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Santosh-Gupta

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EncephalitisAbstracts

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NeuroHIV and use of addictive substances.

In the past three decades, substance abuse has been identified as a key comorbidity of human immunodeficiency virus-1 (HIV-1) infection. Many studies have found that the use and abuse of addictive substances hastens the progression of HIV-1 infection and HIV-associated neurocognitive disorders. Advances in highly active antiretroviral therapy (HAART) in the mid-1990s have been successful in limiting the HIV-1 viral load and maintaining a relatively healthy immune response, allowing the life expectancy of patients infected with HIV to approach that of the general population. However, even with HAART, HIV-1 viral proteins are still expressed and eradication of the virus, particularly in the brain, the key reservoir organ, does not occur. In the post-HAART era, the clinical challenge in the treatment of HIV infection is inflammation of the central nervous system (CNS) and its subsequent neurological disorders. To date, various explicit and implicit connections have been identified between the neuronal circuitry involved in immune responses and brain regions affected by and implicated in substance abuse. This chapter discusses past and current medical uses of prototypical substances of abuse, including morphine, alcohol, cocaine, methamphetamine, marijuana, and nicotine, and the evidence that systemic infections, particularly HIV-1 infection, cause neurological dysfunction as a result of inflammation in the CNS, which can increase the risk of substance abuse.

International review of neurobiology

2162-5514

2014

10.1016/B978-0-12-801284-0.00013-0

Zika Virus Disease for the Neurointensivist.

Zika virus (ZIKV) is a mosquito-borne and sexually transmitted flavivirus currently spreading throughout the Pacific and Western Hemisphere. ZIKV infection is often either asymptomatic or causes a self-limiting illness with symptoms such as rash, fever, myalgia, arthralgia, headache, or conjunctivitis. Rarely, ZIKV infection has been associated with conditions such as severe thrombocytopenia, microcephaly and other developmental abnormalities, acute polyneuropathy/Guillain-Barré syndrome, myelitis, meningoencephalitis, transient encephalopathy, provoked seizures, and various ophthalmologic conditions. Optimal treatment of these ZIKV-associated conditions is currently unclear and is largely guided by expert opinion or case reports/series. Further studies are needed to establish best treatment practices. This review concentrates on caring by neurointensivists for the patient affected with Zika virus-expected to flare up again in the summer.

Neurocritical care

1556-0961

2017

10.1007/s12028-016-0333-z

A community-based prospective cohort study of dengue viral infection in Malaysia: the study protocol.

Globally, dengue infections constitute a significant public health burden. In recent decades, Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes. The cyclical dominance of sub-types contributes to a pattern of major outbreaks. The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths. Understanding the complex interaction of the dengue virus, its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem.

Infectious diseases of poverty

2049-9957

2016

10.1186/s40249-016-0172-3

Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.

Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.

Virology

1096-0341

2014

10.1016/j.virol.2013.11.008

Paraneoplastic encephalomyeloradiculits with multiple autoantibodies against ITPR-1, GFAP and MOG: case report and literature review.

Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies.

Neurological research and practice

2524-3489

2021

10.1186/s42466-021-00145-w

Acute childhood encephalitis and Mycoplasma pneumoniae.

In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

1058-4838

2001

10.1086/320748

Encephalomyelitis Caused by <i>Balamuthia mandrillaris</i> in a Woman With Breast Cancer: A Case Report and Review of the Literature.

<i>Balamuthia mandrillaris</i> is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of <i>Balamuthia</i> GAE is difficult because symptoms are non-specific. Here, we report a case of <i>Balamuthia</i> amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a <i>Mycobacterium abscessus</i> infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed <i>B. mandrillaris</i>, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.

Frontiers in immunology

1664-3224

2021

10.3389/fimmu.2021.768065

Glutamate receptor antagonists protect from virus-induced neural degeneration.

Neuronal damage during acute viral encephalomyelitis can result directly from virus infection or indirectly from the host immune response to infection. In neurodegenerative diseases and stroke, neuronal death also can result from excess release of excitatory amino acid neurotransmitters, such as glutamate. To determine the role of glutamate excitotoxicity in fatal alphavirus-induced paralytic encephalomyelitis, we treated mice infected with neuroadapted Sindbis virus (NSV) with antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtypes of glutamate receptors. Both apoptotic and necrotic neurons in the hippocampus were decreased in animals treated with MK-801, an NMDA receptor antagonist, or GYKI-52466, an AMPA receptor antagonist. However, only AMPA receptor blockade prevented damage to spinal cord motor neurons and protected mice from paralysis and death due to NSV infection. Protection was not caused by altered virus replication because treatment did not affect virus distribution and actually delayed virus clearance. These results provide evidence that NSV infection activates neurotoxic pathways that result in aberrant glutamate receptor stimulation and neuronal damage. Furthermore, AMPA receptor-mediated motor neuron death is an important contributor to paralysis and mortality in acute alphavirus-induced encephalomyelitis.

Annals of neurology

0364-5134

2004

10.1002/ana.20033

Rapidly progressive encephalopathy caused by Coxsackie meningoencephalitis in an elderly male.

Enteroviruses and Coxsackie viruses are common causes of aseptic meningitis and encephalitis in children. These infections usually have a benign, self-limited course. However, they can have a florid presentation in immunocompromised patients, such as neonates, patients exposed to immunosuppressive drugs, such as transplant recipients and patients with agammaglobulinemia. We present a rare case of rapidly progressive acute encephalopathy caused by Coxsackie meningoencephalitis and complicated by refractory status epilepticus in an immunocompetent adult male. Our case highlights the importance of having a broad differential in patients presenting with rapidly progressive acute encephalopathy. Although rare, an enterovirus infection caused by a Coxsackie virus subtype can have a severe presentation causing significant morbidity. This case, also underscores the importance of searching for underlying immunodeficiency in malignant presentations of common viral infections. Hence, rapidly progressive acute encephalopathy due to coxsackievirus can occur in immunocompetent individuals. Aggressive and systematic diagnostic and therapeutic approach in such severe cases can influence overall outcomes.

Journal of neurovirology

1538-2443

2018

10.1007/s13365-018-0676-7

FCD Type II and mTOR pathway: Evidence for different mechanisms involved in the pathogenesis of dysmorphic neurons.

Type II focal cortical dysplasia (FCD II) is a malformation of cortical development, frequently associated with intractable epilepsy, characterised by cortical dyslamination, dysmorphic neurons (DNs) and balloon cells (BCs). We investigated the expression of pS6 (downstream target) and pPDK1-pAkt (upstream targets) as evidence for mTOR pathway activation and their co-expression with Interleukin-1β in FCD II surgical specimens and compared the findings with control non-epileptic tissue, non-malformed epileptic tissue or acquired epilepsy-Rasmussen's Encephalitis (RE) occasionally presenting pS6 and Interleukin-1β positive abnormal neurons. Downstream mTOR activation was demonstrated in almost all abnormal cells in both FCD II and RE. Conversely, upstream activation in FCD II was observed in the majority of BCs, in a proportion of DNs, not presenting Interleukin-1β expression, but not at all in RE scattered abnormal neurons. Based on these findings we suggest that the presence of BCs and DNs in FCD II could be due to a first upstream mTOR pathway PI3K-Akt-mediate event occurring very early during cortical development in the large proportion of abnormal cells; followed by the appearance of additional pS6 positive DNs promoted by the presence of a later inflammatory processes.

Epilepsy research

1872-6844

2017

10.1016/j.eplepsyres.2016.12.002

Presence of rabies specific immune complexes in cerebro-spinal fluid can help in ante-mortem diagnosis of human paralytic rabies.

Human rabies presents in two clinical forms, viz. furious or encephalitic and paralytic. Clinical diagnosis of paralytic form is difficult and requires laboratory confirmation. Presently available diagnostic techniques are not very sensitive for ante-mortem confirmation of rabies.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

1386-6532

2006

10.1016/j.jcv.2006.06.010

[Encephalitis due to the Epstein-Barr virus: a description of a clinical case and review of the literature].

INTRODUCTION. Infection by the Epstein-Barr virus (EBV) -either as a primary infection, a reactivation or an active chronic infection- can give rise to several clinical forms of involvement of the central nervous system. We report a case of encephalitis due to EBV produced by viral reactivation in an immunocompetent patient which initially mimicked, from the clinical and electroencephalographic point of view, encephalitis due to type 1 herpes simplex virus (HSV-1). CASE REPORT. A 51-year-old male who had reported the presence of dorsal herpes zoster some days earlier. The patient visited the emergency department after suffering a holocranial oppressive headache and febricula for seven days; 24 hours before admission to hospital, he was suffering from drowsiness and language disorder. The neurological examination revealed stiffness in the back of the neck and dysphasia. An analysis of the cerebrospinal fluid revealed pleocytosis (422 cells/mm(3)) with 98% of mononuclear cells and normal protein and glucose concentration levels in cerebrospinal fluid. Magnetic resonance imaging of the brain and electroencephalogram readings were normal with periodic lateralised epileptiform discharges in the left temporal region. Intravenous acyclovir treatment was initiated, but renal failure meant it had to be changed to oral valaciclovir with clinical resolution and improvement of the liquoral parameters. Polymerase chain reaction in the cerebrospinal fluid was positive for EBV and negative for the other neurotropic viruses. In blood, the serology test for EBV with IgG was positive, while IgM and heterophile antibody tests were negative. CONCLUSIONS. EBV infection can give rise to acute disseminated encephalomyelitis or affect several locations in the central nervous system, especially the cerebellum. Clinical pictures mimicking HSV-1 are less frequent. When encephalitis is related to viral reactivation, precipitating factors can be detected, as in our case.

Revista de neurologia

1576-6578

2013

No DOI available

[Case of inflammatory vasculopathy and encephalopathy caused by treatment with tacrolimus].

The case of inflammatory vasculopathy and encephalopathy caused by treatment with tacrolimus is reported. This 49-year-old woman developed progressive gait ataxia and right-sided hemiparesis after 7 years of tacrolimus therapy for focal sclerosing glomerulonephritis. MRI presented multifocal cerebral lesions with contrast enhancement. Oligoclonal banding was positive. When the treatment with tacrolimus was stopped, the clinical symptoms resolved completely and the MRI findings improved with corticoid monotherapy.

Der Nervenarzt

1433-0407

2005

10.1007/s00115-004-1744-1

[Clinical course of recovery from cognitive dysfunction in a patient with anti-N-methyl-D-aspartate receptor encephalitis].

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder, which occurs commonly in young women and is often associated with ovarian teratomas. We report the case of a patient with this disease, who exhibited cognitive deficits, and describe the clinical course of recovery from cognitive dysfunction. A 29-year-old right-handed woman suffered from chills and fever for 7 days prior to admission to hospital, and complained that she could not understand the content of TV programs. Following admission to hospital, she was found to have an ovarian teratoma and underwent oophorectomy. She was diagnosed with anti-NMDA receptor encephalitis based on the presence of antibodies in the serum and cerebrospinal fluid. She subsequently experienced phases with disturbance of consciousness and involuntary movement, and then moved into the gradual recovery phase 3 months after onset. Cerebral SPECT revealed a left-dominant decrease of blood flow in the prefrontal regions bilaterally. Neuropsychological examination 3 months after onset revealed frontal lobe syndrome comprising executive dysfunction, decreased spontaneity, and environmental dependency in addition to recent memory deficits. Approximately 6 months after onset, recent memory impairments and environmental dependency were resolved, and a gradual improvement in spontaneity and executive function was seen. One year after onset, the patient had regained independence and ability to self-care, and returned to her workplace. Our observations suggest that patients with anti-NMDA receptor encephalitis may recover from frontal lobe syndrome, including executive dysfunction and decreased spontaneity, slower than patients with other cognitive dysfunctions do.

Brain and nerve = Shinkei kenkyu no shinpo

1881-6096

2014

10.11477/mf.1416200013

Punctate lesion pattern suggestive of perivascular inflammation in acute natalizumab-associated progressive multifocal leukoencephalopathy: productive JC virus infection or preclinical PML-IRIS manifestation?

No abstract available

Journal of neurology, neurosurgery, and psychiatry

1468-330X

2013

10.1136/jnnp-2013-304986

Reversible myoclonus-ataxia encephalitis related to anti-mGLUR1 autoantibodies.

No abstract available

Movement disorders : official journal of the Movement Disorder Society

1531-8257

2019

10.1002/mds.27634

Acute urinary retention in a 23-year-old woman with mild encephalopathy with a reversible splenial lesion: a case report.

Patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion present with relatively mild central nervous system disturbances. Although the exact etiology of the condition remains poorly understood, it is thought to be associated with infective agents. We present a case of a patient with mild encephalitis/encephalopathy with a reversible splenial lesion, who had the unusual feature of acute urinary retention.

Journal of medical case reports

1752-1947

2011

10.1186/1752-1947-5-159

Intracranial administration of P gene siRNA protects mice from lethal Chandipura virus encephalitis.

In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55-75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated.

PloS one

1932-6203

2010

10.1371/journal.pone.0008615

Non-convulsive status epilepticus associated with glutamic acid decarboxylase antibody.

Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis. 

Clinical EEG and neuroscience

1550-0594

2013

10.1177/1550059412459330

Utilization of complement-dependent cytotoxicity to measure low levels of antibodies: application to nonstructural protein 1 in a model of Japanese encephalitis virus.

Enzyme-linked immunosorbent assay (ELISA) and related assays are representative of methods currently used for antibody tests. However, they occasionally produce nonspecific reactions, thus making it difficult to reliably measure low levels of specific antibodies. To find a test method that minimizes nonspecific reactions, we introduced the principle of antibody-mediated complement-dependent cytotoxicity (CDC) into an antibody assay. The procedure has three steps: (i) the mixing of test samples with a suspension of cells expressing the antigen of interest on their surfaces, (ii) the addition of rabbit complement, and (iii) the measurement of lactose dehydrogenase (LDH) activities by adding a chromogenic substrate to the reaction mixture. When the specific antibodies exist in the sample, complement activation triggered by antibody binding on the surface of the antigen-expressing cells may lyse the cells, releasing LDH into the medium. Mouse and rabbit sera hyperimmune to nonstructural protein 1 (NS1) of Japanese encephalitis virus (JEV) lysed NS1-expressing cells in a dose-dependent manner. Evaluations using sera from horses naturally infected with JEV showed that the CDC assay had quantitative correlation and qualitative agreement with previously established NS1 antibody-detecting immunostaining and ELISA methods. The assay method also detected NS1 antibodies in sera of mice 2 days after experimental infection with JEV; specific, but not natural, immunoglobulin M antibodies were detected. Since almost all sera examined in this study showed no nonspecific reactions, the CDC assay was shown to be a reliable method for measuring low levels of specific antibodies.

Clinical and vaccine immunology : CVI

1556-679X

2008

10.1128/CVI.00347-07

Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions.

Endothelial cells represent the first biological barrier for compounds, including nanoparticles, administered via the intravascular route. In the case of ischemic stroke and other vascular diseases, the endothelium overexpresses specific markers, which can be used as molecular targets to facilitate drug delivery and imaging. However, targeting these markers can be quite challenging due to the presence of blood flow and the associated hydrodynamic forces, reducing the likelihood of adhesion to the vessel wall. To overcome these challenges, various parameters including size, shape, charge or ligand coating have been explored to increase the targeting efficiency. Geometric shape can modulate nanoparticle binding to the cell, especially by counteracting part of the hydrodynamic forces of the bloodstream encountered by the classical spherical shape. In this study, the binding affinity of polystyrene nanoparticles with two different shapes, spherical and rod-shaped, were compared. First, vascular adhesion molecule-1 (VCAM-1) was evaluated as a vascular target of inflammation, induced by lipopolysaccharide (LPS) stimulation. To evaluate the effect of nanoparticle shape on particle adhesion, nanoparticles were coated with anti-VCAM-1 and tested under static conditions in cell culture dishes coated with cerebral microvasculature cells (bEnd.3) and under dynamic flow conditions in microfluidic channels lined with hCMEC/D3 cells. Effect of particle shape on accumulation was also assessed in two in vivo models including systemic inflammation and local brain inflammation. The elongated rod-shaped particles demonstrated greater binding ability in vitro, reaching a 2.5-fold increase in the accumulation for static cultures and 1.5-fold for flow conditions. Anti-VCAM-1 coated rods exhibited a 3.5-fold increase in the brain accumulation compared to control rods. These results suggest shape offers a useful parameter in future design of drug delivery nanosystems or contrast agents for neurovascular pathologies.

Journal of controlled release : official journal of the Controlled Release Society

1873-4995

2019

10.1016/j.jconrel.2019.07.026

Peritoneal dialysis improves quality-of-life in a left ventricular assist device destination therapy patient-a case report.

Progressive renal insufficiency is frequent in heart failure patients with a left ventricular assist device (LVAD). The optimal strategy for long-term dialysis in LVAD patients and its effect on quality-of-life in these patients remain to be determined.

European heart journal. Case reports

2514-2119

2021

10.1093/ehjcr/ytab307

Progressive multifocal leukoencephalopathy in a patient with Franklin disease and hypogammaglobulinemia.

We report an association between histologically confirmed progressive multifocal leukoencephalopathy (PML) and an extremely rare humoral immunodeficiency disease, Franklin disease. In our patient, clinical presentation has been typical and prompted us, together with radiological findings, to perform a brain biopsy to confirm the diagnosis even if there was no evidence of any other risk factor except hypogammaglobulinemia. We suggest that PML should be suspected in patients in whom immunosuppression is not obvious (i.e. not only in the setting of HIV infection or disseminated end-stage lymphomas) and involves defects in humoral immunity.

Journal of the neurological sciences

1878-5883

2009

10.1016/j.jns.2009.04.035

Mosquito (Diptera: Culicidae) fauna in an area endemic for West Nile virus.

Mosquito collections with CDC light traps using dry ice and pigeon-baited traps were carried out in south Moravia (Czech Republic) from April to October in 2007 and 2008 at two study sites. In 2007, 11 two-day captures were carried out in two-week intervals, and 1,490 female mosquitoes of nine species were caught. In 2008, 15 two-day trappings of mosquitoes were carried out: 6,778 females of 22 species of mosquitoes were trapped. The results showed marked differences in abundance and species composition of mosquitoes between both study sites and between the trapping methods. In the floodplain forest ecosystem of the Soutok study area, Aedes vexans predominated. The species composition in the Nesyt study site was more varied and the most common species was Culex pipiens. At the latter study site, Anopheles hyrcanus (var. pseudopictus) and Uranotaenia unguiculata, mosquito species with largely southern Eurasian distribution, were repeatedly demonstrated. The largest capture of mosquitoes was in traps with CO2 placed at a height 1 m above the ground. The capture of mosquitoes in the pigeon-baited traps as well as in the traps with CO2 placed in the canopy of trees was markedly lower in both study sites, with the predominant species being Culex pipiens.

Journal of vector ecology : journal of the Society for Vector Ecology

1948-7134

2010

10.1111/j.1948-7134.2010.00042.x

[A case of acute encephalitis with refractory repetitive partial seizures successfully controlled by very-high-dose phenobarbital therapy found in a boy].

We experienced a case of acute encephalitis with refractory, repetitive partial seizures (AERRPS) found in an 8-year-old boy. Convulsive status epilepticus developed at the onset, which was intractable to the treatment with intravenous thiopental sodium even at the maximum dose of 9 mg/kg/hr. Since the adverse effect developed, thiopental sodium was discontinued. Phenobarbital (PB) was administrated at a very high daily dose up to 80 mg/kg, reaching serum trough level of 250 μg/ml, which was markedly effective to the treatment. Because seizures reappeared during tapering the dosage of PB, potassium bromide (KBr) at a daily dose of 80 mg/kg was additionally administrated. PB was successfully tapered into a daily dose of 20 mg/kg with a trough serum level around 80 μg/ml. He recovered in motor functions, but had disturbance of memory and apneic seizures. A very-high-dose PB therapy in an early period may be helpful for the treatment of intractable convulsive status epilepticus.

No to hattatsu = Brain and development

0029-0831

2014

No DOI available

Impact of drought on vector-borne diseases--how does one manage the risk?

This article aimed to review all literature on drought and vector-borne disease to enable an assessment of the possible impact of drought on the changing risk of vector-borne diseases in the UK.

Public health

1476-5616

2014

10.1016/j.puhe.2013.09.006

Basic Analysis of the Cerebrospinal Fluid: An Important Framework for Laboratory Diagnostics of the Impairment of the Central Nervous System.

Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases of either infectious or non-infectious CNS involvement. Neutrophils are effector cells of innate immunity. Predominance of neutrophils was found in 98.2% of patients with purulent inflammation in CNS. Lymphocytes are cellular substrate of adaptive immunity. We found their predominance in 94.8% of patients with multiple sclerosis (MS), 66.7% of patients with tick-borne encephalitis (TBE), 92.2% of patients with neuroborreliosis, 83.3% of patients with inflammatory response with oxidative burst of macrophages in CNS and 75.0% of patients with malignant infiltration of meninges (MIM). The simultaneous assessment of aerobic and anaerobic metabolism in CSF using the coefficient of energy balance (KEB) allows us to specify the type of inflammation in CNS. We found predominantly aerobic metabolism (KEB > 28.0) in 100.0% CSF of patients with normal CSF findings and in 92.8% CSF of patients with MS. Predominant faintly anaerobic metabolism (28.0 > KEB > 20.0) in CSF was found in 71.8% patients with TBE and in 64.7% patients with neuroborreliosis. Strong anaerobic metabolism (KEB < 10.0) was found in the CSF of 99.1% patients with purulent inflammation, 100.0% patients with inflammatory response with oxidative burst of macrophages and in 80.6% patients with MIM. Joint evaluation of basic CSF parameters provides sufficient information about the immune response in the CSF compartment for rapid and reliable diagnosis of CNS involvement.

Current issues in molecular biology

1467-3045

2022

10.3390/cimb44080251

The human and animal health impacts of introduction and spread of an exotic strain of West Nile virus in Australia.

Vector-borne diseases can have substantial impacts on human and animal health, including major epidemics. West Nile virus (WNV) is of particular international importance due to its recent emergence and impact in the Western Hemisphere. Despite the presence of a sub-type of WNV (Kunjin virus, KUN) in Australia, a potential ecological niche could be occupied by an exotic strain of WNV of the North American type. This study assesses the probability an exotic strain of WNV enters Australia via an infected mosquito in an aircraft from the United States (U.S.) landing at Sydney airport, the probability it spreads to susceptible species and the impact of the resulting outbreak on human and animal health. A release, exposure and consequence assessment were conducted using expert opinion and scientific literature to parameterise the inputs for the models (OIE, 2009). Following establishment of WNV in Australia, the spatio-temporal spread of WNV was predicted over a six year period based on the Australian human and equine populations at-risk, the known distribution of other mosquito-borne flaviviruses in Australia, climatic factors, and the spread of WNV in the U.S. following it's incursion in New York City in 1999. The impact of this spread was measured as a multiplier of human and equine demographics using the U.S. incidence and case fatality rates as a reference. For an 8 month period from September to April (considering seasonal impact on mosquito activity during the coldest months in Australia and the U.S.), and assuming WNV is endemic in the U.S., the median probability an infected mosquito is introduced is 0.17, and the median number of infected mosquitoes introduced is predicted to be zero, with a 95th percentile range of one. The overall probability of a WNV outbreak (WNV released into Australia, susceptible hosts exposed and the virus spread) occurring in the human and the horse population during this time period is estimated to be 7.0×10(-6) and 3.9×10(-6), respectively. These values are largely influenced by the presence of mosquitoes in aircrafts and whether the introduced infected mosquito contacts wild birds. Results of this study suggest there is a low risk of introduction and spread of an exotic strain of WNV from the U.S via aircraft, and provides an insight into the magnitude and impact of the spread among human and horse populations. The generic framework presented could be applied to assess the potential introduction of other mosquito-borne diseases (which involve a wild bird transmission cycle) via international aircraft movements.

Preventive veterinary medicine

1873-1716

2013

10.1016/j.prevetmed.2012.09.018

Cognitive dysfunction in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric syndromes associated with systemic lupus erythematosus are common, but diverse in etiology and presentation. Cognitive dysfunction is prevalent among these syndromes, but exhibit a significant degree of heterogeneity both within and between patient variability. Earlier studies of SLE-associated cognitive dysfunction addressed its identification and description. Common associations were repeatedly acknowledged, including concomitant or past neuropsychiatric disease, use of corticosteroids, disease activity, emotional disturbance, and antiphospholipid antibodies. The past several years have focused more on elucidating the relative strengths of various risk associations, patterns of cognitive abnormalities, both cross-sectionally and longitudinally (, clinical course), and novel means to identify cognitive impairment, both functionally and biologically.

Current opinion in rheumatology

1040-8711

2002

10.1097/00002281-200209000-00005

[Hemorrhagic lesion of the corpus callosum in influenza-associated encephalitis].

We describe a rare case of Influenza B-associated encephalopathy with hemorrhagic lesions of the corpus callosum. A 12-year-old Caucasian girl presented a 24-h fever followed by partial seizure, secondarily generalized, and disturbance of consciousness. Magnetic resonance imaging on Day 2 of her illness showed two hemorrhagic lesions of the corpus callosum. The Influenza B virus was found on nasopharyngeal swab. Neurologic signs had completely recovered by Day 3. A review of the literature identified a few similar cases; the common features include a relatively older age and prompt and complete recovery from clinical symptoms. This is the first report to describe hemorrhagic lesions of the corpus callosum in influenza.

Archives de pediatrie : organe officiel de la Societe francaise de pediatrie

1769-664X

2010

10.1016/j.arcped.2010.02.010

The Impact of Adulticide on Culex Abundance and Infection Rate in North Shore of Cook County, Illinois.

Mosquito surveillance is critical to reduce the risk of West Nile virus (WNV) transmission to humans. In response to surveillance indicators such as elevated mosquito abundance or increased WNV levels, many mosquito control programs will perform truck-mounted ultra-low volume (ULV) adulticide application to reduce the number of mosquitoes and associated virus transmission. Despite the common use of truck-based ULV adulticiding as a public health measure to reduce WNV prevalence, limited evidence exists to support a role in reducing viral transmission to humans. We use a generalized additive and fused ridge regression model to quantify the location-specific impact of truck-mounted ULV adulticide spray efforts from 2010 to 2018 in the North Shore Mosquito Abatement District (NSMAD) in metropolitan Chicago, IL, on commonly assessed risk factors from NSMAD surveillance gravid traps: Culex abundance, infection rate, and vector index. Our model also takes into account environmental variables commonly associated with WNV, including temperature, precipitation, wind speed, location, and week of year. Since it is unlikely ULV adulticide spraying will have the same impact at each trap location, we use a spatially varying spray effect with a fused ridge penalty to determine how the effect varies by trap location. We found that ULV adulticide spraying has an immediate temporary reduction in abundance followed by an increase after 5 days. It is estimated that mosquito abundance increased more in sprayed areas than if left unsprayed in all but 3 trap locations. The impact on infection rate and vector index were inconclusive due to the large error associated with estimating trap-specific infection rates.

Journal of the American Mosquito Control Association

1943-6270

2022

10.2987/21-7036

West Nile virus infection in kidney and pancreas transplant recipients in the Dallas-Fort Worth Metroplex during the 2012 Texas epidemic.

In 2012, the United States experienced one of its worst West Nile virus (WNV) epidemics, reporting 5,387 human cases and final death toll of 243. Texas was at the epicenter of the outbreak, with 1,875 reported cases and 89 deaths that year. The Texas outbreak centered mainly in the Dallas-Fort Worth area where 30 deaths were reported. We report three cases of severe WNV infection complicated by meningoencephalitis in our organ transplant population.

Transplantation

1534-6080

2014

10.1097/01.TP.0000438621.81686.ab

An atypical case of febrile infection-related epilepsy syndrome following acute encephalitis: impact of physiotherapy in regaining locomotor abilities in a patient with neuroregression.

Encephalitis refers to inflammation of the brain parenchyma. It is potentially life-threatening with the highest incidence and severity in younger children. Febrile infection-related epilepsy syndrome (FIRES) is a condition, in which a child develops a nonspecific febrile illness that may not persist when the initial seizure activity begins. However, an electroencephalogram (EEG) shows that the child is in status epilepticus. We report the case of a five-year-old male who presented with difficulty to maintain sitting posture, and inability to stand and walk without support, following viral encephalitis at the age of one year. He had motor, visual, speech and cognitive impairment along with a seizure disorder. The physiotherapy interventions including neurodevelopmental treatment (NDT) and sensory integration (SI) helped in regaining locomotion ability in the child. The study aims to assess the impact of physiotherapy interventions on regaining locomotor ability in a child with FIRES following infective encephalitis.

The Pan African medical journal

1937-8688

2020

10.11604/pamj.2020.36.101.23855

Identification and Genomic Characterization of Parvovirus B19V Genotype 3 Viruses from Cases of Meningoencephalitis in West Bengal, India.

Brain infections are a major public health problem in India and other parts of the world, causing both mortality and lifelong disability. Even after a thorough investigation, many cases remain without an etiological diagnosis. Primate erythroparvovirus 1 (B19V) has been identified as a pathogen associated with undiagnosed meningoencephalitis in other settings, including the United Kingdom, France, and Latvia. Here, we reported 13/403 (3.2%) B19V PCR positive cases of meningoencephalitis in West Bengal, India. The positive samples were mostly from children (10/13, 76.92%) and presented as a spectrum consisting of acute encephalitis (7/13), acute meningoencephalitis (3/13), and meningitis (3/13). Of the 13 cases, 8/13 (61.5%) had no known etiology and 5/13 (38.5%) had a previous etiological diagnosis. The cases did not cluster in time or by location, suggesting sporadic occurrence rather than outbreaks. We were able to retrieve the complete B19V genomes from cerebrospinal fluid (CSF) in 12/13 cases. The sequences clustered into genotype 3b with complete genomes from Brazil, Ghana, and France, and partial genomes from India and Kyrgyzstan. This is the first report of B19V in cases of neurological infections from India. It highlights the need to evaluate the causal relationship between B19V with meningoencephalitis in the country. These were also the first complete genomes of genotype 3b from CSF and will be critical in the evaluation of the relationship between genotypes and disease. <b>IMPORTANCE</b> Cases of meningoencephalitis with no known etiology remain a major challenge to clinical management of brain infections across the world. In this study, we detected and characterized the whole-genome of primate erythroparvovirus 1 (B19V) in cases of meningoencephalitis in India. Our work highlighted the association between B19V and brain infections which has been reported in other countries. Our work also emphasized the need to examine the role of B19V in meningoencephalitis, specifically whether it caused or contributed to the disease together with other pathogens in India. Our study provided the first 12 genomes of B19V from cerebrospinal fluid. These genomes will contribute to an understanding of how the virus is changing across different locations and over time.

Microbiology spectrum

2165-0497

2022

10.1128/spectrum.02251-21

Roe deer sera used for TBE surveillance in Austria.

A large majority of Austrian citizens are aware of tick-borne encephalitis (TBE), consequently reflected by a high vaccination rate of 85%. In return, risk assessment and disease mapping on human cases might be hampered due to high and inhomogeneous vaccination rates and travel habitats of humans. The roe deer was used to obtain a starting point for the integral view on the actual risk of TBE in Austria. The roe deer exhibits several attributes which makes it suitable as an indicator species: the roe deer has a restricted home range and it is known to be a heavy tick carrier. Furthermore it sero-converts after infection with TBE, but no outbreak occurs. Sera from 945 roe deer were obtained from all over Austria and screened with IFAT for the antibodies against TBE. Twenty-two positive samples, 2.4%, and 17 samples at the borderline titre of 1:16 were identified. The majority of the positive samples, 70.6%, were located in known TBE areas based on human cases. Further research is needed to confirm or reject new endemic foci of TBE transmission.

Ticks and tick-borne diseases

1877-9603

2015

10.1016/j.ttbdis.2015.03.018

[Molecular epidemiology of tick-borne encephalitis].

The review presents information on the development of studies into the molecular epidemiology of tick-borne encephalitis (TBE) in Russia and foreign countries. The existence of three major virus genotypes has been established by various techniques, such as genomic fragment sequencing, molecular hybridization using genotype-specific probes, and restriction fragment length polymorphism test. Each of the genotypes prevails in different parts of a natural habitat; the Ural-Siberian genotype (a Siberian subtype) is most commonly encountered. The genetic differences between the strains belonging to different genotypes are great and comparable with differences between some mammalian flaviviruses transmitted by ticks (viruses of a TBE complex). Further studies of the molecular epidemiology of TBE are of importance in understanding the evolution of the causative agent, improving the taxonomy and the classification of flavivuruses, and designing highly effective methods for the specific diagnosis, prevention, and treatment of the disease.

Voprosy virusologii

0507-4088

2007

No DOI available

Serological evidence for West Nile virus infection in horses in Croatia.

No abstract available

The Veterinary record

0042-4900

2007

10.1136/vr.160.22.772

Inflammation and clinical presentation in neurodegenerative disease: a volatile relationship.

A proposed immune mechanism that potentially modifies or exacerbates neurodegenerative disease presentation in older adults has received considerable attention in the past decade, with recent studies demonstrating a strong link between pro-inflammatory markers and neurodegeneration. The overarching aim of the following review is to synthesize recent research that supports a possible relationship between inflammation and clinical features of neurodegenerative diseases, including risk of development, cognitive and clinical correlates, and progression of the specified diseases. Specific emphasis is placed on providing a temporal context for the association between inflammation and neurodegeneration.

Neurocase

1465-3656

2013

10.1080/13554794.2011.654227

Suspected Methadone Toxicity: from Hospital to Autopsy Bed.

High mortality rates have been reported for methadone in both adults and children. We aimed to determine the pattern of toxicity, possible underlying diseases and treatment challenges in patients referred to our centre with early diagnosis of methadone toxicity and who later died. Medical files of all methadone-poisoned patients who had been admitted to a referral centre of toxicology between March 2011 and March 2016, died during the hospital stay and sent for autopsy to Legal Medicine Organization were retrospectively evaluated. In a total of 94 patients, autopsy findings and laboratory evaluations showed that cause of death was pure methadone toxicity in 57 (60.6%). Other causes of death were ischaemic heart disease in ten, co-ingestions (toxicities including methadone) in eight, brain haemorrhage, multi-organ failure and pneumosepsis (each in four), meningitis/encephalitis in three and head trauma and other toxicities (other than methadone but including an opioid, each in two) patients. Time of cardiopulmonary arrest was significantly different between those with pure methadone toxicity and those who died due to other causes (p = 0.01). Patients who had died due to co-ingestions and other toxicities were younger (p = 0.029) and took more bolus doses of naloxone (p = 0.042). In methadone users, especially in older ages and those with trivial response to naloxone administration, loss of consciousness should not be strictly attributed to methadone toxicity. In such patients, thorough evaluation for other possible causes of loss of consciousness is mandatory.

Basic & clinical pharmacology & toxicology

1742-7843

2017

10.1111/bcpt.12831

D2: major subgenotype of hepatitis B virus in Russia and the Baltic region.

Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.

The Journal of general virology

0022-1317

2008

10.1099/vir.0.83660-0

Longitudinal measurement of cerebrospinal fluid neurofilament light in anti-N-methyl-D-aspartate receptor encephalitis.

Biomarkers reflecting the course of patients suffering from anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) are urgently needed. Neurofilament light chains (NfL) have been studied as potential markers for neuroaxonal injury mainly in neuroinflammatory diseases, but so far there have been only in a few small reports on anti-NMDARE. We aimed to compare the longitudinal course of cerebrospinal fluid (CSF)-NfL levels and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies with clinical parameters in six patients with anti-NMDARE.

European journal of neurology

1468-1331

2021

10.1111/ene.14631

Asian travel: from the rare to the difficult.

No abstract available

Journal of travel medicine

1708-8305

2018

10.1093/jtm/tay015

Human parechovirus-3 infection: emerging pathogen in neonatal sepsis.

Human parechovirus-3 (HPeV-3) is an emerging pathogen that has been described as a cause of neonatal sepsis. Human parechoviruses are a family of viruses closely related to enteroviruses; however, enteroviral PCR will not detect HPeVs. We present clinical details of neonatal meningoencephalitis and hepatitis-coagulopathy syndrome caused by HPeV-3 infection.

The Pediatric infectious disease journal

0891-3668

2009

10.1097/INF.0b013e318194596a

Lowering Synaptogyrin-3 expression rescues Tau-induced memory defects and synaptic loss in the presence of microglial activation.

Tau is a major driver of neurodegeneration and is implicated in over 20 diseases. Tauopathies are characterized by synaptic loss and neuroinflammation, but it is unclear if these pathological events are causally linked. Tau binds to Synaptogyrin-3 on synaptic vesicles. Here, we interfered with this function to determine the role of pathogenic Tau at pre-synaptic terminals. We show that heterozygous knockout of synaptogyrin-3 is benign in mice but strongly rescues mutant Tau-induced defects in long-term synaptic plasticity and working memory. It also significantly rescues the pre- and post-synaptic loss caused by mutant Tau. However, Tau-induced neuroinflammation remains clearly upregulated when we remove the expression of one allele of synaptogyrin-3. Hence neuroinflammation is not sufficient to cause synaptic loss, and these processes are separately induced in response to mutant Tau. In addition, the pre-synaptic defects caused by mutant Tau are enough to drive defects in cognitive tasks.

Neuron

1097-4199

2021

10.1016/j.neuron.2020.12.016

Coordinated regulation and widespread cellular expression of interferon-stimulated genes (ISG) ISG-49, ISG-54, and ISG-56 in the central nervous system after infection with distinct viruses.

The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.

Journal of virology

0022-538X

2007

10.1128/JVI.01167-06

Expression of the mannose receptor CD206 in HIV and SIV encephalitis: a phenotypic switch of brain perivascular macrophages with virus infection.

We examined the expression of the mannose receptor CD206 by perivascular macrophages (PVM) in normal human and monkey brains and in brains of HIV-infected humans and of monkeys infected with simian immunodeficiency virus (SIV). Depletion of brain PVM in SIV-infected monkeys by intrathecal injection of liposome-encapsulated bisphosphonates eliminated CD206-expressing cells in the brain, confirming their perivascular location and phagocytic capacity. In vivo labeling with bromodeoxyuridine in normal uninfected and SIV-infected macaques in combination with CD206 immunostaining revealed a CD206+-to-CD206- shift within pre-existing PVM during SIV brain infection and neuroinflammation. These findings identify CD206 as a unique marker of human and macaque PVM, and underscore the utility of this marker in studying the origin, turnover and functions of these cells in AIDS.

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

1557-1904

2014

10.1007/s11481-014-9564-y

Fatal human rabies caused by European bat Lyssavirus type 2a infection in Scotland.

We wish to report the first recorded case of indigenous human rabies caused by a bat bite in the United Kingdom in 100 years. This instructive case report highlights a number of key lessons: first, bites from insectivorous bats indiginous to the United Kingdom can cause rabies in humans; second, rabies immunization is essential for bat-handlers, and postexposure treatment for rabies is essential for patients bitten by bats; third, patients able to give a history who present with acute flaccid paralysis and/or presumptive viral encephalitis should be asked if they have been bitten by bats, irrespective of travel history, or this history should be obtained from family or friends; fourth, antemortem diagnosis of bat rabies (EBLV type 2a infection) in humans is possible using RT-PCR.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

1537-6591

2003

10.1086/376641

Unsuccessful cyclosporine plus prednisolone therapy for autoimmune meningoencephalitis in three dogs.

A 4-year-old female Maltese (case 1), a 9-year-old castrated male shih tzu (case 2) and 2-year-old female Pomeranian (case 3) presented with neurological signs, such as head tilt, ataxia, circling and paresis. The three cases were tentatively diagnosed as having meningoencephalitis of unknown etiology based on computed tomography scan and cerebrospinal fluid analysis. All patients were managed with cyclosporine plus prednisolone therapy. The survival times of the three patients were 170, 70 and 21 days, respectively. After the cases died, we performed necropsy and histopathological examination for definitive diagnosis. Based on the necropsy, histopathological and immunohistochemical examinations, cases 1, 2 and 3 were definitely diagnosed as having necrotizing meningoencephalitis, necrotizing leukoencephalitis and granulomatous meningoencephalitis, respectively. This case report demonstrated the clinical findings, brain CT characteristics and histopathological and immunohistochemical features of NME, NLE and GME in dogs and discussed the reason for the relatively short survival times under cyclosporine plus prednisolone therapy.

The Journal of veterinary medical science

1347-7439

2013

10.1292/jvms.12-0503

Dancing eyes dancing feet syndrome-a report of two cases.

Opsoclonus Myoclonus (OMS) is a rare neurological disorder which appears to be the result of an autoimmune dysfunction. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people every year. It affects 2 to 3% of children. Opsoclonus Myoclonus, which manifests itself as post infectious encephalopathy, occasionally along with HIV infection, post Streptococcal infection, West Nile virus encephalitis and Rickettsial infection, most often presents as a paraneoplastic syndrome, which is especially caused by occult neuroblastoma which is commonly seen in childhood and occurs in adults in relation to breast cancer and small cell lung cancer. In this study, two adult post infectious cases which had rare manifestations, have been presented. The cases were managed by using corticosteroids.

Journal of clinical and diagnostic research : JCDR

2249-782X

2014

10.7860/JCDR/2014/7184.4339

Lidocaine treatment in refractory status epilepticus resulting from febrile infection-related epilepsy syndrome: a case report and follow-up.

We report the management of refractory status epilepticus (SE) by using continuous intravenous infusions of lidocaine in a previously healthy 15-year-old girl with a "catastrophic encephalopathy" in whom a diagnosis of febrile infection-related epilepsy syndrome was supposed. One week after a banal pharyngitis and fever, the patient presented confusion and intractable clusters of seizures. Although she underwent multiple examinations investigating all possible etiologies (intracranial infection, autoimmune disease, or toxic and metabolic illness), all results were negative except a feeble positivity to Mycoplasma pneumoniae serum antibodies. SE was initially treated with benzodiazepine followed by administration of barbiturates and subsequent induction of coma because of refractory SE; different antiepileptic drugs (AEDs) were given at different times in a period of 6 weeks but clinical and electroencephalographic improvements were achieved only after continuous infusion of lidocaine. When she recovered from SE, the patient developed severe psychomotor and cognitive impairment associated with cerebral atrophy. Treatment with lidocaine or other alternative drugs in cases of prolonged SE should be taken into account as soon as it becomes clear that the clinical condition is refractory to common AEDs included in available guidelines for SE treatment, to improve the bad outcome of this severe condition, at least limiting the negative effects of prolonged high metabolic demand due to continuous epileptiform activity and/or the possible negative effects of prolonged burst-suppression coma.

Neuropediatrics

1439-1899

2015

10.1055/s-0034-1389898

The impact of climatic conditions on the dynamics of tick-borne encephalitis in Slovakia in 2012-2016.

The main aim of our work was to analyse the development of the dynamics of tick-borne encephalitis (TBE) in connection with climatic conditions in Slovakia in 2012-2016.

Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne

1210-7913

2023

No DOI available

Serum S100B levels in patients with cerebral and extracerebral infectious disease.

S100B has been shown to increase in cerebrospinal fluid (CSF) and serum after various neurological diseases and it has been postulated that S100B could serve as a serum marker for brain damage. However there is limited information concerning serum S100B levels in infectious diseases of the brain. Blood samples were collected from patients at the Department of Infectious Diseases at or soon after admission. The different diagnoses studied were bacterial meningitis, pneumonia, viral meningitis, cerebral abscess, enteritis, erysipelas, viral encephalitis and neuroborreliosis. A serum S100B level > 0.15 microg/l was defined as increased. 57 patients were included in the study. S100B was elevated in 33% of patients (19/57). 73% (8/11) of patients with bacterial meningitis showed increased levels compared to 7% (1/14) of patients with viral meningitis. Viral encephalitis showed the highest mean S100B levels (mean 0.58 microg/l). 25% (6/24) of patients with extracerebral infections showed raised S100B levels. S100B levels were generally higher in patients with cerebral infections than in extracerebral infections. However, both false negative and false positive S100B levels were observed which may limit the use of S100B as a brain specific serum marker.

Scandinavian journal of infectious diseases

0036-5548

2004

10.1080/00365540310017294

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis.

The HLA genes, as well as the innate immune KIR genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis.

Oncotarget

1949-2553

2018

10.18632/oncotarget.24778

A chimeric alphavirus replicon particle vaccine expressing the hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques from measles.

Measles remains a major cause of child mortality, in part due to an inability to vaccinate young infants with the current live attenuated virus vaccine (LAV). To explore new approaches to infant vaccination, chimeric Venezuelan equine encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the hemagglutinin (H) and fusion (F) proteins of measles virus (MV). Juvenile rhesus macaques vaccinated intradermally with a single dose of VEE/SIN expressing H or H and F proteins (VEE/SIN-H or VEE/SIN-H+F, respectively) developed high titers of MV-specific neutralizing antibody and gamma-interferon (IFN-gamma)-producing T cells. Infant macaques vaccinated with two doses of VEE/SIN-H+F also developed neutralizing antibody and IFN-gamma-producing T cells. Control animals were vaccinated with LAV or with a formalin-inactivated measles vaccine (FIMV). Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not. Antibody was boosted by challenge in all groups. T-cell responses to challenge were biphasic, with peaks at 7 to 25 days and at 90 to 110 days in all groups, except for the LAV group. Recrudescent T-cell activity coincided with the presence of MV RNA in peripheral blood mononuclear cells. We conclude that VEE/SIN expressing H or H and F induces durable immune responses that protect from measles and offers a promising new approach for measles vaccination. The viral and immunological factors associated with long-term control of MV replication require further investigation.

Journal of virology

1098-5514

2010

10.1128/JVI.01566-09

[Herpes simplex encephalitis without cerebrospinal fluid pleocytosis in a patient with bullous pemphigoid: a case report].

A 78-year-old woman was diagnosed with bullous pemphigoid 2 months ago, and she had been treated with steroid and plasmapheresis. She developed sudden fever, vomiting, disorientation, and abnormal behavior. Diffusion weighted images and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the right temporal lobe hippocampus and right insular cortex. Cerebrospinal fluid (CSF) examination showed normal cell count (4/mm(3)), but was positive for HSV1-DNA by PCR. She was diagnosed with herpes simplex encephalitis (HSE), and acyclovir was started on the first day of admission. She had complete recovery, and was discharged. She didn't show CSF pleocytosis throughout her course of HSE. No CSF pleocytosis could be due probably to her immunosuppressed state under the steroid therapy for bullous pemphigoid. Because the morbidity and mortality of HSE is drastically reduced by early antiviral treatment, it is important to accelerate the diagnosis and treatment of HSE, especially in immunosuppressed or immunocompromised hosts.

Rinsho shinkeigaku = Clinical neurology

1882-0654

2016

10.5692/clinicalneurol.cn-000870

Interstitial granulomatous dermatitis and concurrent immunotherapy associated encephalitis with nivolumab and ipilimumab.

Immune-related adverse events (irAEs) are common in patients receiving immune checkpoint inhibitors for metastatic melanoma and other advanced malignancies. Cutaneous, gastrointestinal, and endocrine (thyroid) irAEs are most prevalent, whereas neurologic irAEs are rare. We present a 73-year-old man with dementia and metastatic melanoma who developed immunotherapy-associated encephalitis and subsequently, interstitial granulomatous dermatitis with nivolumab/ipilimumab. High-dose corticosteroids successfully treated both conditions, though he never regained his baseline mental status. We review the literature on interstitial granulomatous dermatitis and encephalitis with immunotherapy.

Dermatology online journal

1087-2108

2022

10.5070/D328257399

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19.

Revue neurologique

0035-3787

2021

10.1016/j.neurol.2021.01.004

Hypoxic induction of caspase-11/caspase-1/interleukin-1beta in brain microglia.

Caspase-11 is an inducible protease that plays an important role in both inflammation and apoptosis. Inflammatory stimuli induce and activate caspase-11, which is required for the activation of caspase-1 or interleukin-1beta (IL-1beta) converting enzyme (ICE). Caspase-1 in turn mediates the maturation of proinflammatory cytokines such as IL-1beta, which is one of the crucial mediators of neurodegeneration in the central nervous system. Here, we report that hypoxic exposure of cultured brain microglia (BV-2 mouse microglia cells and rat primary microglial cultures) induces expression and activation of caspase-11, which is accompanied by activation of caspase-1 and secretion of mature IL-1beta and IL-18. Hypoxic induction of caspase-11 was observed in both mRNA and protein levels, and was mediated through p38 mitogen-activated protein kinase pathway. Transient global ischemia in rats also induced caspase-11 expression and IL-1beta production in hippocampus supporting our in vitro findings. Caspase-11-expressing cells in hippocampus were morphologically identified as microglia. Taken together, our results indicate that hypoxia induces a sequential event-caspase-11 induction, caspase-1 activation, and IL-1beta release-in brain microglia, and point out the importance of initial caspase-11 induction in hypoxia-induced inflammatory activation of microglia.

Brain research. Molecular brain research

0169-328X

2003

10.1016/s0169-328x(03)00135-9

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis: A case report.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presents with the features of herpes simplex encephalitis (HSE), which is rare and has been described in only a few case reports. Our case describes a 17-year-old female with no significant previous medical history presenting with an acute onset of fever, headache, and epilepsy, similar to HSE. Computed tomography of the brain showed bilateral basal ganglia calcification. Magnetic resonance imaging demonstrated gyriform restricted diffusion with T2-weighted images prolongation. Further investigation showed elevated blood lactate concentration at rest. Hence, MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. The clinical presentation and imaging studies of MELAS are variable and may mimic those of HSE. Infection may have also precipitated MELAS manifestation in this patient. Laboratory features, such as elevated lactate, basal ganglia calcification, and gyriform restricted diffusion may be helpful in identifying patients with MELAS.

Radiology case reports

1930-0433

2022

10.1016/j.radcr.2022.04.019

Paraneoplastic limbic encephalitis associated with mixed olfactory neuroblastoma and craniopharyngioma: A case report and literature review.

Paraneoplastic limbic encephalitis (PLE) is a rare disorder of the nervous system associated with malignant disease. It has a subacute onset with the following symptoms: cognitive dysfunction, seizures, irritability, hallucinations, and short-term memory loss. Herein, we report the case of a 35-year-old man with PLE, an olfactory neuroblastoma (ONB) admixed with craniopharyngioma, and serum anti-Hu antibodies.

Medicine

1536-5964

2018

10.1097/MD.0000000000010932

Influenza and Other Prophylactic Vaccination Coverage in Polish Adult Patients Undergoing Allergen Immunotherapy-A Survey Study among Patients and Physicians.

Vaccines against infectious diseases may raise safety concerns in patients undergoing allergen immunotherapy (AIT). The objective of our study was to investigate influenza vaccine and other selected prophylactic vaccines coverage in patients treated with AIT and the attitude of physicians towards vaccinations in this group of patients. We conducted a questionnaire-based study among patients undergoing AIT and physicians. The patients’ survey evaluated influenza and other prophylactic vaccines coverage. The physicians’ survey assessed their experience and opinions on prophylactic vaccinations during AIT. In total, 176 patients (aged 18−79 years) and 120 doctors filled the questionnaires. Patients were assigned to two groups—inhaled allergens group (n = 101) and insect venoms group (n = 68). The number of patients who received any dose (36% and 45%, p = 0.26), as well as two or more doses (17% and 22%, p = 0.43) of influenza vaccine was comparable between two groups. However, in both groups there was a significant (p < 0.0001) decrease in influenza vaccine uptake after the beginning of AIT. Patients from the inhaled allergens group declared a higher tetanus vaccine rate (41% vs. 19%, p = 0.004). The groups did not differ in the pneumococcal and tick-borne encephalitis vaccination coverage. A majority of doctors believe that prophylactic vaccinations in patients undergoing AIT are safe and effective (96% and 94%, respectively); however, as many as 87% of them identify with the need to create clear recommendations regarding vaccinating patients undergoing AIT. Prophylactic vaccine coverage is not satisfactory among Polish adult patients undergoing AIT. Polish doctors are convinced of the validity of prophylactic vaccinations during AIT.

Vaccines

2076-393X

2022

10.3390/vaccines10040576

Clinical manifestations, diagnostic criteria and therapy of Hashimoto's encephalopathy: report of two cases.

Hashimoto's encephalopathy (HE) is a rare, still not well understood, autoimmune disease with neurological and psychiatric manifestations. and elevated titers of antithyroid antibodies in serum and cerebrospinal fluid (CSF) as a hallmark of the disease. Patients are mostly women. Current diagnostic criteria include corticosteroide responsiveness, but it is the case in only 50% of patients with HE. In steroid non-responders other immunomodulatory therapies or plasmapheresis could be applied. Disease course can be acute, subacute, chronic or relapsing-remitting. Two distinct forms emerged from the reported cases: a vasculitic type characterized by multiple relapsing-remitting stroke-like episodes and mild cognitive impairment and a diffuse progressive type characterized by dementia and psychiatric symptoms. Both forms may be accompanied by depressed level of consciousness (stupor or coma), tremor, seizures, or myoclonus. We present two patients with two distinct forms of HE who had different clinical manifestations and response to therapy.

Journal of the neurological sciences

1878-5883

2010

10.1016/j.jns.2009.09.030

Four-segmented Rift Valley fever virus-based vaccines can be applied safely in ewes during pregnancy.

Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. This mosquito-borne virus, belonging to the genus Phlebovirus of the family Bunyaviridae contains a tri-segmented negative-strand RNA genome. Previously, we developed four-segmented RVFV (RVFV-4s) variants by splitting the M-genome segment into two M-type segments each encoding one of the structural glycoproteins; Gn or Gc. Vaccination/challenge experiments with mice and lambs subsequently showed that RVFV-4s induces protective immunity against wild-type virus infection after a single administration. To demonstrate the unprecedented safety of RVFV-4s, we here report that the virus does not cause encephalitis after intranasal inoculation of mice. A study with pregnant ewes subsequently revealed that RVFV-4s does not cause viremia and does not cross the ovine placental barrier, as evidenced by the absence of teratogenic effects and virus in the blood and organs of the fetuses. Altogether, these results show that the RVFV-4s vaccine virus can be applied safely in pregnant ewes.

Vaccine

1873-2518

2017

10.1016/j.vaccine.2017.04.024

Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer.

Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). Here we report results from the open-label, dose-escalation, Phase 1b ECHO-110 study evaluating epacadostat plus atezolizumab in patients with previously treated Stage IIIB/IV nonsmall cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum-based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment. Oral epacadostat (25, 50, 75, 100, 200 or 300 mg) was administered twice daily (BID) with intravenous atezolizumab 1,200 mg every 3 weeks (Q3W). Primary endpoints were safety, tolerability and dose-limiting toxicities (DLTs). Twenty-nine patients received ≥1 dose of treatment. The maximum tolerated dose of epacadostat was not reached. Two patients had DLTs: one patient with Grade 3 dehydration and hypotension (epacadostat 200 mg BID); one patient with Grade 3 hyponatremia and Grade 4 autoimmune encephalitis (epacadostat 300 mg BID). Twenty-three patients (79%) had treatment-related adverse events (AEs); seven patients (24%) experienced Grade 3/4 events; five patients (17%) discontinued treatment due to treatment-related AEs. No fatal treatment-related AEs occurred. One patient achieved a partial response (objective response rate, 3%), which was maintained for 8.3 months; eight patients had stable disease. Baseline tumoral programmed cell death ligand 1 (PD-L1) and IDO expression were low among patients with evaluable samples (1 of 23 expressed PD-L1; 5 of 17 expressed IDO). Epacadostat pharmacokinetics was comparable to historical controls. Epacadostat, at doses up to 300 mg BID, combined with atezolizumab 1,200 mg Q3W was well tolerated in patients with previously treated NSCLC, although clinical activity was limited.

International journal of cancer

1097-0215

2020

10.1002/ijc.32951

A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.

The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS.

BMC neuroscience

1471-2202

2004

10.1186/1471-2202-5-10

A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge.

Currently there are no licensed antiviral treatments for the Alphaviruses Venezuelan equine encephalitis virus (VEEV), Everglades virus and Mucambo virus. We previously developed a humanised version of the mouse monoclonal antibody 1A3B-7 (Hu1A3B-7) which exhibited a wide range of reactivity in vitro and was able to protect mice from infection with VEEV. Continued work with the humanised antibody has now demonstrated that it has the potential to be a new human therapeutic. Hu1A3B-7 successfully protected mice from infection with multiple Alphaviruses. The effectiveness of the humanisation process was determined by assessing proliferation responses in human T-cells to peptides derived from the murine and humanised versions of the V(H) and V(L) domains. This analysis showed that the number of human T-cell epitopes within the humanised antibody had been substantially reduced, indicating that Hu1A3B-7 may have reduced immunogenicity in vivo.

Virology

1096-0341

2012

10.1016/j.virol.2012.01.038

Autoimmune Epilepsy in Children: Unraveling the Mystery.

Although many neurologists are familiar with the clinical presentations of anti-N-methyl-d-aspartate receptor or limbic encephalitides, there remains much mystery surrounding autoimmune etiologies of subacute and chronic epilepsies. In addition, the subtleties and differences in presentation in the pediatric population limit diagnosis and challenge clinicians. In the absence of an acute encephalitic picture, it is likely that many clinicians do not test for autoimmune disorders due to the uncertainty surrounding the selection of appropriate candidates for testing and immunomodulation. Recent developments have expanded the definition of epilepsy related to autoimmune mechanisms. Based on current knowledge, autoimmune epilepsy can best be thought of as a subset of autoimmune encephalitis where seizures and epilepsy are the primary presenting factor. Autoimmune epilepsy has been increasingly recognized as a contributor to drug-resistant epilepsies; however, identification of affected individuals remains challenging, particularly in the pediatric population. Our understanding of autoimmune epilepsy continues to evolve as more individuals with epilepsy are tested for antibodies to neuronal proteins and as additional antibodies are being identified. This article provides an overview of the clinical features most commonly associated with positive antibody testing in epilepsy and the scales that are currently available to screen patients for antibody testing and response to immunotherapy. Literature-based recommendations are presented for the modification and validation of current scales to increase applicability to children.

Pediatric neurology

1873-5150

2020

10.1016/j.pediatrneurol.2020.03.016

Rodent Models of Congenital Cytomegalovirus Infection.

Human cytomegalovirus (HCMV) is a leading viral cause of congenital infections in the central nervous system (CNS) and may result in severe long-term sequelae. High rates of sequelae following congenital HCMV infection and insufficient antiviral therapy in the perinatal period makes the development of an HCMV-specific vaccine a high priority of modern medicine. Due to the species specificity of HCMV, animal models are frequently used to study CMV pathogenesis. Studies of murine cytomegalovirus (MCMV) infections of adult mice have played a significant role as a model of CMV biology and pathogenesis, while MCMV infection of newborn mice has been successfully used as a model of perinatal CMV infection. Newborn mice infected with MCMV have high levels of viremia during which the virus establishes a productive infection in most organs, coupled with a robust inflammatory response. Productive infection in the brain parenchyma during early postnatal period leads to an extensive nonnecrotizing multifocal widespread encephalitis characterized by infiltration of components of both innate and adaptive immunity. As a result, impairment in postnatal development of mouse cerebellum leads to long-term motor and sensor disabilities. This chapter summarizes current findings of rodent models of perinatal CMV infection and describes methods for analysis of perinatal MCMV infection in newborn mice.

Methods in molecular biology (Clifton, N.J.)

1940-6029

2021

10.1007/978-1-0716-1111-1_18

Identification of gene regions regulating inflammatory microglial response in the rat CNS after nerve injury.

Local CNS inflammation takes place in many neurological disorders and is important for autoimmune neuroinflammation. Microglial activation is strain-dependent in rats and differential MHC class II expression is influenced by variations in the Mhc2ta gene. Despite sharing Mhc2ta and MHC class II alleles, BN and LEW.1N rats differ in MHC class II expression after ventral root avulsion (VRA). We studied MHC class II expression and glial activation markers in BN rats after VRA. Our results demonstrate that MHC class II expression originates from a subpopulation of IBA1(+), ED1(-), and ED2(-) microglia. We subsequently performed a genome-wide linkage scan in an F2(BNxLEW.1N) population, to investigate gene regions regulating this inflammatory response. Alongside MHC class II, we studied the expression of MHC class I, co-stimulatory molecules, complement components, microglial markers and Il1b. MHC class II and other transcripts were commonly regulated by gene regions on chromosomes 1 and 7. Furthermore, a common region on chromosome 10 regulated expression of complement and co-stimulatory molecules, while a region on chromosome 11 regulated MHC class I. We also detected epistatic interactions in the regulation of the inflammatory process. These results reveal the complex regulation of CNS inflammation by several gene regions, which may have relevance for disease.

Journal of neuroimmunology

1872-8421

2009

10.1016/j.jneuroim.2009.05.004

Temporal lobe epilepsy: analysis of failures and the role of reoperation.

To analyze failures and reoperations in temporal lobe epilepsy (TLE), and compare these patients with those seizure-free, and to determine any significant differences between the groups.

Acta neurologica Scandinavica

0001-6314

2005

10.1111/j.1600-0404.2005.00371.x

Beneficial and detrimental functions of microglia during viral encephalitis.

Microglia are resident immune cells of the central nervous system (CNS) with multiple functions in health and disease. Their response during encephalitis depends on whether inflammation is triggered in a sterile or infectious manner, and in the latter case on the type of the infecting pathogen. Even though recent technological innovations advanced the understanding of the broad spectrum of microglia responses during viral encephalitis (VE), it is not entirely clear which microglia gene expression profiles are associated with antiviral and detrimental activities. Here, we review novel approaches to study microglia and the latest concepts of their function in VE. Improved understanding of microglial functions will be essential for the development of new therapeutic interventions for VE.

Trends in neurosciences

1878-108X

2022

10.1016/j.tins.2021.11.004

Innate resistance to flavivirus infection in mice controlled by Flv is nitric oxide-independent.

Innate resistance to flaviviruses in mice is active in the brain where it restricts virus replication. This resistance is controlled by a single genetic locus, FLV, located on mouse chromosome 5 near the locus encoding the neuronal form of nitric oxide synthase (Nos1). Since nitric oxide (NO) has been implicated in antiviral activity, its involvement in natural resistance to flaviviruses has been hypothesized. Here we present data on NO production before and during flavivirus infection in both brain tissue and peritoneal macrophages from two flavivirus-resistant (FLV(r)) and one congenic susceptible (FLV(s)) mouse strains. This study provides evidence that NO is not involved in the expression of flavivirus resistance controlled by FLV since: (a) there is no difference in brain tissue NO levels between susceptible and resistant mice, and (b) lipopolysaccharide-induced NO does not abrogate the difference in flavivirus replication in peritoneal macrophages from susceptible and resistant mice.

The Journal of general virology

0022-1317

2001

10.1099/0022-1317-82-3-603

Plasmid DNA encoding CCR7 ligands compensate for dysfunctional CD8+ T cell responses by effects on dendritic cells.

Lymphotoxin alpha-deficient (LTalpha-/-) mice, which lack lymph nodes and possess a disorganized spleen, develop dysfunctional CD8+ T cells upon HSV infection and readily succumb to herpes encephalitis. Such mice do develop apparently normal peptide-specific CD8+ T cell responses, as measured by MHC class I tetramer staining, but the majority of cells fail to become cytotoxic or express peptide-induced IFN-gamma production. In the present study, we demonstrate that functional defects of CD8+ T cells in LTalpha-/- mice can be largely rectified by the administration of plasmid DNA encoding CCR7 ligands before HSV infection. Treated mutant mice developed increased peptide-specific cytotoxic responses, enhanced numbers of CD8+ T cells capable of producing IFN-gamma, as well as improved resistance to HSV challenge. The corrective effect of chemokine treatment appeared to result from improved dendritic cell-mediated Ag presentation. Thus, a major consequence of the treatment was an increase in splenic dendritic cell number in CCR7 ligand-treated LTalpha-/- mice with such splenocyte populations showing improved APC activity in vitro. Our results document that functional defects of CD8+ T cells can be corrected, and indicate the value of plasmid vector encoding appropriate chemokines to achieve such immunotherapy.

Journal of immunology (Baltimore, Md. : 1950)

0022-1767

2001

10.4049/jimmunol.167.7.3592

CSF tau microtubule-binding region identifies pathological changes in primary tauopathies.

Despite recent advances in fluid biomarker research in Alzheimer's disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau₂₇₅ and MTBR-tau₂₈₂) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPT and AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPT and AD compared to control and other FTLD-tau (for example, Pick's disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau₂₇₅ and MTBR-tau₂₈₂ may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs.

Nature medicine

1546-170X

2022

10.1038/s41591-022-02075-9

Time-course of the expression of inflammatory cytokines and matrix metalloproteinases in the striatum and mesencephalon of mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a dopaminergic neurotoxin.

Injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice results in a retrograde nigrostriatal dopaminergic pathway denervation and subsequent tissue reorganization. Since the role of inflammatory mediators after MPTP remains unclear, proinflammatory cytokine and matrix metalloproteinase (MMP) expression were evaluated by comparative RT-PCR during denervation and tissue reorganization following a single-dose of MPTP (40 mg/kg, s.c.) in young (8-week-old) mice. The time-course of denervation/reorganization was assessed through [(3)H]GBR-12935 binding on dopamine transporter and tyrosine hydroxylase immunohistochemistry. In the striatum, TNF-alpha, IL-1alpha, IL-1beta, IL-6 and MMP-9 mRNA expression peaked on day 1. In the ventral mesencephalon, cytokines (TNF-alpha, IL-1alpha, IL-1beta) and MMP-9 mRNA expression peaked on day 3. During tissue reorganization (day 6 through 16), the only change observed in the striatum consisted of IL-1alpha mRNA and protein overexpression together with MMP-2 downregulation. Whereas the early expression of proinflammatory cytokines and MMP might participate in the retrograde nigrostriatal denervation, the late component of IL-1alpha expression suggests a possible role for this cytokine in the subsequent striatal reorganization.

Neuroscience letters

0304-3940

2003

10.1016/s0304-3940(03)00832-2

Detection and Analysis of West Nile Virus Structural Protein Genes in Animal or Bird Samples.

West Nile virus (WNV) is an important zoonotic pathogen, which is detected mainly by identification of its RNA using PCR. Genetic differentiation between WNV lineages is usually performed by complete genome sequencing, which is not available in many research and diagnostic laboratories. In this chapter, we describe a protocol for detection and analysis of WNV samples by sequencing the entire region of their structural genes capsid (C), preM/membrane, and envelope. The primary step is the detection of WNV RNA by quantitative PCR of the NS2A gene or the C gene regions. Next, the entire region containing the structural protein genes is amplified by PCR. The primary PCR product is then amplified again in parallel reactions, and these secondary PCR products are sequenced. Finally, bioinformatic analysis enables detection of mutations and classification of the samples of interest. This protocol is designed to be used by any laboratory equipped for endpoint and quantitative PCR. The sequencing can be performed either in-house or outsourced to a third-party service provider. This protocol may therefore be useful for rapid and affordable classification of WNV samples, obviating the need for complete genome sequencing.

Methods in molecular biology (Clifton, N.J.)

1940-6029

2023

10.1007/978-1-0716-2760-0_13

The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production.

A chief Ca(2+) entry pathway in immune cells is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+) from the endoplasmic reticulum (ER). However, its physiological role in B cells remains elusive. Here, we show that ER calcium sensors STIM1- and STIM2-induced SOC influx is critical for B cell regulatory function. B cell-specific deletion of STIM1 and STIM2 in mice caused a profound defect in B cell receptor (BCR)-induced SOC influx and proliferation. However, B cell development and antibody responses were unaffected. Remarkably, B cells lacking both STIM proteins failed to produce the anti-inflammatory cytokine IL-10 because of defective activation of nuclear factor of activated T cells (NFAT) after BCR stimulation. This resulted in exacerbation of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our data establish STIM-dependent SOC influx as a key signal for B cell regulatory function required to limit autoimmunity.

Immunity

1097-4180

2011

10.1016/j.immuni.2011.03.016

[The anti-IgLON5 syndrome in clinical neurology-Report of two cases].

No abstract available

Der Nervenarzt

1433-0407

2022

10.1007/s00115-022-01344-9

Mild hypothermia inhibits nuclear factor-kappaB translocation in experimental stroke.

Nuclear factor-kappaB (NFkappaB) is a transcription factor that is activated after cerebral ischemia. NFkappaB activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. The authors previously showed that mild hypothermia is protective even when cooling begins 2 h after stroke onset. In the present study, they examined the influence of hypothermia on NFkappaB activation. Rats underwent 2 h of transient middle cerebral artery occlusion. Brains were cooled to 33 degrees C immediately after or 2 h after occlusion, and maintained for 2 h. After normothermic ischemia (brain temperature at 38 degrees C), NFkappaB cytoplasmic expression, nuclear translocation, and binding activity were observed as early as 2 h in the ischemic hemisphere and persisted at 24 h. Hypothermia decreased NFkappaB translocation and binding activity but did not alter overall expression. Hypothermia also affected the levels of NFkappaB regulatory proteins by suppressing phosphorylation of NFkappaB's inhibitory protein (IkappaB-alpha) and IkappaB kinase (IKK-gamma) and decreasing IKK activity, but did not alter overall IKK levels. Hypothermia suppressed the expression of two NFkappaB target genes: inducible nitric oxide synthase and TNF-alpha. These data suggest that the protective effect of hypothermia on cerebral injury is, in part, related to NFkappaB inhibition due to decreased activity of IKK.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

0271-678X

2003

10.1097/01.WCB.0000059566.39780.8D

Multiple demyelinating sensory and motor mononeuropathy associated with COVID-19: a case report.

The involvement of the nervous system may occur in 36.4% of patients with COVID-19. Cases have been described of cerebrovascular diseases, encephalitis, encephalopathies, and changes in smell and taste. Two months after being discharged from hospital with COVID-19, a 63-year-old male patient presented with a predominantly demyelinating multiple sensory and motor mononeuropathy. A diagnostic possibility of multiple sensory and motor demyelinating mononeuropathy (Lewis-Sumner syndrome) was made. Treatment with human immunoglobulin was initiated. COVID-19 may be associated with multiple demyelinating sensory and motor mononeuropathy.

Journal of neurovirology

1538-2443

2021

10.1007/s13365-021-01024-5

[Infectious encephalitis].

Infectious encephalitis is a severe disease of the central nervous system with high case fatality ratio and long-term sequels. Although a high proportion remains unexplained, the most frequently identified cause in all countries was always herpes simplex virus type 1. The generalisation of acyclovir dramatically improved the survival rate of herpes simplex encephalitis patients. However, a high proportion of patients still experience neuropsychological sequels. Bacteria are a usual cause of encephalitis in France. Mycobaterium tuberculosis and Listeria monocytogenes in particular should be considered in the early treatment of encephalitis patients at the time of admission. Auto-antibodies encephalitis and ADEM, although not infectious diseases, can mimick viral encephalitis and should be included in the differential diagnosis of encephalitis patients.

La Revue du praticien

0035-2640

2011

No DOI available

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

Brain : a journal of neurology

1460-2156

2018

10.1093/brain/awy151

In vitro propagation of rabies virus in mouse dorsal root ganglia cells.

Rabies virus (RV) is highly neurotropic and migrates to the neuronal soma by retrograde axonal transport from nerve terminals, after which it is taken by anterograde axonal transport to be finally released into the central nervous system (CNS) from which it disseminates, resulting in lethal encephalitis. Dorsal root ganglia (DRG) are crucial in the initial events of the infection by RV since they can act as a gate for the viral entrance into the CNS. In the present study, we examined cell tropism of RV and the roles of neuronal cytoskeletal components in the production of viral nucleoprotein (N protein) using cultured nerve cells and non-neuronal cells from DRG of newborn mice. Our in vitro study demonstrated a low propagation rate of RV in nerve cells, susceptibility of non-neuronal cells to RV, and independence of cytoplasmic synthesis of viral N protein from the neuronal cytoskeleton. The present study also suggests that Schwann cells should be considered as another possible candidate supporting RV propagation.

The Japanese journal of veterinary research

0047-1917

2009

No DOI available

Failure in developing high-level visual functions after occipitoparietal lesions at an early age: a case study.

Previous functional magnetic resonance imaging (fMRI) studies have identified several regions in the ventral visual pathway that are specialized for processing faces, words and general objects. However, little is known about the origin of the functional selectivity of these regions. Here, we reported a pediatric patient who suffered a left occipitoparietal lesion in the first year after birth from a subdural hematoma. After the hematoma was removed at the age of six, the hemianopia in the right visual field was alleviated, and no obvious deficits in low-level vision were observed in the patient at the age of twelve. In line with the behavioral observations, meridian mappings with fMRI showed that the early visual cortex of the left hemisphere was significantly activated, which was similar to that of the intact right hemisphere. However, the left ventral temporal cortex failed to show selective responses for faces, words and objects, which were in contrast to the normal selective responses for these objects in the right counterpart. Therefore, it is likely that the development of object selectivity in the ventral temporal cortex depends on visual inputs from the early visual cortex at an early age.

Cortex; a journal devoted to the study of the nervous system and behavior

1973-8102

2013

10.1016/j.cortex.2013.07.009

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

Brain : a journal of neurology

1460-2156

2023

10.1093/brain/awac090

Mechanisms of action of non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's disease.

Alzheimer's disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDs). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDs cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD subjects have failed, and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 pharmacogenomic effects and a real but delayed positive signal in a large primary prevention trial with naproxen. This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review.

CNS & neurological disorders drug targets

1996-3181

2010

10.2174/187152710791011991

New Japanese encephalitis vaccines: alternatives to production in mouse brain.

Japanese encephalitis virus (JEV), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito Culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of Asia. Resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. For the past several decades, killed viral vaccines prepared in tissue culture or mouse brain have been used effectively to immunize travelers and residents of enzootic countries. Cost, efficacy and safety concerns led to the development of a live-attenuated virus vaccine (SA14-14-2) and more recently, to the licensure in the USA, Europe, Canada, and Australia of a purified inactivated, tissue culture-based Japanese encephalitis vaccine (IXIARO(®), referred to as IC51; Intercell AG, Vienna, Austria). In addition, a live-attenuated yellow fever-Japanese encephalitis chimeric vaccine (IMOJEV™, referred to as Japanese encephalitis-CV; Sanofi Pasteur, Lyon, France) was recently licensed in Australia and is under review in Thailand. A broad portfolio of safe and effective Japanese encephalitis vaccines has become available to meet the needs of at-risk populations; when appropriately delivered, these new vaccines should greatly diminish the burden of disease.

Expert review of vaccines

1744-8395

2011

10.1586/erv.11.7

High risk of subacute sclerosing panencephalitis following measles outbreaks in Georgia.

To describe cases and estimate subacute sclerosing panencephalitis (SSPE) risk following large-sale measles outbreaks in Georgia. A rare, fatal late complication of measles, SSPE is often overlooked in assessments focused on the acute illness. Georgia had 8377 and 11,495 reported measles cases during the 2004-2005 and 2013-2015 outbreaks, respectively, but SSPE burden has not been assessed.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

1469-0691

2020

10.1016/j.cmi.2019.10.035

Genetics. Hybrid mosquitoes suspected in West Nile virus spread.

No abstract available

Science (New York, N.Y.)

1095-9203

2004

10.1126/science.303.5663.1451a

Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope.

The role of JC virus (JCV)-specific CTL was explored in the immunopathogenesis of progressive multifocal leukoencephalopathy (PML). We identified a 9-aa epitope of the JCV capsid protein VP1, the VP1(p100) peptide ILMWEAVTL, which is recognized by CTL of HLA-A2+ HIV+/PML survivors. We then constructed an HLA-A*0201/VP1(p100) tetrameric complex that allowed us to assess by flow cytometry the PBMC of 13 PML patients and 11 control subjects for the presence of JCV-specific CTL. VP1(p100)-specific CTL were detected by tetramer binding in VP1(p100)-stimulated PBMC of five of seven (71%) PML survivors and zero of six PML progressors (p = 0.02). Two of three HIV+ patients with a leukoencephalopathy resembling PML, but with no virologic evidence of JCV infection, also had detectable VP1(p100)-specific CTL in their PBMC. PBMC of eight HIV+ patients with other neurologic diseases and healthy control subjects had no detectable JCV-specific CTL. These data suggest that the JCV-specific cellular immune response may be important in the containment of PML, and the tetramer-staining assay may provide a useful prognostic tool in the clinical management of these patients.

Journal of immunology (Baltimore, Md. : 1950)

0022-1767

2002

10.4049/jimmunol.168.1.499

Infectious disease. Bird advocates fear that West Nile virus could silence the spring.

No abstract available

Science (New York, N.Y.)

1095-9203

2002

10.1126/science.297.5589.1989

Nucleic acid-based inhibition of flavivirus infections.

The genus Flavivirus in the family Flaviviridae consists of many arthropod-transmitted human pathogens, including dengue, yellow fever, Japanese encephalitis, West Nile, St. Louis encephalitis, Murray Valley encephalitis, and tick-borne encephalitis viruses. Treatment options against flaviviral disease are extremely limited, with no effective drugs yet commercially available. Recent advances in virology, synthetic organic chemistry, and the discovery of RNA interference (RNAi), have provided the basis for advances in the development of antisense-based approaches to address flaviviral infections. Oligomers of various antisense structural types, targeted to different locations in the flaviviral RNA genome, have now been used to successfully suppress viral gene expression and thereby inhibit flavivirus replication. Double-stranded RNA, containing viral sequence and designed to induce the endogenous cellular machinery of RNAi, has also been shown capable of potently interfering with flavivirus production and transmission. These studies provide insights into flaviviral molecular biology and the basis for the development of novel therapeutic approaches. The goal of this review is to summarize the findings of many of the significant reports that have appeared on the topic of antisense-mediated strategies for the development of antiviral therapy for flaviviruses.

Frontiers in bioscience : a journal and virtual library

1093-9946

2008

10.2741/2769

High vaccination coverage and inadequate knowledge: Findings from a community-based cross-sectional study on Japanese Encephalitis in Yangon, Myanmar.

<b>Background:</b> Japanese encephalitis (JE) is a mosquito-borne disease with high case fatality and no specific treatment. Little is known about the community's (especially parents/guardians of children) awareness regarding JE and its vaccine in Yangon region, which bears the highest JE burden in Myanmar. <b>Methods:</b> We conducted a community-based cross-sectional study in Yangon region (2019) to explore the knowledge and perception of parents/guardians of 1-15 year-old children about JE disease, its vaccination and to describe JE vaccine coverage among 1-15 year-old children. We followed multi-stage random sampling (three stages) to select the 600 households with 1-15 year-old children from 30 clusters in nine townships. Analyses were weighted (inverse probability sampling) for the multi-stage sampling design. <b>Results:</b> Of 600 parents/guardians, 38% exhibited good knowledge of JE <b>,</b> 55% perceived JE as serious in  children younger than 15 years and 59% perceived the vaccine to be effective <b>.</b> Among all the children in the 600 households, the vaccination coverage was 97% (831/855). <b>Conclusion:</b> In order to reduce JE incidence in the community, focus on an intensified education program is necessary to sustain the high vaccine coverage in the community.

F1000Research

2046-1402

2020

10.12688/f1000research.21702.3

Antiamoeboid activity of squamins C-F, cyclooctapeptides from Annona globifora.

Free-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C-F (1-4), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga, A. quina, and A. griffini, and a structure-activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D (2) and F (4), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C-F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC₉₀ for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.

International journal for parasitology. Drugs and drug resistance

2211-3207

2021

10.1016/j.ijpddr.2021.08.003

[Acute disseminated encephalomyelitis in childhood. Report of 10 cases].

Acute disseminated encephalomyelitis (ADEM) is a postinfectious encephalitis that is usually preceded by an infectious disease or vaccination. The clinical presentation has a wide spectrum and complementary exams are none specific, except magnetic resonance imaging (MRI) findings showing multifocal white-matter lesions similar to those seen en multiple sclerosis.

Revista de neurologia

0210-0010

No publication year available

No DOI available

Pathology in Practice.

No abstract available

Journal of the American Veterinary Medical Association

1943-569X

2018

10.2460/javma.253.11.1417

[Other Central Nervous System Infections(Including Fungal Infection, Tuberculosis, and Parasitic Infection)].

This review describes cryptococcal meningoencephalitis, tuberculous meningitis, neurosyphilis, and toxoplasma encephalitis. Central nervous system infections are neurological emergencies associated with mortality or other outcomes. Therefore, early diagnosis and treatment are critical. Fungal or gondii infections are rare and affect compromised hosts who are HIV positive, have diabetes, or take immunosuppressive or anticancer drugs. Cryptococcal antigens in the serum and cerebrospinal fluid are useful for the diagnosis of cryptococcal meningoencephalitis. RPR and TPHA tests are useful for the diagnosis of neurosyphilis. Cryptococcal meningoencephalitis and tuberculous meningitis often develop into hydrocephalus, making VP shunt necessary. Antifungal drugs for cryptococcal meningitis are limited by the blood-brain barrier, making a full recovery difficult; in such situations, intraventricular antifungal treatment is required.

No shinkei geka. Neurological surgery

0301-2603

2022

10.11477/mf.1436204654

Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice.

The present study assessed the influence of dietary lipids on accumulation of amyloid beta-peptide (Abeta) in the brain. Seven experimental diets with varying n-6/n-3-ratio, saturated and polyunsaturated fatty acid and cholesterol contents were fed to transgenic APPswe/PS1dE9 mice for 3-4 months beginning at a young adult age (6 months). Hippocampal Abeta levels were determined with ELISA and plaque load by using immunocytochemistry. A typical Western diet with 40% saturated fatty acids and 1% of cholesterol increased, while diets supplemented with docosahexaenoic acid (DHA) decreased Abeta levels compared to regular (soy oil based) diet. DHA diet also decreased the number of activated microglia in hippocampus and increased exploratory activity of transgenic mice, but did not improve their spatial learning in the water maze. The favorable effect of DHA on Abeta production was verified in two different cell lines. Regulation of dietary lipid intake may offer a new tool to reduce the risk of Alzheimer's disease at the population level.

Neurobiology of disease

0969-9961

2006

10.1016/j.nbd.2006.04.013

More on PML in Patients Treated with Dimethyl Fumarate.

No abstract available

The New England journal of medicine

1533-4406

2016

10.1056/NEJMc1512228

A Case of Disseminated Cutaneous Herpes Simplex Virus-1 as the First Manifestation of Human Immunodeficiency Virus Infection.

Reported clinical manifestations of active herpes simplex virus type 1 (HSV-1) infection include typically painful vesicular cutaneous rash in a dermatomal distribution, temporal lobe encephalitis, and rarely, fulminant septic shock with multiorgan failure. In immunocompromised patients, the cutaneous rash can become disseminated. We report a case of a 33-year-old male patient with undiagnosed human immunodeficiency virus (HIV) infection who presented to our emergency department (ED) with a disseminated cutaneous rash. The rash was extensive, involved 90% of his total body surface area. It began 5 days prior as small ulcerations localized to the left arm, sought care at an outside ED, diagnosed as severe dermatitis with bacterial superinfection and discharged with a cephalexin prescription. Laboratory results were positive for HIV test with a CD4 count of 254, white blood cell count (WBC) of 7.4 k/microL with 54% neutrophils, 9% lymphocytes, 0% eosinophils, 0% basophils, and serum creatinine and sodium of 3.05 mg/dL and 119 mEq/L, respectively. The burn team and dermatology ruled out Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis due to the absence of mucosal involvement, negative nikolsky sign, and absence of skin sloughing. Polymerase chain reaction of samples obtained from the skin lesions was positive for HSV-1. The rash resolved with intravenous acyclovir and was started on highly active antiretroviral therapy (HAART) on outpatient follow-up. To the best of our knowledge, comparable cases of significantly disseminated cutaneous HSV-1 infection as the initial presentation of HIV infection have been rarely reported.

Journal of investigative medicine high impact case reports

2324-7096

2021

10.1177/23247096211045245