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Emerging Microbes & Infections Dec 2023Systemic infection with , a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis,...
Systemic infection with , a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of virulence cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed cells was found to facilitate the host immunological defence against infection with wild-type . Further investigation demonstrated that cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.
Topics: Animals; Mice; Hot Temperature; Cryptococcosis; Cryptococcus neoformans; Vaccination; Immunization
PubMed: 37526401
DOI: 10.1080/22221751.2023.2244087 -
Acta Medica Portuguesa Sep 2023Behçet's disease is a relapsing multisystemic inflammatory syndrome characterized by recurrent oral and/or genital ulcers, uveitis, arthritis, skin lesions, and... (Review)
Review
Behçet's disease is a relapsing multisystemic inflammatory syndrome characterized by recurrent oral and/or genital ulcers, uveitis, arthritis, skin lesions, and gastrointestinal and neurological involvement. Neuro-Behçet corresponds to nervous system involvement and is one of the most severe complications of Behçet disease. It occurs in 3% to 30% of cases and is categorized into parenchymal (most common) or non-parenchymal disease. The most common manifestation of parenchymal neuro-Behçet is meningoencephalitis with involvement of the brainstem, where patients present with cranial neuropathies, encephalopathy, sensory-motor syndromes, epilepsy, or myelitis. The main non-parenchymal manifestation is cerebral venous thrombosis. Neuro-Behçet has a predominantly subacute course, with remission within weeks, or clinical progression in one third of the cases. The diagnosis is essentially clinical and diagnostic tests help to corroborate the suspicion, distinguish from differential diagnoses, and exclude complications. Brain magnetic resonance imaging allows the identification of acute lesions (hypointense or isointense on T2-weighted and hypointense on T1-weighted sequences) contrast-enhanced, and chronic lesions characterized by non-contrast enhanced small lesions and brainstem atrophy. If non-parenchymal involvement is suspected, cerebral veno-magnetic resonance imaging /computed tomography should be performed. Cerebrospinal fluid shows elevated proteinorachia and pleocytosis in parenchymal and no changes in non-parenchymal neuro-Behçet (except increased opening pressure). Outbursts of parenchymal disease should be treated with high dose intravenous corticosteroid therapy, with subsequent switch to oral corticoids, followed by biologic therapy, usually an anti-TNF. The treatment of cerebral venous thrombosis is controversial and may consist of a combination of corticosteroids and anticoagulation.
Topics: Humans; Behcet Syndrome; Tumor Necrosis Factor Inhibitors; Brain; Magnetic Resonance Imaging; Diagnosis, Differential; Adrenal Cortex Hormones; Venous Thrombosis
PubMed: 37345389
DOI: 10.20344/amp.19734 -
Brain Sciences Sep 2023Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are... (Review)
Review
Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.
PubMed: 37759952
DOI: 10.3390/brainsci13091351 -
European Journal of Pediatrics Oct 2023Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA...
UNLABELLED
Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA received an increase in reports of PeV infections among infants. A retrospective cohort study describing the clinical characteristics and outcomes of PeV encephalitis in infants aged < 90 days. Rates of PeV encephalitis were determined based on the number of PeV encephalitis cases out of all meningoencephalitis multiplex polymerase chain reaction panel (MEP) obtained among infants aged < 90 days per year. Out of 2115 infants evaluated for meningoencephalitis, 32 (1.5%) cases of PeV encephalitis were identified. All cases had an absence of pleocytosis and normal protein and glucose levels on CSF analysis. Half of the cases presented with a symptomatic triad (fever, rash, and fussiness). More than one-third of cases (39%) presented with a sepsis-like syndrome, 13% presented with seizures, and 25% were admitted to the pediatric intensive care unit (PICU). MRI of the brain was obtained in four of the cases presented with seizure, all of which demonstrated characteristic radiological findings of the periventricular white matter with frontoparietal predominance and involving the corpus callosum, thalami, and internal and external capsules. Rates of PeV encephalitis varied from year to year, with the highest rates in 2018 and 2022. PeV was the second most detected pathogen in MEP in both 2018 and 2022, and the fifth most detected pathogen in all positive MEP during the study period 2017-2022.
CONCLUSION
PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks.
WHAT IS KNOWN
• PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days. • Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization.. • Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years..
WHAT IS NEW
• Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis. • Knowledge of the biennial seasonality pattern in PeV infection. • PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.
Topics: Child; Infant; Humans; Parechovirus; Picornaviridae Infections; Retrospective Studies; Meningoencephalitis; Seizures; Sepsis
PubMed: 37490108
DOI: 10.1007/s00431-023-05117-7 -
Acta Neuropathologica Feb 2024Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease...
Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8/perforin/granzyme A/B cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.
Topics: Humans; Animals; Dogs; Glial Fibrillary Acidic Protein; Encephalomyelitis; Astrocytes; Autoimmune Diseases of the Nervous System; Meningoencephalitis; Autoantibodies
PubMed: 38310187
DOI: 10.1007/s00401-023-02678-7 -
Current Opinion in Neurology Jun 2024Immune checkpoint inhibitors (ICI) may trigger immune-related adverse events which rarely affect the central nervous system (CNS-irAEs). Over the past few years,... (Review)
Review
PURPOSE OF REVIEW
Immune checkpoint inhibitors (ICI) may trigger immune-related adverse events which rarely affect the central nervous system (CNS-irAEs). Over the past few years, cumulative data have led to the characterization of well defined syndromes with distinct cancer and antibody associations as well as different outcomes.
RECENT FINDINGS
The most frequent CNS-irAE is encephalitis, which includes three main groups: meningoencephalitis, a nonfocal syndrome usually responsive to corticosteroids; limbic encephalitis, associated with high-risk paraneoplastic neurological syndromes (PNS) antibodies (e.g. anti-Hu, anti-Ma2) and neuroendocrine cancers, characterized by poor treatment response and outcomes; and cerebellar ataxia, with variable outcomes (worse when high-risk PNS antibodies are detected). Additionally, a diffuse encephalopathy without inflammatory findings, with poor response to corticosteroids and high mortality has been described. The spectrum of CNS-irAEs also includes meningitis, myelitis, and rarer presentations. A subset of CNS-irAEs (i.e. limbic encephalitis and/or rapidly progressive cerebellar ataxia) is undistinguishable from ICI-naïve PNS.
SUMMARY
The clinical and outcomes diversity of CNS-irAEs suggests different pathogenic mechanisms, which need to be understood to establish more effective and specific treatment modalities. It is crucial to identify biomarkers able to predict which patients will experience severe CNS-irAEs, to anticipate their diagnosis, and to predict long-term outcomes.
Topics: Humans; Immune Checkpoint Inhibitors; Central Nervous System Diseases; Neoplasms
PubMed: 38483130
DOI: 10.1097/WCO.0000000000001259 -
Annals of Medicine Dec 2023Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges... (Review)
Review
Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased. At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population. The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss. Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients.
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Brain; Meningoencephalitis; China
PubMed: 36598144
DOI: 10.1080/07853890.2022.2164348 -
Journal of Veterinary Diagnostic... Sep 2023Two adult mixed-breed ewes were presented with a 2-wk history of upper respiratory disease. Both animals were depressed, with bilateral serosanguineous nasal discharge...
Two adult mixed-breed ewes were presented with a 2-wk history of upper respiratory disease. Both animals were depressed, with bilateral serosanguineous nasal discharge and harsh bronchovesicular sounds accompanied by crackles and wheezes on auscultation. One animal was recumbent and was euthanized at presentation. The other animal with similar signs, as well as exophthalmos, was euthanized because of a mass in the nasal passages. On autopsy, severe pyogranulomatous and necrotizing ethmoidal rhinitis with focal pyogranulomatous pneumonia was diagnosed in both animals. An intralesional fungal organism was identified in the nares and lungs of both animals. The organism could not be isolated via fungal culture but was identified as sp. by a PCR assay. spp. are rarely associated with disease in veterinary medicine. This ubiquitous fungus might cause disease following trauma to the nasal passages or secondary to immunocompromise.
Topics: Female; Animals; Sheep; Trichosporonosis; Lung; Pneumonia; Trichosporon; Sheep Diseases
PubMed: 37387318
DOI: 10.1177/10406387231185568 -
Neurology(R) Neuroimmunology &... Nov 2023Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and...
OBJECTIVES
Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and encephalitis. In this study, we report a case of chronic enterovirus meningoencephalitis in prolonged B-cell depletion years after rituximab therapy.
METHODS
This is a case report from a German academic hospital. In addition to repeated clinical examinations, repeated brain MRI and extended CSF and laboratory diagnostics were performed. We used the CARE checklist when writing our report.
RESULTS
A 38-year-old man presented with high fever (>40°C), severe headache, and progressive neurologic and cognitive deficits. As result of previous lymphoma therapy with rituximab years ago, prolonged B-cell aplasia was detected. To restore humoral immunity, the patient received repeated infusions of immunoglobulins. In the end, a complete restitution of the physical and mental condition was achieved with the established therapy.
DISCUSSION
This case report should emphasize the importance of assessing humoral immunity even years after B-cell depletion therapy, especially in case of opportunistic infections.
Topics: Male; Humans; Adult; Rituximab; Enterovirus; Enterovirus Infections; Meningoencephalitis; B-Lymphocytes
PubMed: 37813597
DOI: 10.1212/NXI.0000000000200171 -
Journal of Neuroimmunology Sep 2023Shikonin is an anti-inflammatory natural herbal drug extracted from Lithospermum erythrorhizon and its therapeutic effect on neuropsychiatric systemic lupus...
Shikonin is an anti-inflammatory natural herbal drug extracted from Lithospermum erythrorhizon and its therapeutic effect on neuropsychiatric systemic lupus erythematosus (NPSLE) is yet unknown. In our study, Shikonin significantly reversed the cognitive impairment and alleviated the brain tissue damage in NPSLE mice. The permeability of blood-brain barrier was also verified to be repaired in Shikonin-treated NPSLE mice. In particular, we found that Shikonin alleviated neuroinflammation through inhibiting β-catenin signaling pathway, thereby depressing the activation of microglia and the loss of neuronal synapses. Overall, Shikonin may be a promising candidate drug for NPSLE through diminishing neuroinflammation and repairing neuron damage.
Topics: Animals; Mice; Lupus Vasculitis, Central Nervous System; Lupus Erythematosus, Systemic; Neuroinflammatory Diseases; Cognitive Dysfunction; Neurons; Anti-Inflammatory Agents
PubMed: 37536051
DOI: 10.1016/j.jneuroim.2023.578166