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PubMed1998

Does glutamate mediate brain damage in acute encephalitis?

Cerebrospinal fluid (CSF) amino acid neurotransmitter concentrations in 23 patients with acute encephalitis were compared with those in patients with acute brain infarction, multiple sclerosis and controls. The concentration of glutamate was significantly higher in encephalitis (5.2+/-6.7 micromol/l) and stroke patients (9.6+/-14.2 micromol/l) than in MS patients (1.6+/-0.9 micromol/l) and controls (1.7+/-0.8 micromol/l; p < 0.001). The concentration of glycine was significantly higher in encephalitis (11.0+/-4.7 micromol/l) than in stroke (7.6+/-3.2 micromol/l) and MS patients (6.3+/-2.1 micromol/l) or controls (5.6+/-1.8 micromol/l; p < 0.002). Taurine levels were significantly lower in encephalitis patients than in the other groups (p = 0.04). The correlation of high glutamate levels with poor outcome was almost significant (Kendall tau 0.63, p = 0.06). Our observations suggest that exicitotoxic neurotransmission may play an important role in the series of events that lead to neuronal damage in encephalitis.

Adult↗

PubMed2005

Neurologic, neuropsychologic, and electroencephalographic findings after European tick-borne encephalitis in children.

Tick-borne European early summer meningoencephalitis is believed to be a benign disease in childhood. The causative RNA virus is from the same family as the West Nile virus, and the respective clinical presentations have many similarities. We studied 19 German children who had suffered from tick-borne encephalitis virus meningitis or meningoencephalitis in an endemic area and compared them with 19 matched controls. Epidemiologic data were consistent with known features of tick-borne encephalitis infection in southern Germany. None of the children studied had severe neurologic or neuropsychologic sequelae. One child developed significant clinical depression shortly after the illness. Electroencephalograms (EEGs) from children with tick-borne encephalitis were significantly slower on follow-up than control EEGs. After tick-borne encephalitis, children had a higher likelihood of having an impairment of attention and psychomotor speed. Using the Touwen neurologic examination, after tick-borne encephalitis, children had lower scores than control children on 4 of the 10 subsystems. Owing to the small sample size, it was difficult to identify risk factors for and predictors of adverse outcomes.

Adolescent↗

PubMed2026

Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings.

The primary aim of this study was to determine whether metagenomic next-generation sequencing (mNGS) can identify potential microbial agents responsible for encephalitis of unknown origin in immunocompetent patients, thereby enhancing clinical diagnostics. Cerebrospinal fluid samples from well-characterized patients (n = 17) diagnosed with encephalitis of unknown origin, according to Swedish national guidelines, were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections i.e. HSV-2 meningitis (n = 4), VZV CNS infections (n = 3), enterovirus meningitis (n = 2), JCV CNS infection (n = 2) were used as controls for the methodology (n = 11). No viral agents were detected in 16/17 CSF samples from patients with encephalitis of unknown etiology. 13/17 CSF samples were analysed for the most common autoimmune antibodies and were negative. In one CSF sample from patients with encephalitis of unknown origin a Human pegivirus (HPgV) was detected. In 9/11 control CSF samples from patients with CNS infections, RNA or DNA of the known virus were detected. The main conclusion in this study was that the negative results were related to that the majority of included patients were immunocompetent. The finding of HPgV in a patient with unknown encephalitis was judged as a bystander. However, mNGS might detect more pathogens in other patient cohorts and this study implicates that a close collaboration between the clinical laboratory and the clinicians enables a safe implementation of metagenomics.

Humans↗

PubMed2005

T-cells in human encephalitis.

Encephalitis literally means inflammation of the brain. In general, this inflammation can result from a viral or bacterial infection in the brain itself or alternatively from a secondary autoimmune reaction against an infection or a tumor in the rest of the body. Besides this, encephalitis is present in (believed autoimmune) diseases with unknown etiology, such as multiple sclerosis or Rasmussen encephalitis (RE). This article summarizes the existing data on the role of T-cells in the pathogenesis of three types of human encephalitis: RE, paraneoplastic encephalomyelitis, and virus encephalitis. In all of them, T-cells play a major role in disease pathogenesis, mainly mediated by major histocompatiblity complex class I-restricted CD8+ T-lymphocytes.

Encephalitis↗

PubMed2004

Non-herpetic acute limbic encephalitis: cerebrospinal fluid cytokines and magnetic resonance imaging findings.

OBJECTIVE: Non-herpetic acute limbic encephalitis (non-herpetic ALE) is regarded as a new subgroup of limbic encephalitis. In the present study, clinical findings and cerebrospinal fluid (CSF) cytokines in patients with non-herpetic ALE were investigated. PATIENTS AND METHODS: For adult inpatients in our hospital and related hospitals from 1996 to 2001, non-herpetic ALE was examined according to the criteria described in this study. Six patients were diagnosed as having non-herpetic ALE, and their clinical data and magnetic resonance imaging (MRI) were analyzed. In the CSF samples of the 6 patients with non-herpetic ALE and 6 patients with herpes simplex encephalitis (HSE), the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma were determined using sandwich-type enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The six patients with non-herpetic ALE showed all the acute encephalitis features, such as fever, altered consciousness, seizures, memory impairment, and mild CSF pleocytosis. MRI demonstrated selective abnormal signals in the limbic system, including the bilateral hippocampi and amygdalae. The levels of CSF IL-6 and IFN-gamma in patients with non-herpetic ALE were significantly lower than those in patients with HSE (p<0.05 and p<0.01, respectively). The levels of both TNF-alpha and IL-1beta were below the detection limits in both groups. CONCLUSION: Six patients were newly diagnosed as having non-herpetic ALE in this study. These patients revealed both acute limbic encephalitis and MRI abnormalities in the bilateral hippocampi and amygdalae. The levels of IL-6 and IFN-gamma in the CSF of patients with non-herpetic ALE were significantly lower than those of patients with HSE, possibly reflecting an immunological process in this type of ALE rather than direct viral infection.

Acute Disease↗

PubMed1998

A presumptive case of fatal Murray Valley encephalitis acquired in Alice Springs.

A presumptive case of Murray Valley Encephalitis (MVE) acquired in Alice Springs in March 1997 is reported. The patient subsequently died in Mackay. The diagnosis of Murray Valley Encephalitis was supported by the detection of flavivirus IgM in cerebrospinal fluid. Low titres of IgM specific to Murray Valley Encephalitis and Alfuy were detected in a single serum sample. The patient's travel movements indicate that his infection was acquired in the Alice Springs vicinity. This conclusion was further supported by the detection of Murray Valley Encephalitis activity in sentinel animals in the area and by the presence of large numbers of the principal mosquito vector of Murray Valley Encephalitis in the Northern Territory.

Antibodies, Viral↗

PubMed1999

An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys.

Placebo-controlled field efficacy trials of new Japanese encephalitis (JE) vaccines may be impractical. Therefore, an animal model to evaluate efficacy of candidate JE vaccines is sought. Previous work has shown that exposure of monkeys to JE virus (JEV) via the intranasal route results in encephalitis. Here we report the further development of this model and the availability of titered virus stocks to assess the protective efficacy of JE vaccines. To determine the effective dose of our JE challenge virus, dilutions of a stock JEV (KE-93 isolate) were inoculated into four groups of three rhesus monkeys. A dose-dependent response was observed and the 50% effective dose (ED50) was determined to be 6.0 x 10(7) plaque forming units (pfu). Among animals that developed encephalitis, clinical signs occurred 9-14 days postinoculation. Infection with JEV was confirmed by detection of JEV in nervous tissues and IgM to JEV in the cerebrospinal fluid. Viremia with JEV was also detected intermittently throughout infection. Validation of the model was performed using a known effective JE vaccine and saline control. One ED90 of virus (2.0 x 10(9) pfu) was used as a challenge dose. Four of four animals that received saline control developed encephalitis while one of four monkeys administered the JE vaccine did so. This study demonstrates that the virus strain, route of inoculation, dose, and the outcome measure (encephalitis) are suitable for assessment of protective efficacy of candidate JE vaccines.

Administration, Intranasal↗

PubMed2001

Outbreak of Powassan encephalitis--Maine and Vermont, 1999-2001.

Powassan (POW) virus, a North American tickborne flavivirus related to the Eastern Hemisphere's tickborne encephalitis viruses, was first isolated from a patient with encephalitis in 1958. During 1958-1998, 27 human POW encephalitis cases were reported from Canada and the northeastern United States. During September 1999-July 2001, four Maine and Vermont residents with encephalitis were found to be infected with POW virus. These persons were tested for other arbovirus infections found in the northeast after testing for West Nile virus (WNV) infection was negative. This report describes these four cases, summarizes the results of ecologic investigations, and discusses a potential association between ticks that infest medium-sized mammals and the risk for human exposure to POW virus. The findings underscore the need for personal protective measures to prevent tick bites and continued encephalitis surveillance.

Aged↗

PubMed2002

Simultaneous detection of three mosquito-borne encephalitis viruses (eastern equine, La Crosse, and St. Louis) with a single-tube multiplex reverse transcriptase polymerase chain reaction assay.

Three mosquito-borne human encephalitis viruses (eastern equine encephalitis virus [EEE], St. Louis encephalitis virus [SLE], and La Crosse encephalitis virus [LAC]) are sympatric in the southeastern United States. However, little is known concerning the temporal and spatial pattern of the distribution of these viruses in this area. As part of surveillance activities to detect the transmission of these 3 viruses in the Tennessee Valley area, we developed a single-tube multiplex reverse transcriptase polymerase chain reaction (RT-PCR) assay capable of detecting these 3 mosquito-borne viruses in a single reaction. Three viruses were differentiated by size of amplified products. Sensitivities of the multiplex RT-PCR assay for SLE, EEE, and LAC were 1-3 log median tissue culture infective doses per pool, roughly comparable to the reported sensitivity of PCR detection assays for the individual viruses, and 1 log more sensitive than antigen-capture assays for SLE and EEE. The sensitivity of the multiplex PCR was not changed significantly when carried out in the presence of extracts prepared from 50 uninfected mosquitoes. The cost of the assay is estimated at $2.98 per test, similar to the cost of other RT-PCR-based assays for viruses. However, adaptation of the RT-PCR to a multiplex format adds less than $0.01 to the per-unit cost of an RT-PCR assay targeting a single virus species. Analysis of these data suggests that the single-tube multiplex RT-PCR assay represents a sensitive, specific, cost-effective, and rapid method for monitoring activities of the 3 endemic mosquito-borne human encephalitis viruses in mosquito populations in the southeastern United States.

Animals↗

PubMed1992

Study of the outbreak of Japanese encephalitis in Lakhimpur district of Assam in 1989.

An outbreak of Japanese encephalitis was reported from Lakhimpur district of Assam in July-August, 1989. The outbreak affected 90 villages of the district, covering a population of approximately 36,000. There were 140 cases and 70 deaths due to the epidemic, giving a case fatality rate of 50%. There were no cases from Gogamukh area of the district, where a pilot Japanese encephalitis vaccination project was conducted in the population between July-August 1987, with Kasauli Japanese encephalitis vaccine. Serological examination of acute and convalescent cases showed Japanese encephalitis specific IgM indicating strong evidence of recent Japanese encephalitis infection.

Disease Outbreaks↗

PubMed1992

Detection and differentiation of dengue-1 from Japanese encephalitis virus infections by ABC MAC-ELISA.

An IgM antibody capture enzyme linked immunosorbent assay using avidin biotin complex system (ABC MAC-ELISA) was established for the detection and differentiation of dengue-1 and Japanese encephalitis virus infections. The cut-off value of MAC-ELISA was based on the mean value of optical density at 490 nm of seven negative human sera carried along in each assay multiplied by 2.1. The specificity of MAC-ELISA tested on 200 healthy enrolled male serum was 99.5% and 98.0% for dengue-1 and Japanese encephalitis IgM, respectively. Two hundred and sixty-six acute or followed-up dengue serum specimens which were identified to possess dengue-1 virus by virus isolation technique using C6/36 cell line and monoclonal antibody immunofluorescent assay (IFA) were tested by MAC-ELISA for IgM antibodies to dengue-1 and Japanese encephalitis virus infection. The positivity of IgM antibody for serum collected from day 1 to day 7 after onset of the disease was 0.0%, 0.0%, 7.6% 14.2%, 25.0%, and 77.7% by each consecutive day, correspondingly, for those collected from day 8 to two month was 96.7% overall. By comparison the P/N value of dengue-1 IgM to JE IgM, 98.5% and 96.8% of the dengue-1 and Japanese encephalitis suspected serum specimens could be distinguished from each other, respectively. MAC-ELISA is a convenient, rapid, sensitive and specific method for the detection and differentiation of dengue-1 from Japanese encephalitis virus infections.

Antibodies, Viral↗

PubMed2005

[Meningitis and encephalitis in Poland in 2003].

In Poland, 829 cases of bacterial meningitis and encephalitis, 563 cases of viral encephalitis, 973 of viral meningitis and 300 cases of meningitis and encephalitis of other or unknown etiology were reported in 2003. Incidence of the bacterial central nervous system infections has been declining over the past decade and the level of viral infections other then tick-borne encephalitis, following the outbreak in the mid-nineties, remained stable. Etiological factor was determined in 352 (42%) cases of bacterial meningitis/encephalitis. Among them Neisseria meningitidis was found in 76 cases, Haemophilus influenzae in 68 cases and Streptococcus pneumoniae in 91 cases. As in the past type B was the predominant type of N. meningitidis cultured from the patients, but type C appears to be on the rise accounting for 36% of the strains serotyped in 2003. Tick borne encephalitis increased markedly in 2003, with the highest ever noted number of cases (339). Most of the cases were reported from endemic areas of north-eastern part of the country.

Adolescent↗

PubMedDate not supplied

[Epidemiology of encephalitis caused by arbovirus in the Brazilian Amazonia].

An overview of ecological, epidemiological and clinical findings of potential arthropod-borne encephalitis viruses circulating in the Amazon Region of Brazil are discussed. These viruses are the Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), St. Louis Encephalitis (SLE), Mucambo (MUC) and Pixuna (PIX). These last two are subtypes (III and IV) of Venezuelan Equine Encephalitis virus. The areas of study were the highways and projects of development, as well as places where outbreaks of human diseases caused by arboviruses had been detected. These viruses are widespread in all Amazonia, and at least four of them, EEE, WEE, SLE and MUC are pathogenic to man. EEE and WEE infections were detected by serology, while SLE and MUC by either serology and virus isolation. The PIX virus has the lowest prevalence and, it was isolated in only a few cases, one being from a laboratory infection. Wild birds are the main hosts for all these viruses, except MUC, whose major hosts are rodents. The symptoms presented by infected people were generally a mild febrile illness. Although, jaundice was observed in two individuals from whom SLE was isolated. A comparison of the clinical symptoms presented by the patients in the Amazon Region and other areas of America, especially in the USA is made. In Brazilian Amazon region epidemics have not been detected although, at least, one EEE epizootic was recorded in Bragança, Para State, in 1960. At that time, of 500 horses that were examined 61% were positive to EEE by HI and of them 8.2% died. On the other hand, SLE has caused four epizootics in a forest near Belem. Wild birds and sentinel monkeys were infected, but no human cases were reported.

Animals↗

PubMed1990

[Acute non-suppurative encephalitis in children].

From July 1973 to January 1988, 66 children aged from three months to 14 years, 36 boys and 29 girls, were seen at the Central Hospital, Viborg, with acute encephalitis. In 25 cases the encephalitis was caused by mumps, in eight by measles, in six by chicken pox, one by herpes simplex, one by RS-virus, and one by mycoplasma. One case was seen after vaccination, one after infection and in 22 cases the cause of the encephalitis remained unknown. Sequelae were seen in 17 cases. The risk of encephalitis after mumps, measles, and rubella is an important argument for the use of MMR-vaccination and the risk of encephalitis after chickenpox may justify a vaccination campaign against chickenpox.

Acute Disease↗

PubMed1982

Persistence of tick-borne encephalitis virus IV. Virus localization after intracerebral inoculation.

Tick-borne encephalitis (TBE) virus was isolated from the brains and spinal cords, blood, livers, lymph nodes and kidneys from Macaca rhesus monkeys showing acute and subacute fatal encephalitis. In subacute encephalitis, virus titres in the CNS were lower than in acute disease (3.0--6.2 against 3.8--8.3 log LD50/ml). TBE virus localization in chronic encephalitis was largely the same as in acute and subacute disease. In monkeys with a chronic course and stable paralysis of the upper extremity, infectious TBE virus was isolated on day 383 from subcortical ganglia and spinal cord. In lymph nodes and spleen, it could be detected only by a combination of methods (co-cultivation in association with fluorescent antibody technique and complement-fixation test, explantation of organ fragments) more sensitive than is the inoculation of mice with organ homogenates. TBE virus was detected by the same methods on day 90 in the CNS and internal organs of a monkey with chronic encephalitis in the stage of remission.

Animals↗

PubMedDate not supplied

[Role of Powassan virus in the etiological structure of tick-borne encephalitis in the Primorsky Kray].

Composite studies conducted annually in the Primorsky kray showed the tick-borne encephalitis virus to play the main etiological role in the group of encephalites with the spring-summer incidence. In 1976--1978, virological studies of 69 cases of the disease yielded 11 strains of tick-borne encephalitis virus. In 1978, from the blood of clinically normal woman after a tick bite strain 555 was first isolated which was identified as Powassan virus, and antigenemia was observed for 53 days using the fluorescent antibody technique. In the same period, serological examinations of the blood sera from 117 patients demonstrated antibody to tick-borne encephalitis virus in 69.2%, to Powassan virus in 4,3% and to both viruses simultaneously in 4.3%. Besides, antibody to tick-borne encephalitis virus, Powassan virus and both viruses simultaneously was found in patients with progredient forms of tick-borne encephalitis and in subjects with the history of tick attachment.

Antibodies, Viral↗

PubMedDate not supplied

[Variants of the host immune response to the tick-borne encephalitis virus].

Syrian hamsters intracerebrally infected with tick-borne encephalitis (TBE) virus were used to study the correlation between virulence of the strains, their serotype, form and course of the disease, average survival time (AST) of hamsters, features of CNS pathomorphology, and the changes of values of cell-mediated and humoral immunity. Thirty one strains of TBE virus isolated in Siberia and Far East were studied. Virulence of the strains ranged from 100% to 5%, AST from 5 to 237 days. Hamsters developed acute lethal encephalitis, subacute encephalitis, or asymptomatic infection. Most virulent strains produced early and extensive lesions in the brain stem. In encephalitis with subacute course pathomorphological changes in the CNS developed slower and the brain stem was less involved. Each variant of TBE course was associated with a certain pattern of host immune response formed as early as the first day of infection. Highly virulent strains inducing acute encephalitis and 100% lethality within 5-9 days produced immune response characterized by high antigen reactivity of lymphocytes by the level of rosette-forming cells, marked specific sensitization in splenocyte migration-inhibition test, moderate antibody-producing cell reaction, increased thymus weight index, low values of nonspecific resistance with low levels of antihemagglutinins and virus-neutralizing antibody by the end of the first week. Different immunologic condition was associated with asymptomatic infection and increase of AST to 100-237 days.

Animals↗

PubMed1979

Arboviruses in New York State: an attempt to determine the role of arboviruses in patients with viral encephalitis and meningitis.

In a reveiw of 2,963 patients with signs of infections of the central nervous system in New York State in 1966--1977, arboviruses were found to be the confirmed or presumptive etiologic agents in 60 patients. California encephalitis (CE) virus was the most common (44 patients), followed by Powassan (POW) virus (8), St. Louis encephalitis virus (7), and eastern equine encephalitis (EEE) virus (1). Most patients (47) were children. The incidence of encephalitis was higher in patients with arbovirus findings than in infections with any other of the common neurotropic viruses. The disease was fatal in two patients, one infected with POW virus, the other with EEE virus. Most patients with CE virus infections resided in suburban areas. All POW infections were contracted in six rural counties known for their recreational facilities.

Adolescent↗