Search Results (120)

Background: Etiologic diagnosis in suspected viral meningitis is not always achievable, yet it can play a significant role in patient management. Our study aimed to do a comprehensive analysis of current practices regarding etiologic diagnosis in these cases and compare patients with and without known etiologic diagnosis in order to visualize if and how having an etiological diagnosis can impact patient management and/or outcome. Methods and results: We conducted a convergent mixed-methods study. Quantitative data was obtained from 118 patients hospitalized during a one-year period. There were 40.7% (n = 48) cases with unknown etiology. The length of hospitalization was longer in the group with unknown etiology vs. known etiology (12.6 days vs. 9.8 days p = 0.01). Thematic analysis was used for the qualitative approach in order to evaluate physicians’ overall perceptions regarding this subject. Conclusions: Our mixed-methods study shows that while clinicians consider etiologic diagnosis very important, it remains a diagnostic challenge even in modern times. Continued efforts are needed to optimize diagnostic strategies and address existing gaps in the etiologic workup of viral meningitis. There may be overlooked pathogens that have cost-efficient testing methods, like TBEV, that can be introduced in a testing protocol and may enhance patient management and reduce unnecessary hospital stays. Full article

Coxsackievirus B3 (CV-B3) infection causes inflammatory conditions such as viral myocarditis and meningitis, and incidence rates are rising annually. While children are more likely to be affected by severe manifestations, the molecular basis of this age-dependent susceptibility is poorly understood. In this study, we used young Balb/c mice at three developmental stages (7-, 14-, and 30-day-old mice) to investigate CV-B3 pathogenesis. Our findings revealed that 7-day-old mice exhibited substantial infection susceptibility and pathological severity compared to older mice. Critically, an age-dependent analysis showed a progressive decline in the expression of CV-B3-binding Coxsackievirus and Adenovirus Receptor (CAR) splice variants (CAR1 and CAR2) at both the transcriptional and translational levels as the mice matured from 7 to 30 days. These receptor isoforms demonstrated a direct correlation with viral replication efficiency in younger hosts. Concurrently, aging was associated with a rise in non-binding CAR variants (CAR3 and CAR4). During CV-B3 infection, the abundance of CAR1/CAR2 in young mice facilitated accelerated viral proliferation, coupled with the hyperactivation of the NLRP3 inflammasome and the expansion of IL-17-producing γδT cells (γδT17 cells). This cascade triggered excessive production of proinflammatory cytokines (IL-1β, IL-18, and IL-17), culminating in pronounced inflammatory infiltrates within cardiac and cerebral tissues. These findings establish NLRP3 inflammasome dysregulation as a critical determinant of CV-B3-induced tissue damage and provide novel insights into the heightened susceptibility to CV-B infection during early life and its associated severe disease rates. Full article

Echovirus 18, a member of the B group of enteroviruses, is a significant etiological agent of aseptic meningitis and viral encephalitis in children. In this study, we investigated the pathogenicity of E18 by establishing a mouse infection model after comparing various mouse strains and injection methods. Two-day-old IFNAR1 knockout mice infected with clinical isolates of E18 exhibited symptoms such as lethargy, hind limb paralysis, and even mortality. Similarly, some two-day-old C57BL/6J mice displayed comparable symptoms; however, the incidence was lower than that observed in IFNAR1 knockout mice. No similar symptoms were noted in any Balb/c mice. Significant pathological changes were observed in skeletal muscle, brain tissue, and other organs of symptomatic mice; among these tissues, skeletal muscle demonstrated the highest viral load. The established infection model using two-day-old IFNAR1 knockout mice provides valuable insights into further investigations regarding its pathological injury mechanisms as well as the protective effects conferred by antibodies. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Viral infections may vary from mild to severe, manifesting with a wide range of symptoms, including skin lesions, influenza-like symptoms, or meningitis/meningoencephalitis signs. Viruses that cause both skin lesions and meningitis comprise, e.g., Enteroviruses (EVs) and Herpes viruses (HV). EVs are responsible for approximately 90% of viral meningitis cases. They occur frequently among children under 3 years of age and are characterized by various types of rash. HV infections are responsible for up to 18% of viral meningitis, mostly among adults or older children. Most patients with viral meningitis recover entirely. However, the rates of serious complications and mortality may be as high as 74% and 10%, respectively, for particularly vulnerable neonatal or immunocompromised patients. Patients that present signs of encephalitis and/or are suspected to have HSV/VZV infection require immediate implementation of empiric acyclovir therapy before receiving the polymerase chain reaction (PCR) test results. The clinical picture of viral meningitis may differ depending on the virus, including the presence of both meningeal signs and skin lesions. Therefore, early identification of the etiological factor is necessary for early and proper treatment implementation. It is crucial to accurately differentiate between the causative agents, and this work focuses on answering the question of how skin lesions can assist in achieving a better and faster diagnosis. The aim of this review was to analyze the characteristics of skin lesions in the course of meningitis caused by various viral species. This can be helpful for physicians in the diagnostic process and subsequent treatment. Full article

In the first 90 days, most meningitis cases are viral. Newborns often show nonspecific symptoms, making early diagnosis difficult but crucial for effective treatment and good outcomes. Cerebro-spinal fluid (CSF) analysis is the gold standard for diagnosis, enabling targeted therapy. We report on a newborn with rare viral meningitis due to herpes simplex virus type 1 and enterovirus coinfection. This uncommon situation complicates diagnostic and therapeutic management. We share our experience and review the limited literature on such neonatal viral coinfections. Full article

Case summary: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. A neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis; no infectious organisms were seen. Toxoplasma IgG/IgM and Cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. The cat was suspected to have feline infectious peritonitis, and to aid in clinical diagnosis he was enrolled in research study—with targeted Nanopore-based sequencing specifically identifying and characterizing FCoV-1 RNA in spinal fluid and anal swab, but not in urine. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remains ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces. Full article

Acute central nervous system (CNS) infections, such as meningitis and encephalitis, represent medical emergencies that require rapid identification of the causative pathogen to guide appropriate therapeutic interventions. The QIAstat-Dx^® Meningitis/Encephalitis (QIA/ME) is a molecular syndromic panel that enables the simultaneous detection of multiple pathogens and provides the visualization of cycle threshold (Ct) values, offering rapid results for prompt clinical management. This study retrospectively tested, with the QIA/ME panel, 170 cerebrospinal fluid (CSF) samples from patients with CNS infections, confirmed through routine diagnostic workflows. The results were compared with those obtained from bacterial culture and singleplex PCR for viral detection. The QIA/ME demonstrated 100% concordance with reference methods for bacterial and yeast infections. For viral infections, the overall detection rate was 85.9%. Specifically, when singleplex PCR results exceeded 250 copies/mL for DNA viruses and 500 copies/mL for the RNA virus, the concordance rate with the QIA/ME was 96.8%. In contrast, when PCR values were below these thresholds, the concordance rate dropped to 43.8%. A strong overall correlation was observed between the viral load measured by singleplex PCR and Ct values from the QIA/ME (ρ = −0.83, p < 0.001). Only for enterovirus a weak correlation was found (ρ = −0.40, p = 0.056). The QIA/ME panel is an effective diagnostic tool for viral CNS infections, allowing for the visualization of Ct values that reflect pathogen load in samples and which could be useful in guiding clinical decision-making and patient management. Full article

The transmission dynamics of many pathogens were altered during the coronavirus disease 2019 (COVID-19) pandemic. Several factors, including control measures and social distancing, have influenced the circulation and epidemiology of major etiological agents of meningitis during this period. This review examined trends in the primary etiologic agents of meningitis during and after the COVID-19 pandemic. A comprehensive literature search was conducted using the MEDLINE, Embase, LILACS, and SciELO databases for studies published between 2020 and 2024. The data were summarized descriptively and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty-eight studies are included in this review. Bacterial and viral meningitis pathogens exhibited significant epidemiological shifts during the pandemic. A marked decline in infections caused by the enteroviruses, Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae was observed from 2020 to 2021 in the northern and southern hemispheres during the pandemic. Post-pandemic, meningitis cases increased, with a resurgence in various countries. Despite the heterogeneity of the studies, the evidence indicates that the COVID-19 pandemic significantly affected the epidemiology of meningitis-causing microorganisms during and after the pandemic. Understanding these epidemiological shifts and dynamics is crucial for defining the control measures, vaccination strategies, and public health policies in the post-COVID-19 era. Full article

Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease’s symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV. Full article

Meningitis is an inflammation of the meninges that can sometimes be a life-threatening disease. Therefore, fast and proper diagnosis with the implementation of adequate treatment is crucial in its management. Treatment depends on etiology, which can be viral, bacterial, fungal, and parasitic. Diagnosis is based on thorough clinical examination with a performance of lumbar puncture in the case of meningitis suspicion. This procedure, however, remains invasive with several contraindications and a need for a patient’s consent, which is not always given due to the patient’s fear of it, for instance. Thus, this systematic review aimed to summarize the available literature on the topic of blood biomarkers in meningitis differentiation. A selection process was performed by two authors independently in accordance with the Preferred Research Items for Systematic Reviews and Meta-analyses. Two databases were screened. It led to the identification of 863 articles, of which 43 were eventually included in the systematic review. The analysis resulted in identifying blood biomarkers in both adult and pediatric meningitis. Most studies focused on inflammatory markers, such as C-reactive protein and procalcitonin, from which procalcitonin showed better utility. Among other analyzed molecules were, for instance, interleukins, apolipoproteins, and microRNAs. Moreover, many researchers suggested that combining biomarkers or implementing novel technologies may lead to the best accuracy. However, many suggested methods lack validation, which stands in the way of making them widely used. Full article

Introduction: Calcium homeostasis is essential for neurophysiological functions, with dysregulation implicated in neurodegenerative diseases. Recent studies suggest that specific viral brain infections, such as tick-borne encephalitis, can initiate neuronal loss and subsequent neurodegenerative changes. This study examines alterations in calcium levels within the cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE). Objectives: To evaluate the concentration of calcium in the CSF of TBE patients and assess its potential as a diagnostic marker for disease severity. Materials and Methods: CSF samples were collected from 42 subjects (11 controls, 20 with TBE, 11 with other forms of meningitis). Calcium levels were measured using the Alinity c analyzer. Statistical analyses included the Shapiro–Wilk test, Mann–Whitney U test, and ROC curve analysis. Results: Calcium levels were significantly lower in TBE patients compared to controls (mean 0.85 mmol/L vs. 0.98 mmol/L). Lower calcium levels were associated with milder cases of TBE. ROC analysis (AUC 0.802, p-value 0.0053) supports the diagnostic utility of calcium concentration in differentiating TBE severity. The optimal cut-off value for calcium was >3.09 mg/dL, with a sensitivity of 84.62% and specificity of 71.43%. These findings further emphasize the potential of calcium as a diagnostic marker for TBEV. Conclusions: The observed differences in CSF calcium levels between mild and severe TBE cases highlight its potential as a diagnostic marker. Further research is warranted to elucidate calcium’s role in TBE, aiming to improve clinical management and reduce complications. We emphasize that this study is one of the first to propose calcium levels as a potential biomarker for assessing the severity of tick-borne encephalitis, offering a new perspective in the diagnostic approach to this infection. Full article

Neurological disorders, some of which are associated with viral infections, are growing due to the aging and expanding population. Despite strong defenses of the central nervous system, some viruses have evolved ways to breach them, which often result in dire consequences. In this review, we recount the various ways by which different viruses can enter the CNS, and we describe the consequences of such invasions. Consequences may manifest as acute disease, such as encephalitis, meningitis, or result in long-term effects, such as neuromuscular dysfunction, as occurs in poliomyelitis. We discuss evidence for viral involvement in the causation of well-known chronic neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, as well as vascular dementia in the elderly. We also describe the approaches currently available to control a few of the neural viral infections. These include antivirals that are effective against human immunodeficiency virus and herpes simplex virus, as well as vaccines valuable for controlling rabies virus, poliomyelitis virus, and some flavivirus infections. There is an urgent need to better understand, at a molecular level, how viruses contribute to acute and, especially, chronic neurological diseases and to develop more precise and effective vaccines and therapies. Full article

Human enterovirus 71 (EV-A71), a member of the Picornaviridae family, is predominantly associated with hand, foot, and mouth disease in infants and young children. Additionally, EV-A71 can cause severe neurological complications, including aseptic meningitis, brainstem encephalitis, and fatalities. The molecular mechanisms underlying these symptoms are complex and involve the viral tissue tropism, evasion from the host immune responses, induction of the programmed cell death, and cytokine storms. This review article delves into the EV-A71 life cycle, with a particular emphasis on recent advancements in understanding the virion structure, tissue tropism, and the interplay between the virus and host regulatory networks during replication. The comprehensive review is expected to contribute to our understanding of EV-A71 pathogenesis and inform the development of antiviral therapies and vaccines. Full article

Neurological manifestations associated with human parvovirus B19 (B19V) infections are rare and varied. Acute encephalitis and encephalopathy are the most common, accounting for 38.8% of all neurological manifestations associated with human B19V. Herein, we report on the clinical features of 13 laboratory-confirmed human cases of B19V-associated encephalitis in Senegal in the framework of a hospital-based surveillance of acute viral encephalitis conducted from 2021 to 2023. Overall, B19V was detected from 13 cerebrospinal fluid samples using specific real time PCR. The mean age was 16.7 years among B19V-positive patients, with a higher prevalence in 0–5-year-old children and the sex ratio (male/female) was 2.25. The B19V-positive patients mainly exhibited hypoleukocytosis, normal glycorrhachia, and normal proteinorrachia in the cerebrospinal fluid. While the main neurological symptoms included meningeal and infectious syndromes. Furthermore, three complete B19V genome sequences were successfully characterized using next-generation sequencing. The newly characterized sequences belonged to the genotype 1a and represent, to date, the first complete B19V genome sequences from Senegal. These sequences could be useful not only in future phylodynamic studies of B19V but also in the development of prevention or treatment countermeasures. Our study is noteworthy for the identification of acute B19V-associated encephalitis in Senegal More investigations on the risk factors associated with B19V transmission in Africa are warranted. Full article