, P-tau and T-tau were shown, a finding of unknown importance. Cognitive impairment after acute disease occurs, but with only a limited number of patients analysed, no conclusion can be drawn concerning any association with biomarker levels or EV types.

Machine Learning–Based Prediction of Chronic Shunt-Dependent Hydrocephalus After Spontaneous Subarachnoid Hemorrhage

BackgroundChronic posthemorrhagic hydrocephalus often arises following spontaneous subarachnoid hemorrhage (SAH). Timely identification of patients predisposed to develop chronic shunt-dependent hydrocephalus may significantly enhance clinical outcomes. MethodsWe performed an analysis of 510 SAH-patients treated at our institution between 2013 and 2018. Clinical and radiological variables, including age, sex, Hunt & Hess grade, Fisher-Score, external ventricular drainage placement, central nervous system infection, aneurysm characteristics, and treatment modalities, were evaluated. Supervised machine learning models, trained and compared using Python and scikit-learn, were employed to predict chronic shunt-dependent hydrocephalus. Model performance was rigorously assessed through repeated cross-validation. To facilitate transparency and collaboration, we publicly released the dataset and code on GitHub (https://github.com/RISCSoftware/shuntclf) and developed an interactive web application (https://huggingface.co/spaces/risc42/shuntclf). ResultsAmong the evaluated machine learning models, logistic regression exhibited superior performance, with an AUC-ROC of 0.819 and an AUC-PR of 0.482, along with the highest F1 score of 0.473. Although the balanced accuracy scores of the models were generally proximate, ranging from 0.735 to 0.764, logistic regression consistently outperform others in key metrics such as AUC-ROC and AUC-PR. Conversely, female gender and absence of aneurysm within the anterior communicating artery were associated with reduced shunt requirement likelihood. ConclusionMachine learning models, including logistic regression, demonstrate strong predictive capability for early chronic shunt-dependent hydrocephalus following spontaneous SAH, which may potentially contribute to more timely shunt placement interventions. This predictive capability is supported by our web interface, which simplifies the application of these models, aiding clinicians in efficiently determining the need for shunt placement.

MOF-Modified Microrollers for Bioimaging and Sustained Antibiotic Delivery.

Central nervous system (CNS) infections caused by neurosurgery or intrathecal injection of contaminated cerebrospinal fluid are a common and difficult complication. Drug-delivery microrobots are among the latest solutions proposed for antibacterial applications. However, there is a lack of research into developing microrobots with the ability to sustain antibody delivery while can move efficiently in the CNS. Here, biocompatible antibacterial metal-organic framework (MOF)-modified microrollers (MMRs) to combat CNS infections are proposed. The MMRs are iron-based metal-organic framework (NH2-MIL-101(Fe)) modified for enhanced adsorption and Fe/Al coated for magnetic actuation and biocompatibility. The MMRs have demonstrated a faster and unhindered magnetically actuated motion on the uneven biological tissue surface in an organ-on-a-chip that mimicked the CNS compared to it on smooth surface. CFD results consistently align with the experimental findings. The MMRs can be loaded with rhodamine 6G for bioimaging, allowing them to be imaged through sections of the main human tissues by fluorescence microscopy, or tetracycline hydrochloride for antibiotic delivery, allowing them to inhibit the growth of Staphylococcus aureus biofilms by sustained release of antibiotics for 9 days. This study provides a strategy to integrate high-capacity adsorption material with magnetically actuated locomotion for long-term targeted antibacterial applications in biological environments.

An active & passive dual-targeting platform for the precise treatment, process monitoring and effective protection of central nervous system infection

Precise antibacterial activity and effective inflammatory response reduction are critical for successful treatment of Intracranial infection after craniocerebral surgery, which remains an unmet clinical challenge. Herein, an intracranial drug delivery liposome (AFAA-lipo) that possesses dual active&passive targeting capability, direct antibacterial ability, favorable inflammation regulation, and excellent biocompatibility is developed as an antibiotics-free and hardly bacterial-resistance-induced platform for the management of intracranial infection. The surface-anchored specific peptide sequence HRERMS (the oligopeptide designed sourced from β-amyloid precursor protein) makes AFAA-lipo actively penetrate the blood–brain barrier and then perforated and lysed under the stimulation of α-toxin secreted by methicillin-resistant Staphylococcus aureus (MRSA, a severe and widespread intracranial infection type) in the infected site. Our results demonstrate that the AFAA-lipo can eliminate bacteria and biofilms, and reduce inflammatory response through mitochondrial function protection, DNA preservation from damage, TNFR1/NF-κB signaling pathway inhibition, and promotion of microglial polarization towards the anti-inflammatory subtype, ultimately improving post-infection prognosis and survival rate. More interestingly, the pre-intake of AFAA-lipo is capable to reduce MRSA infection risk and alleviate inflammatory response. Furthermore, the near-infrared (NIR) II region imaging fluorescence signal intensity variations of AFAA-lipo is proved the validation to monitor the course of the disease.