Central Nervous System Infection Research Articles

Intraventricular antibiotics for severe central nervous system infections: a case series.

Severe central nervous system infections (CNSI), including community-acquired CNSI (CA-CNSI) and healthcare-associated ventriculitis and meningitis (HAVM), present high morbidity and mortality. Intraventricular antibiotic treatment (IVT) is advisable for these infections, though evidence is limited. We retrospectively analyzed data on 27 patients who received IVT for severe CA-CNSI and HAVM over 10 years, assessing clinical and paraclinical features, such as baseline severity and functional outcome, antibiotics, microbiological and laboratory data. Comparisons were made between patients affected by CNSI and HAVM and those with favorable and unfavorable outcomes, based on the modified Rankin scale.Gram-positive organisms dominated in CA-CNSI (64%), while gram-negative organisms were more frequent in HAVM (64%). Patients received a median of 30 days of intravenous antibiotics and 11 days of IVT, with no significant difference between CA-CNSI and HAVM. IVT-associated toxicity was rare. Patients with favorable outcomes (64%) had higher initial cerebrospinal fluid- white blood cell count (CSF-WBC), that decreased more rapidly than in patients with unfavorable outcomes. CSF-WBC dynamics did not differ between CA-CNSI and HAVM patients.Rapid decline in CSF-WBC after initiation of IVT was associated with favorable outcome. Despite severe neurological impairment at admission, most survivors achieved favorable long-term outcomes.

Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases

Metagenomic next-generation sequencing (mNGS) is a transformative approach in the diagnosis of infectious diseases, utilizing unbiased high-throughput sequencing to directly detect and characterize microbial genomes from clinical samples. This review comprehensively outlines the fundamental principles, sequencing workflow, and platforms utilized in mNGS technology. The methodological backbone involves shotgun sequencing of total nucleic acids extracted from diverse sample types, enabling simultaneous detection of bacteria, viruses, fungi, and parasites without prior knowledge of the infectious agent. Key advantages of mNGS include its capability to identify rare, novel, or unculturable pathogens, providing a more comprehensive view of microbial communities compared to traditional culture-based methods. Despite these strengths, challenges such as data analysis complexity, high cost, and the need for optimized sample preparation protocols remain significant hurdles. The application of mNGS across various systemic infections highlights its clinical utility. Case studies discussed in this review illustrate its efficacy in diagnosing respiratory tract infections, bloodstream infections, central nervous system infections, gastrointestinal infections, and others. By rapidly identifying pathogens and their genomic characteristics, mNGS facilitates timely and targeted therapeutic interventions, thereby improving patient outcomes and infection control measures. Looking ahead, the future of mNGS in infectious disease diagnostics appears promising. Advances in bioinformatics tools and sequencing technologies are anticipated to streamline data analysis, enhance sensitivity and specificity, and reduce turnaround times. Integration with clinical decision support systems promises to further optimize mNGS utilization in routine clinical practice. In conclusion, mNGS represents a paradigm shift in the field of infectious disease diagnostics, offering unparalleled insights into microbial diversity and pathogenesis. While challenges persist, ongoing technological advancements hold immense potential to consolidate mNGS as a pivotal tool in the armamentarium of modern medicine, empowering clinicians with precise, rapid, and comprehensive pathogen detection capabilities.

Treatment outcome in patients with spinal neurocysticercosis: a systematic review of published cases and case series.

Spinal neurocysticercosis is a rare central nervous system infection caused by the larval form of the Taenia solium. Due to its rarity, most knowledge is derived from isolated case reports. This review aims to evaluate existing case reports and observational studies to provide a comprehensive overview of the disease's clinical presentation and treatment outcomes. Following PRISMA guidelines, a comprehensive search was performed across various databases. The review included case reports, case series, and observational studies, and it is registered with PROSPERO (CRD42024496957). This review analyzed 206 spinal neurocysticercosis cases (from 171 published reports). Symptoms persisted for one week to six months in 49% of cases, and common presentations included paraparesis/quadriparesis (61.7%) and neck/limb/back pain (40.8%). CSF abnormalities were observed in 23.8%. Thoracic involvement was most frequent (39.3%), followed by cervical (27.2%). Neurocysticercosis lesions in other regions, primarily the brain, were found in 18.9%. Differential diagnoses included spinal cord tumors (13.1%). Treatment often involved surgery alone (32%) or with cysticidal drugs (45.6%), with a 91.3% improvement rate, indicating favorable outcomes. Spinal neurocysticercosis primarily affects the thoracic and cervical regions. Most patients respond well to medical therapy; surgery is mainly for progressive neurological deficits.

Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections.

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection.

An Investigation into Diagnostic Strategies for Central Nervous System Infections Through the Integration of Metagenomic Next-Generation Sequencing and Conventional Diagnostic Methods.

The optimal strategy for detecting central nervous system infections (CNSI) in cerebrospinal fluid (CSF) samples remains unclear. In a one-year, multicenter retrospective study, we examined the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional pathogen diagnostic techniques for CSF in diagnosing CNSI. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index for each diagnostic approach. Additionally, receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was determined to assess the diagnostic performance of each method. The study included 68 patients, comprising both adults and children, who were suspected of having CNSI. Through the application of comprehensive clinical interpretation (CCI), the sensitivity and specificity of mNGS were found to be 67.6% (95% confidence interval [CI]: 50.85-80.87%) and 45.8% (95% CI: 27.89-64.92%), respectively. In comparison, traditional pathogenic diagnostic methods indicated that the culture method demonstrated a sensitivity of 10.6% (95% CI: 4.63-22.6%) and a specificity of 100% (95% CI: 84.54-100%). Furthermore, the sensitivity and specificity of the peripheral blood nucleated cell count were determined to be 34.0% (95% confidence interval: 22.17-48.33%) and 57.1% (95% confidence interval: 36.54-75.53%), respectively. CSF nucleated cell count demonstrated a sensitivity of 66.0% (95% confidence interval [CI]: 51.67-77.83%) and a specificity of 61.9% (95% CI: 40.87-79.25%). In comparison, the CSF protein content exhibited a sensitivity of 63.8% (95% CI: 49.54-76.03%) and a specificity of 57.1% (95% CI: 36.54-75.53%). When combining mNGS with traditional methodologies, the overall sensitivity increased to 91.3% (95% CI: 79.67-96.56%), although the specificity was reduced to 18.2% (95% CI: 7.31-38.51%). The area under the ROC curve for culture, peripheral blood nucleated cell count, mNGS, CSF nucleated cell count, and CSF protein content were 0.8088, 0.6038, 0.6103, 0.5588, and 0.5588, respectively. The variation in CSF nucleated cell count did not significantly affect the diagnostic efficacy of mNGS. Currently, both mNGS and traditional diagnostic methods encounter substantial challenges in diagnosing CNSI.

Epidemiological Characteristics of Neuro-Specific Antibodies Following Viral Infections.

This study aims to explore the epidemiological characteristics of neuro-specific antibodies (ns-Ab) induced by different viral infections within the central nervous system (CNS). Additionally, it seeks to compare the autoimmune effects following several typical viral infections in CNS. We conduct a retrospective study to compare and analyze the prevalence trends of ns-Ab in patients with different viral infections. Additionally, evaluate the intensity of CNS inflammatory responses postviral infection by correlating clinical characteristics and laboratory findings, and briefly demonstrate the immune effects in CNS following various viral infections. This study retrospectively collected data from 1037 patients hospitalized with suspected CNS infections. A total of 654 patients (63.1%) were included in the final analysis. A higher proportion of patients with pathogens present in their cerebrospinal fluid (CSF) (114 out of 332, 34.3%) tested positive for ns-Ab compared to those without pathogens (70 out of 322, 21.7%) (p = 0.0004). Specifically, the screening rate for ns-Ab in patients with CNS viral infections (83 out of 165, 50.3%) and the prevalence of ns-Ab (27 out of 83, 32.5%) were significantly higher than in those with other pathogen infections (p < 0.0001 and p = 0.016, respectively). Among these, human herpesvirus 7 (HHV7) patients had the highest detection rate of ns-Ab during the disease course (11 out of 26, 42.3%), but exhibited infection characteristics distinctly different from those of herpes simplex virus 1 (HSV1). Viral infections significantly promote the development of autoimmune responses in CNS. The production of ns-Ab and the subsequent autoimmune response vary across different viral infections. There is a strong statistical correlation between HHV7 and the presence of ns-Ab, suggesting that HHV7 may serve as an early indicator of secondary autoimmune response following CNS infections.

Molecular Analysis of Coxsackievirus B2 Associated With Severe Symptoms of the Central Nervous System.

Coxsackievirus B2 (CVB2) is a member of the enterovirus group known to induce a spectrum of illnesses, from mild to severe. In the summer of 2022, an unusual outbreak of enteroviral central nervous system (CNS) infections occurred that was attributed to CVB2. Cerebrospinal fluid (CSF) samples collected from patients in 2015-2022 were tested for enterovirus via RT-PCR, followed by Sanger sequencing for positive cases. CVB2 samples were further sequenced in the P1 region using NGS. A total of 30 CSF samples were identified as CVB2, with 60% of these cases occurring between June and August 2022. The 2022 CVB2 variants were associated with severe clinical symptoms, including encephalitis (50%) and ataxia (27.8%). Samples from 2015 to 2020 were also included due to the absence of these symptoms. Phylogenetic analysis revealed that CVB2 strains from 2019 to 2020 were also distinct from those obtained in 2022. Amino acid analysis of the capsid proteins VP1, VP2, and VP3 identified three unique substitutions with potential antigenic significance in the 2022 variant: S67A in VP2, and T93A and E274D in VP1. These substitutions were not present in earlier strains or reported in the literature, suggesting they may influence the virus's virulence. The clinical observations from this study highlight new patterns of CVB2 infection in the CNS that had not been previously observed. Additionally, it identifies unique genetic changes in the 2022 CVB2 variant that may account for the increased virulence seen in the 2022 outbreak. However, further analysis is required to validate this assumption.

Epstein-Barr Virus Encephalitis Involving the Bilateral Corticospinal Tract: Wine Glass Sign

Epstein-Barr virus (EBV) causes a variety of central nervous system infections, including encephalitis. EBV encephalitis accounts for approximately 5.8% of all viral encephalitis, with fever, headache, convulsions, and decreased consciousness as common symptoms. Brain magnetic resonance imaging (MRI) in EBV encephalitis shows high signal intensity mainly in the parieto-occipital cortex, subcortical white matter, and deep gray matter nuclei with reversibility. In this report, we present a case of bilateral corticospinal tract involvement (wineglass sign) identified on brain MRI in a patient with diagnosed with EBV encephalitis.

Epstein–Barr Virus encephalitis associated hemophagocytic lymphohistiocytosis in childhood-onset systemic lupus erythematosus: a case-based review

BackgroundHemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation that results in an uncontrolled hyperinflammatory state. HLH is classified into two main categories: primary (familial) HLH and secondary (acquired) HLH. Secondary HLH can result from various underlying, including infection-associated hemophagocytic syndrome (IAHS) and macrophage activation syndrome (MAS) associated with rheumatologic disorders, among others. Epstein–Barr virus (EBV) often causes IAHS, but central nervous system (CNS) involvement is rare among systemic lupus erythematosus (SLE) patients. We report a case of EBV encephalitis associated with HLH in a patient with childhood-onset SLE.Case presentationA 12-year-old girl had received a diagnosis of SLE 2 months before presentation. After a period of inactive disease on treatment, fever and seizures, with altered mental status and hallucinations, developed over several weeks. A complete blood cell count (CBC) revealed pancytopenia, accompanied by elevated levels of inflammatory markers: 86 mm/hr erythrocyte sedimentation rate, 8.9 mg/dl c-reactive protein, and 3,966 ng/mL of ferritin. The differential diagnosis included active neuropsychiatric SLE, CNS infection and neurological manifestations in secondary HLH, which could have represented either IAHS or MAS. Meropenem and acyclovir were initially administered for clinical acute encephalitis, followed by pulse methylprednisolone; however, the fever persisted, and another CBC revealed progressive cytopenia. A bone marrow study showed hypocellularity and active hemophagocytic activity, and intravenous immunoglobulin was additionally given due to the diagnosis of HLH. Cerebrospinal fluid (CSF) analysis showed 60/mm3 white blood cells (N 55%, L 45%), 141 mg/dL glucose (0.7 blood-CSF glucose ratio), < 4 mg/dL protein; results of Gram stain and bacterial culture were negative. The viral encephalitis panel from the CSF confirmed EBV infection. Bone marrow immunohistochemistry examination revealed increasing levels of CD8 + T-cell and equivocal positive results for EBV-encoded RNA in situ hybridization; therefore, HLH potentially associated with EBV was diagnosed. After treatment with IVIg, cyclosporin A, and prednisolone, the patient’s symptoms gradually improved and she was eventually able to return to school.ConclusionsOur case highlights the importance of a thorough differential diagnosis, including EBV encephalitis associated with HLH, in patients with childhood SLE, particularly in cases of clinical deterioration occurs after initial treatment.

Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity.

Herpes simplex virus type 1 (HSV-1) primarily targets the oral and nasal epithelia before establishing latency in the trigeminal ganglion (TG) and other peripheral ganglia. HSV-1 can also infect and become latent in the central nervous system (CNS) independent of latency in the TGs. Recent studies suggest entry to the CNS via two distinct routes: the TG-brainstem connection and olfactory nerve; however, to date, there is no characterization of brain regions targeted during HSV-1 primary infection. Furthermore, the immune response by microglia may also contribute to the heterogeneity between different brain regions. However, the response to HSV-1 by microglia has not been characterized in a region-specific manner. This study investigated the time course of HSV-1 spread within the olfactory epithelium (OE) and CNS following intranasal inoculation and the corresponding macrophage/microglial response in a C57BL/6 mouse model. We found an apical to basal spread of HSV-1 within the OE and underlying tissue accompanied by an inflammatory response of macrophages. OE infection was followed by infection of a small subset of brain regions targeted by the TG in the brainstem and other cranial nerve nuclei, including the vagus and hypoglossal nerve. Furthermore, other brain regions were positive for HSV-1 antigens, such as the locus coeruleus (LC), raphe nucleus (RaN), and hypothalamus while sparing the hippocampus and cortex. Within each brain region, microglia activation also varied widely. These findings provide critical insights into the region-specific dissemination of HSV-1 within the CNS, elucidating potential mechanisms linking viral infection to neurological and neurodegenerative diseases.IMPORTANCEThis study shows how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveal the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigens. Previous reports have identified specific brain regions found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the brain regions consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases.

Eosinophilic Meningitis in a Patient With Early HIV Infection, Latent Syphilis and HSV-2 Meningitis

Abstract Eosinophilic meningitis is an unusual condition, particularly in patients with HIV infection or syphilis. The detection of herpes simplex virus (HSV)-2 and HIV-1 in cerebrospinal fluid from a patient with acute eosinophilic meningitis has not been previously reported. Herein, we report a case of a 26-year-old cisgender man newly diagnosed with HIV-1 infection and latent syphilis, presenting with headache and low-grade fever. He was diagnosed with both acute eosinophilic meningitis and HSV-2 meningitis, and his condition improved after treatment with acyclovir and penicillin. The compelling case indicates that HSV-2 meningitis may manifest concurrently with acute eosinophilia meningitis in patients coinfected with HIV and Treponema pallidum. Metagenomics next-generation sequencing plays an important role in identifying and further confirming pathogens responsible for central nervous system infections.

Elements of dissemination in cryptococcosis.

As healthcare improves and our ability to support patients with compromised immune systems increases, such patients become more vulnerable to microbes in the environment. These include fungal pathogens such as Cryptococcus neoformans, the primary cause of fungal meningitis and a top priority pathogen on the World Health Organization fungal pathogen list. Like many other environmental pathogens, C. neoformans must adapt to and thrive in diverse environments in order to cause disease: (i) the environmental niche, (ii) the lungs following inhalation of infectious particles, (iii) the bloodstream and/or lymphatic system during dissemination, and (iv) the central nervous system (CNS), where it causes a deadly cryptococcal meningoencephalitis. Because CNS infection is the driver of mortality and the presenting illness, understanding the dissemination process from both host and fungal perspectives is important for treating these infections. In this review, we discuss the different stages of dissemination, how fungal cells interact with host cells during disease, and the ability to adapt to different environments within hosts.

Emergence of a New Pathogen: A Retrospective Study of HPeV-5 Central Nervous System Disease in Alberta, Canada

Human parechoviruses (HPeVs) are known to cause meningo-encephalitis among neonates and infants. We aimed to describe the epidemiology of HPeVs causing central nervous system infections in Alberta from 2014 to 2019 with comparison of known HPeV-3 and emerging HPeV-5. Genomic analysis was completed on a subset of HPeV-5 strains to understand genetic relatedness to other known strains. All cerebrospinal fluid (CSF) samples in Alberta with detection of HPeVs were identified and a case review of medical records was conducted, retrospectively, to gather demographic and clinical details. Descriptive and analytic statistics were used to describe and compare the characteristics of cases affected by HPeV-3 with HPeV-5. Genome amplification was completed on six HPeV-5 samples. During the study period, 18,882 CSF samples were tested; 56 were positive for HPeV-3 or HPeV-5, and 52 patients were included in this study (40 HPeV-3 cases and 12 HPeV-5). A total of 40% of cases occurred in 2016, and 64% of infections occurred in the months of August to October. The mean age of cases was 18 days for HPeV-5 compared with 26 days for HPeV-3 (p = 0.045). Phylogenetic comparison showed similarity to a recombinant strain reported in Australia. HPeV meningo-encephalitis affected neonates/infants, mostly in late summer/early fall, and genomic sequencing of new strains can contribute to understanding the epidemiology of HPeV infections globally.

The Biological Changes of Synaptic Plasticity in the Pathological Process of Sepsis-associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a form of cognitive and psychological impairment resulting from sepsis, which occurs without any central nervous system infection or structural brain injury. Patients may experience long-term cognitive deficits and psychiatric disorders even after discharge. However, the underlying mechanism remains unclear. As cognitive function and mental disease are closely related to synaptic plasticity, it is presumed that alterations in synaptic plasticity play an essential role in the pathological process of SAE. Here, we present a systematic description of the pathogenesis of SAE, which is primarily driven by glial cell activation and subsequent release of inflammatory mediators. Additionally, we elucidate the alterations in synaptic plasticity that occur during SAE and comprehensively discuss the roles played by glial cells and inflammatory factors in this process. In this review, we mainly discuss the synaptic plasticity of SAE, and the main aim is to show the consequences of SAE on inflammatory factors and how they affect synaptic plasticity. This review may enhance our understanding of the mechanism underlying cognitive dysfunction and provide valuable insights into identifying appropriate therapeutic targets for SAE.

Carbon monoxide poisoning is associated with an increased risk of epilepsy and status epilepticus: a nationwide population-based cohort study conducted in the Republic of Korea between 2002–2021

Introduction Carbon monoxide poisoning may result in various neurological injuries, including acute symptomatic seizures. We aimed to investigate the long-term risk of epilepsy and status epilepticus in patients with previous carbon monoxide poisoning. Methods The study population was derived from the National Health Insurance Service database of the Republic of Korea between 1 January 2002 and 31 December 2021. We included adults with at least one documented visit to medical facilities because of carbon monoxide poisoning (International Classification of Diseases, Tenth Revision, code T58). Patients were matched, on the same index date, with controls, without a T58 code, for age, sex, insurance type, income level, and residence location in a 1:1 ratio. Follow-up continued until death, migration, or the end of the observation period (31 December 2021). The primary outcome was the incidence of epilepsy (codes G40 or R56) and status epilepticus (code G41). Results This study included 53,380 patients with carbon monoxide poisoning and 53,380 controls, with 44.2% women and a mean age of 45.7 years. The mean (±SD) follow-up period was 5.7 ± 4.3 years in the carbon monoxide poisoned group and 6.4 ± 4.4 years in controls. The overall risk of epilepsy (adjusted hazard ratio 2.60; 95% CI: 2.43–2.78; P < 0.001) and status epilepticus (adjusted hazard ratio 4.10; 95% CI: 2.84–5.92; P < 0.001) was significantly increased in the carbon monoxide poisoned group compared to controls. The risk of epilepsy and status epilepticus was increased in patients with previous carbon monoxide poisoning, regardless of sex, age or a history of stroke, neurodegenerative diseases, or central nervous system tumour or infection. However, in the subgroup analysis according to age, the highest risk of epilepsy and status epilepticus was observed in patients less than 40 years of age. Discussion In this population-based cohort study, previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus. The risk was more noticeable in patients aged less than 40 years. Further studies are needed to confirm such an association in other populations. Conclusions Previous carbon monoxide poisoning was associated with an increased risk of epilepsy and status epilepticus, particularly in the younger population. The long-term management of survivors of carbon monoxide poisoning should include monitoring for epilepsy and status epilepticus.

A predictive model for secondary central nervous system infection after craniotomy based on machine learning

To analyze the risk factors of secondary Central nervous system infections (CNSIs) after craniotomy, and to establish an individualized predictive model for CNSIs risk. The independent risk factors were screened by univariate and multivariate logistic regression analysis. Logistic regression, naive bayes, random forest, light GBM and adaboost algorithms were used to establish predictive models for secondary CNSIs after craniotomy. The predictive model based on the Adaboost algorithm demonstrated superior prediction performance compared to the other four models. Under 5-fold cross validation, the accuracy was 0.80, the precision was 0.69, the recall was 0.85, the F1-score was 0.76, the area under the ROC curve was 0.897,and the average precision was 0.880. The top 5 variables of importance in Adaboost model were operation time, indwelling time of lumbar drainage tube, indwelling lumbar drainage tube during operation, indwelling epidural drainage tube during operation, and GCS score. In addition, Adaboost model with the best prediction performance was used for clinical verification, and the prediction results were compared with the actual occurrence of CNSIs after surgery. The results showed that the accuracy of Adaboost model in predicting CNSIs was 60%, the accuracy of Adaboost model in predicting non-CNSIS was 92%, and the overall prediction accuracy was 76%.

Severe infections as risk factors for acute myocardial infarction: a nationwide, Danish cohort study from 1987 to 2018

Abstract Aims Infections have been associated with acute myocardial infarction (AMI), but differences in risk between infection types and age groups are unclear. This study aims to investigate whether infections are associated with subsequent AMI and whether the risk differs across infection sites and age groups. Methods and results Nationwide registers were used to include 702 596 adults hospitalized between 1987 and 2018 with either pneumonia (n = 344 319), urinary tract infection (UTI) (n = 270 101), soft tissue/bone infection (n = 66 718), central nervous system (CNS) infection (n = 17 025), or endocarditis (n = 4433). Patients were sex and age matched with two unexposed controls. Outcome was first-time AMI within 10 years. A time-dependent Cox proportional hazards model with cut-offs at 30 and 90 days was used for calculating adjusted hazard ratios (HRs). Pneumonia, UTI, and soft tissue/bone infection were associated with increased relative rates of AMI compared to matched, unexposed controls. Highest relative rates were found within the first 0–30 days post-exposure: pneumonia: HR 3.39 [95% confidence interval (CI) 3.15–3.65]; UTI: HR 2.44 (95% CI 2.21–2.70); soft tissue/bone infection: HR 1.84 (95% CI 1.45–2.33). Relative rates decreased over time but remained significantly elevated throughout the follow-up period and were increased in all age groups. No association was found for CNS infection and for endocarditis only at 31–90 days, HR 2.28 (95% CI 1.20–4.33). Conclusion Acute infections are associated with increased relative rates of AMI across different infection sites and age groups with higher relative rates found for pneumonia. This indicates that some infections may act as a trigger for AMI with a site and/or pathogen specific risk.

State-of-the-art cranial ultrasound in clinical scenarios for infants born at term and near-term.

Neonates admitted to the intensive care unit are at risk of brain injury. Importantly, infants with signs of neurological impairment need prompt diagnosis to guide intervention. Cranial ultrasound (CUS) is the first-line imaging tool for infants born preterm. New developments in this technology, which now incorporates high-resolution equipment, have notably improved the performance of CUS in infants born at term and near-term. On the other hand, the potential of CUS as a diagnostic tool in older infants is less established. The lack of studies focusing on this topic, local protocol variability among clinical sites, and divergent opinions on CUS patterns of disease entities are the main constraints. This review provides an overview of state-of-the-art CUS as a decision-making tool under different clinical scenarios, such as neonatal encephalopathy, seizures, and suspected central nervous system infection. The CUS features that characterize several patterns supporting a diagnosis are detailed, focusing on haemorrhage and infection.

Comparative study of pathogen detection methods for central nervous system infections: laboratory testing of tuberculous meningitis

BackgroundTuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability.MethodsA cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods.ResultsAmong the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate.ConclusionsThis study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Unusual late presentation of cryptococcal meningitis with simultaneous CMV antigenemia in a kidney transplant recipient.

Cryptococcosis is the third most common invasive fungal infection in solid-organ transplant (SOT) recipients after candidiasis and aspergillosis. These patients are at risk of disseminated cryptococcosis because of immuosuppressive therapy. The median time to disease onset after kidney transplantation is approximately 35months and it rarely occurs more than 10years after transplantation. Herein, we report a case of 64-year-old kidney transplant recipient suffering from coexisting disseminated cryptococcosis with brain and skin involvement, together with cytomegalovirus (CMV) antigenemia more than 20years after transplant. She presented with frontal headache and bilateral hand tremor, in addition to multiple nodular lesions over bilateral lower limbs. The diagnosis was made after lumbar puncture and skin biopsy. She was successfully treated with a course of anti-fungal and anti-CMV regimen without any relapse of central nervous system infection. Our case illustrates that disseminated cryptococcosis can occur very late after organ transplant. It is thus important to watch out for late-onset opportunistic infections and strike the balance between risks of infections and rejections in SOT patients.