Search Results (200)

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

Rabies, a viral encephalitis caused by rabies virus (RABV), is 100% fatal upon the onset of symptoms. Effective post-exposure prophylaxis (PEP) measures are available, but they are often difficult to access in low-income countries. WHO estimates about 59,000 deaths due to rabies globally, and the majority are contributed by developing countries. Hence, developing drugs for the treatment of post-symptomatic rabies is an urgent and unmet demand. It is worth noting that previous efforts regarding antiviral strategies, such as small-interfering RNA, antibodies and small-molecule inhibitors, against the rabies virus have failed to show efficacy in pre-clinical studies, especially when the virus has reached the central nervous system (CNS). Therefore, drug repurposing seems to be an alternative tool for the development of new anti-rabies drugs. We validated and used a high-throughput, FITC-conjugated antibody-based flow cytometry assay to expedite the identification of repurposable new drug candidates against the RABV. The assay was validated using ribavirin and salinomycin as reference compounds, which showed EC50 values of 10.08 µM and 0.07 µM, respectively. We screened a SelleckChem library comprising 3035 FDA-approved compounds against RABV (CVS-11) at 10 µM concentration. Five compounds (clofazimine, tiamulin, difloxacin, harringtonine and homoharringtonine) were active against RABV, with greater than 90% inhibition. Homoharringtonine (HHT) identified in the present study is active against laboratory-adapted RABV (CVS-11) and clinical isolates of RABV, with an average EC50 of 0.3 µM in both BHK-21 and Neuro-2a cell lines and exhibits post-entry inhibition. Full article

Caprine arthritis and encephalitis (CAE), caused by small ruminant lentivirus (SRLV), is a key disease of goats, with chronic inflammation of joints and brain symptoms leading to losses in milk production and animal trade. In this study, we analyzed gene expressions in the milk somatic cells (MSCs) of seropositive (SRLV-SP) and seronegative (SRLV-SN) goats to identify transcriptomic changes using a non-invasive sampling method. Materials and Methods: This study was conducted on goats of two Polish breeds (Polish Improved White and Polish Improved Fawn), which were kept at the Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, during their first lactation. MSCs were isolated from milk, and gene expression was analyzed using the Goat Gene Expression Microarray. The results were verified by RT-qPCR for five genes (DUSP26, PRLR, SCARA3, APBB2, OR4F4). Statistical analysis was performed in GeneSpring 12 software. Results: Microarrays showed reduced expression of DUSP26, PRLR, SCARA3, APBB2, and OR4F4 genes in SRLV-SP goats. RT-qPCR confirmed changes for DUSP26, SCARA3, and APBB2. Functional analysis indicated associations with immune processes and HIV-like pathways. Discussion: The results suggest that SRLV induces transcriptomic perturbations, especially in immunity-related genes. MSCs are an effective model for non-invasive studies, and further studies may support strategies for combating CAE. Full article

While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p < 0.02); IL10 versus IL-12p70a (p < 0.02); IL-1b versus IL-6 (p < 0.01); MCP1 versus TARC (p < 0.03); IL-8 versus TARC (p < 0.002); and Eotaxin3 versus TARC (p < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (p < 0.01); TNF-α versus IL-1-β (p < 0.06); MCP4 versus TARC (p < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology. Full article

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

Small cell lung cancer (SCLC) is an aggressive form of lung cancer characterized by rapid growth and early metastases. As a neuroendocrine tumour, SCLC is especially notorious for various paraneoplastic syndromes, one of which is a rare neurological syndrome called paraneoplastic limbic encephalitis (PLE) that manifests with amnestic cognitive impairment and seizures. Here, we describe a case of a 53-year-old female who presented with neuropsychiatric symptoms of delusions, hallucinations, and cognitive impairment that started months prior to being diagnosed with extensive-stage SCLC. With no previous neuropsychiatric history, this raised the question of whether her presentation was related to PLE rather than a primary psychiatric condition, as initially diagnosed. Her symptoms improved with chemotherapy and radiation treatment of the underlying cancer, favouring a paraneoplastic etiology. Overall, this case underscores the importance of considering paraneoplastic syndromes in patients presenting with new neuropsychiatric symptoms, as early recognition and treatment can improve prognosis. Full article

Background/Objectives: Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare neurological disorder primarily affecting pediatric patients but also observed in adults. The radiological hallmark of MERS is a reversible lesion in the splenium of the corpus callosum. Although MERS generally has a favorable prognosis, its variable presentation poses diagnostic challenges. This study examines the clinical variability, diagnostic hurdles, and outcomes of pediatric MERS cases. Methods: Our retrospective study included 19 pediatric patients (11 female and 8 males with an average age of 8.41 years) diagnosed with MERS between 2016 and 2024. Clinical data, including demographic characteristics, prodromal symptoms, neurological features, MRI findings, laboratory results, treatments, and outcomes, were analyzed. Results: Among the 19 patients, 84% were previously healthy, with the remaining 16% having pre-existing medical conditions. The most common prodromal symptoms were fever (68%), vomiting (47%), and diarrhea (32%). Neurological manifestations included seizures (26%), headache (21%), and drowsiness (21%), among others. In terms of etiology, infections were identified in 52% of the patients, with viral agents, particularly rotavirus, being the most common (40%). Hyponatremia was present in 63% of the cohort. The typical MRI splenial lesion underwent complete resolution in all patients. Treatment varied, with 53% of patients receiving electrolyte rehydration, and 21% receiving intravenous immunoglobulin or corticosteroids. All patients, but one, achieved full recovery. Discussion: This study reinforces the clinical heterogeneity of MERS in pediatric patients, emphasizing its favorable prognosis independently of presentation. Viral infections and hyponatremia were the most frequent etiologies. 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

Background: Glioblastoma (GBM) is the most common primary brain tumor in adults, with a poor prognosis and survival. Although typically presenting with focal neurological deficits, seizures, or cognitive decline, GBM can occasionally mimic autoimmune encephalitis (AE), leading to significant diagnostic delay. The overlap in clinical, radiological, and serological findings between GBM and AE underscores the need for thorough evaluation. Methods: We retrospectively reviewed cases of patients diagnosed between 2016 and 2023 with pathology-confirmed GBM, critically rethinking those cases initially diagnosed with AE at symptom onset. The diagnostic workup included magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, autoantibody testing, and whole-body nuclear scanning to exclude extracranial malignancies. Results: We found five female patients diagnosed with GBM who initially presented with signs and symptoms suggestive for AE. Initial MRI showed non-specific brain tissue alterations, without definitive tumor features. CSF analysis was largely unremarkable, though some cases exhibited positive autoantibodies. Despite therapy, clinical deterioration and follow-up MRI revealed infiltrative intra-axial lesions with contrast enhancement, leading to pathology-confirmed GBM diagnoses. All patients had poor prognoses, with a mean survival of 10 ± 4 months. Conclusions: GBM can mimic AE, delaying appropriate treatment. In patients with atypical MRI findings and suboptimal response to therapy, early follow-up imaging and biopsy should be considered to exclude malignancy. A multidisciplinary approach is critical for timely diagnosis and improved management. Full article

In this report, we document and analyze a case in which the Irkut virus (IRKV) (Mononegavirales: Rhabdoviridae) caused a fatal human case following a bat bite in June 2021. Unfortunately, the available data did not permit a detailed taxonomic classification of the carrier bat (Chiroptera). The event occurred in the southwestern part of the Sikhote-Alin mountain region (Russian Far East) covered by the Ussuri taiga forest. The symptoms of the illness began with the following: fever; pronounced psychomotor and motor agitation; tremor of the lower jaw and tongue; aphasia; dyslexia; and dysphagia. These rapidly developed, leading to a severe and fatal encephalitis. The patient was not vaccinated for rabies and did not receive rabies immunoglobulin. Using brain sections prepared from the deceased, molecular diagnostics were performed: immunofluorescence (polyclonal anti-rabies immunoglobulin) indicating the presence of the lyssavirus antigen; and RT-PCR indicating traces of viral RNA. Sectional material (brain) was used for whole-genome sequencing, resulting in a near-complete sequence of the lyssavirus genome. The obtained genomic sequence was identified as the Irkut virus. A comparative analysis of the new sequence and other currently available IRKV sequences (NCBI) revealed differences. Specifically, amino acid differences between antigenic sites in the isolate and those of the rabies vaccine strain used regionally were noted. The patient history and subsequent analysis confirm human IRKV infection following bat contact. Like other fatal cases of IRKV infection described earlier, this case occurred in the southern part of the Russian Far East. Two have occurred in the southwestern part of the Sikhote-Alin mountain region. This indicates the possible existence of an active, natural viral focus. Full article

Antibodies against the NR1 or NR2 subunits of the NMDA receptor are linked to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, a type of encephalitis that mainly affects women. Clinicians who treat patients of all ages should be aware of this type of encephalitis since it may be a treatable differential for symptoms and indicators observed in neurology and psychiatric clinics. Auditory and visual hallucinations, delusions, altered behavior (often accompanied by agitation), reduced consciousness, motor disruption (from dyskinesia to catatonia), seizures, and autonomic dysfunction are typical clinical characteristics. In recent years, the incidence of autoimmune encephalitis diagnoses has markedly risen among adults, children, and adolescents. This fact is unequivocally connected to the dynamic evolution of novel diagnostic techniques and the advancement of medical knowledge. A specific variant of this illness is anti-NMDA receptor encephalitis. Psychiatrists frequently serve as the initial specialists to treat patients with this diagnosis, owing to the manifestation of psychiatric symptoms associated with the condition. The differential diagnosis is quite challenging and predominantly relies on the patient’s history and the manifestation of characteristic clinical signs. Given its high prevalence, anti-NMDA receptor encephalitis should be included in the differential diagnosis in routine psychiatric treatment. We provide an overview of the research on the condition, covering its prognosis, management, epidemiology, differential diagnosis, and clinical presentation. Full article

Limbic encephalitis (LE) associated with anti-LGI1 antibodies is an autoimmune disorder characterized by memory decline, behavioral changes, and temporal lobe epilepsy. Faciobrachial dystonic seizures (FBDS) are a hallmark symptom, often preceding cognitive and psychiatric issues. This report presents an 80-year-old male with LGI1 encephalitis, initially manifesting as FBDS. A lung adenocarcinoma was diagnosed two months after the onset of neurological symptoms. Clinical and paraclinical data, including MRI and [18]FDG PET imaging, are described. The patient responded to immunotherapy, including steroids and plasma exchange, along with tumor resection. Following treatment, neurological symptoms resolved, except for mild anxiety and apathy. Further research is needed to determine whether LGI1 encephalitis may occasionally have a paraneoplastic origin, potentially influencing screening and management strategies. Full article

With the increased availability of hybrid PET/MRI in recent years, this method is increasingly used for neuroimaging in clinical practice. It combines the advantages of MRI (including high-resolution imaging of intracerebral lesions and data provided from specialised MRI sequences) with the benefits of PET, which visualises functional alterations in the brain, as well as assesses the myelin quantity changes and the severity of inflammation. The use of PET/MRI may help to eliminate the limitations of MRI indicated in imaging demyelinating inflammatory diseases (such as low specificity in imaging demyelination and a weak correlation of findings with clinical symptoms), as well as insufficient sensitivity in detecting lesions present in encephalitis. In addition to supporting the diagnosis of encephalitis, PET/MRI facilitates monitoring of the disease course and assessing the treatment efficacy of inflammatory demyelinating diseases and encephalitis, as well as evaluating the risk of multiple sclerosis relapse. Further multi-centre longitudinal studies are necessary to assess the real clinical potential of PET/MRI among patients with inflammatory demyelination or encephalitis. In addition to MS and AIE, these studies should also include other inflammatory demyelinating diseases (ADEM, NMO, NMOSD, and MOGAD) as well as encephalitis of viral and parasitic aetiology. Full article

As a significant zoonotic disease, rabies poses substantial economic challenges for the livestock sector, highlighting the need for effective wildlife monitoring as part of a One Health approach. This study documents the first case of paralytic rabies in a lowland tapir (Tapirus terrestris) at the Guaycolec Wildlife Station in Formosa, Argentina. The 12-year-old male tapir exhibited neurological symptoms, including limb paralysis and dysphagia, leading to its death. The rabies virus was confirmed through direct immunofluorescence, virus isolation in BHK-21 cells, and molecular diagnostics via real-time RT-PCR and conventional PCR. Antigenic variant 3, associated with Desmodus rotundus, was identified. Histopathological examination revealed non-suppurative encephalitis with lymphocytic perivascular cuffs, neuronal vacuolization, and acidophilic intracytoplasmic inclusion bodies in the grey matter. This case underscores the importance of expanded surveillance for non-traditional hosts, as it demonstrates the potential for rabies transmission in changing environments. The findings highlight the need to maintain epidemiological surveillance systems at the wildlife–livestock–human interface and to develop targeted control strategies to mitigate the spread of rabies, particularly in areas where vampire bat populations are subject to anthropogenic pressures. Comprehensive monitoring and early detection are essential for effective rabies management in both wildlife and urban contexts. Full article

Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, which has high morbidity but low mortality rates in humans. The disease manifests in humans as high fever, headache, myalgia, arthralgia, photophobia, and, in some cases, meningitis and encephalitis. Additionally, a recent report suggests that OROV may cause fetal death, miscarriage, and microcephaly in newborns when women are infected during pregnancy, similar to the issues caused by the Zika virus (ZIKV), another mosquito-borne disease in the same regions. OROV was first reported in the mid-20th century in the Amazon basin. Since then, over 30 epidemics and more than 500,000 infection cases have been reported. The actual case numbers may be much higher due to frequent misdiagnosis, as OROV infection presents similar clinical symptoms to other co-circulating viruses, such as dengue virus (DENV), chikungunya virus (CHIKV), ZIKV, and West Nile virus (WNV). Due to climate change, increased travel, and urbanization, OROV infections have occurred at an increasing pace and have spread to new regions, with the potential to reach North America. According to the World Health Organization (WHO), over 10,000 cases were reported in 2024, including in areas where it was not previously detected. There is an urgent need to develop vaccines, antivirals, and specific diagnostic tools for OROV diseases. However, little is known about this surging virus, and no specific treatments or vaccines are available. In this article, we review the most recent progress in understanding virology, transmission, pathogenesis, diagnosis, host–vector dynamics, and antiviral vaccine development for OROV, and provide implications for future research directions. Full article