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Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a \"platform\" for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.

Background Recently, increased reports reveal that anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs) are strongly associated with several severe disseminated infections. However, reports on AIGAs with central nervous system (CNS) infections are rare. Here, we described three AIGAs-positive adults who had persistent or recurrent disseminated infections caused by Talaromyces marneffei (TM), nontuberculous mycobacteria (NTM), mycobacterium tuberculosis (TB), or other pathogens, accompanied with CNS infections. In addition, we conducted a thorough literature review of AIGAs-positive patients with CNS infections. Case presentation We report three HIV-negative cases of recurrent disseminated infections including CNS, and AIGAs were measured. All patients had no history of underlying diseases or immunosuppression and presented with fever, cough, and headache. They were negative for HIV antibodies but positive for AIGAs. The patients were diagnosed with CNS infections based on cerebrospinal fluid (CSF) examination and next-generation sequencing (NGS). All patients received anti-infective treatment according to different pathogens, and their condition remained stable without recurrence. Conclusions In adults with severe and recurrent infections of multiple organs without known immunodeficiency, adult-onset immunodeficiency (AOID) associated with AIGAs should be considered. In AIGAs-positive patients, the blood–brain barrier (BBB) may be disrupted, leading to susceptibility to CNS infections.

Background Pediatric CNS infections have been identified as a global health problem, associated with an increased death rate and fatal consequences. Pentraxin 3 (PTX3) is an acute-phase mediator that increases in body fluids and plasma throughout inflammation. Our study was designed to assess the diagnostic and prognostic value of cerebrospinal fluid (CSF) PTX3 levels in pediatric patients with different central nervous system (CNS) infections. Methods We enrolled 100 children hospitalized at Fayoum University Children’s Hospital with suspected CNS infections fulfilling the case criteria for CNS infections. We recorded their medical history and examination data upon admission. The C-reactive protein (CRP) level, complete blood count (CBC), CSF PTX3 level, CSF analysis and culture, and blood culture were assessed in all patients at the time of admission. Results Levels of PTX3 were significantly correlated with the duration of symptoms before admission, length of hospital stay, patient outcomes, CRP levels, CSF findings, and CSF cultures  (P value  <  0.001) . Patients who needed mechanical ventilation or experienced adverse outcomes had greater levels of PTX3, which were more prevalent in those with a bacterial etiology (P value  <  0.05). Conclusion PTX3 indicates disease severity and prognosis. PTX3 showed statistically significant sensitivity when discriminating between bacterial and aseptic CNS infections, as well as between bacterial CNS infections and controls. However, it has lower sensitivity and specificity than other CSF biomarkers, though it is higher than serum CRP.

Infections of central nervous system (ICNSs) are inflammatory diseases caused by infectious agents that can infiltrate the brain and spinal cord through various routes, including the bloodstream, peripheral nerves, or cranial nerves. Exosomes are found in plasma and have the capacity to cross the blood–brain barrier (BBB). Exosome constituents, including lipids, proteins, DNA, and RNA, change significantly over time and are correlated with the course of disease. Circular RNA (circRNA) has become a potential biomarker for various diseases, such as ICNSs. This study explores the diagnostic potential of circRNAs derived from brain‐derived exosomes in ICNSs. Our research shows that the brain‐derived exosomes from patients with CNS illnesses have different patterns of circRNA expression than those from healthy controls. Plasma samples from patients with bacterial ICNSs show significantly elevated levels of hsa_circ__0020840 and hsa_circ_0116108. In contrast, higher expression levels of hsa_circ_0056947 and hsa_circ_0021531 are observed in plasma samples from individuals with viral ICNSs compared to healthy subjects. These observations suggest their potential utility as sensitive and specific biomarkers for these diseases. Moreover, the capacity of circRNAs to be encapsulated within exosomes and released into circulation offers a noninvasive approach for diagnosing ICNSs. These findings highlight the promise of utilizing brain‐derived exosomal circRNAs as novel diagnostic markers for ICNSs, which may have implications for improving patient outcomes and disease management.

The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients fromGauteng, South Africa. This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR.Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using EpiInfo. MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria.Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample).Two of the four Middelburg virus positive cases,for which clinical information was available, had other comorbidities or infections at the time of infection. Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.

Reports on central nervous system (CNS) infection caused by varicella-zoster virus (VZV) reactivation are increasing, but its pathogenesis remains unclear, which causes delayed diagnosis and treatment. Some studies suggested that hypercoagulability is involved in the pathogenesis of CNS infection of VZV. This study investigated the coagulation parameters of herpes zoster (HZ) and their correlations with the VZV-related CNS infection, and provided a reference for the early diagnosis and treatment. We selected 123 consecutive patients, including 95 HZ cases and 28 VZV meningitis (VZVM) cases hospitalized due to HZ. Forty-seven patients who underwent physical examination in our hospital were used as Health controls (HCs) group. The coagulation parameters of the three groups were measured and compared, and the correlation between coagulation function parameters and CNS infection was analyzed by Logistic regression. the expression of coagulation factor in cerebrospinal fluid (CSF) proteomics of 28 VZVM patients and 11 HZ patients were analyzed. Compared with HCs group, plasma Fibrinogen (Fib) and D-dimer (DD) levels in HZ and VZVM group were significantly increased (P <0.01), while there were no significant differences in other parameters (P > 0.05). There was also no significant difference in the levels of coagulation parameters between the HZ and VZVM groups (P > 0.05). Proteomic analysis of CSF revealed that there was no difference in the expression levels of Fib, Antithrombin III (AT-III), and coagulation factors VII, IX, X, XI in the HZ and VZVM patients (P > 0.05). The expression levels of coagulation factors XII and XIIIa were higher in VZVM patients than those in HZ patients (P < 0.05 and P < 0.01, respectively). In HZ and VZVM patients, a hypercoagulable state was observed with increased Fib and DD levels. However, hypercoagulation was not a risk factor for CNS infection, and there was no significant correlation between the elevated level and the severity of disease.

Enterovirus 71 (EV71) infection can lead to devastating clinical outcomes. An appreciation of the scientific relationship between cytokine response and patient mortality may help limit the risks posed by this deadly illness. We present the results of a study that compared the cerebrospinal fluid (CSF) and serum levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in 24 patients with EV71 infection. Cases in this study involved diverse manifestations or complications, including encephalitis, poliomyelitis-like syndrome, meningitis, and pulmonary edema. CSF levels of IL-6 in study patients were found to be consistently higher during the first 2 days of central nervous system (CNS) involvement than afterward. Compared with patients who did not have pulmonary edema, patients who experienced pulmonary edema had dramatically varied blood values, including IL-6, white blood cell counts, and glucose levels. Our findings suggest that the combination of CNS and systemic inflammatory response may trigger EV71-related cardiopulmonary collapse.

Background Accurate antemortem EPM diagnosis requires evidence of intrathecal antibody production. Some advocate the use of acute phase proteins in addition to serology, which alone results in substantial false positives. Hypothesis/Objectives The purpose of this study was to determine if serum C‐reactive protein (CRP) or serum amyloid A (SAA) concentrations were elevated in cases of equine protozoal myeloencephalitis (EPM) compared to other neurological diseases. Animals 25 clinical cases of equine neurological disease: EPM (10), cervical vertebral stenotic myelopathy (CVSM) (10), neuroborreliosis (2), equine motor neuron disease (1), degenerative myelopathy (1), and leukoencephalomalacia (1). Methods Serum and CSF CRP and SAA were measured. Selection criteria included neurologic disease, antemortem diagnosis of EPM or CVSM, or postmortem diagnosis of EPM, CVSM, or other neurologic disease, and availability of serological results and archived samples for testing. Results Serum SAA and serum CRP levels were generally undetectable or low in horses with EPM (median CRP ≤0.1 mg/L, ≤0.1‐14.4 mg/L; median SAA ≤0.1 mg/L, ≤0.1‐6.11 mg/L) and CVSM (median CRP ≤0.1, ≤0.1‐2.41 mg/L; median SAA ≤0.1mg/L, ≤0.1‐13.88 mg/L). CSF CRP and SAA for horses with EPM (median CRP 3.35 mg/l, 0.19‐13.43 mg/l; median SAA ≤0.1 mg/L, ≤0.1‐2.4 mg/L) and CVSM (median CRP 4.015 mg/L, 0.16‐9.62 mg/L; median SAA 0.62 mg/L, ≤0.1‐2.91 mg/L) were also undetectable or low. Kruskal–Wallis test showed no statistically significant differences between serum CRP (P = .14), serum SAA (P = .79), spinal fluid CRP (P = .65), or spinal fluid SAA between horses with EPM and CVSM (P = .52). Conclusion Neither SAA nor CRP in serum or CSF aid diagnosis of EPM.

We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC )/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 μg/mL, whereas it could be achieved in CSF with a MIC of ≤1 μg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 μg/mL. For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.