encephalitis
Diagnosis, Diagnostics, Immunodiagnosis &
Immunodiagnostics:
3233. Abendroth A. Arvin AM. Immune evasion as a pathogenic
mechanism of varicella zoster virus. [Review] [70 refs] Seminars in
Immunology. 13(1):27-39, 2001 Feb.
Abstract
Varicella zoster virus (VZV) is a human herpesvirus that causes
varicella (chickenpox) during primary infection, establishes latency in dorsal
root ganglia and may reactivate years later, producing herpes zoster. VZV must
evade antiviral immunity during three important stages of viral pathogenesis,
including the cell-associated viremia characteristic of primary infection,
persistence in dorsal root ganglia during latency and the initial period of VZV
reactivation. Our observations about the immunomodulatory effects of VZV
document its capacity to interfere with adaptive immunity mediated by CD4 as
well as CD8 T cells, ensuring the survival of the virus in the human population
from generation to generation. Copyright 2001 Academic Press. [References: 70]
3234.
Awasthi M.
Parmar H. Patankar T. Castillo M.
Imaging findings in rabies encephalitis. Ajnr: American Journal of Neuroradiology. 22(4):677-80, 2001 Apr.
Abstract
SUMMARY: Rabies encephalitis is perhaps one of
the few infectious diseases that command attention and fear not only from the
layman but also from physicians. The unique mode of transmission, the virtually
exclusive neurotransmission shown by the agent, and the complete hopelessness
of the established disease sets rabies apart from other zoonoses transmitted to
man. Rabies encephalitis is a fatal disease and its diagnosis is usually based
on the clinical presentations and findings. Hence, imaging in rabies is seldom
done, and imaging findings in rabies encephalitis have rarely been described.
We present the imaging findings in two confirmed cases of rabies encephalitis
in which antemortem diagnosis was obtained by corneal impression smears showing
the presence of viral antigens. The differential diagnosis of the imaging
findings as well as the role and the relevance of imaging in the diagnosis of
this disease are discussed. The current literature on the subject is also
reviewed.
3235.
Bestetti A.
Pierotti C. Terreni M. Zappa A.
Vago L. Lazzarin A. Cinque P. Comparison of three nucleic acid
amplification assays of cerebrospinal fluid for diagnosis of cytomegalovirus
encephalitis. Journal of Clinical Microbiology. 39(3):1148-51, 2001 Mar.
Abstract
The diagnostic reliabilities of three
cytomegalovirus (CMV) nucleic acid amplification assays of cerebrospinal fluid
(CSF) were compared by using CSF samples from human immunodeficiency
virus-infected patients with a postmortem histopathological diagnosis of CMV
encephalitis (n = 15) or other central nervous system conditions (n = 16). By
using a nested PCR assay, the quantitative COBAS AMPLICOR CMV MONITOR PCR, and
the NucliSens CMV pp67 nucleic acid sequence-based amplification assay,
sensitivities were 93.3, 86.6, and 93.3%, respectively, and specificities were
93.7, 93.7, and 87.5%, respectively. The COBAS AMPLICOR assay revealed
significantly higher CMV DNA levels in patients with diffuse
ventriculoencephalitis than in patients with focal periventricular lesions.
3236.
Hinson VK.
Tyor WR. Update on viral encephalitis. [Review] [45 refs] Current Opinion in Neurology. 14(3):369-74, 2001 Jun.
Abstract
Over 100 viruses have been associated with
acute central nervous system infections. The present review focuses on some of
the most common agents of viral encephalitis, as well as important emerging
viral encephalitides. In this context, the initial detection of West Nile virus
in the Western Hemisphere during the 1999 New York City outbreak, the first
description of Nipah virus in Malaysia, and the appearance in Asia of a new
neurovirulent enterovirus 71 strain that causes severe neurologic disease are
highlighted. In addition, advances regarding diagnosis, neuroimaging and
treatment of Japanese and herpes simplex encephalitis are presented.
[References: 45]
3237.
Hooper P. Zaki S. Daniels P.
Middleton D. Comparative pathology of the diseases caused by Hendra and
Nipah viruses. [Review] [17 refs] Microbes & Infection. 3(4):315-22, 2001 Apr.
Abstract
Information on the pathogenesis and transmissibility of Hendra
and Nipah viruses was obtained by comparing their histopathology. Both viruses
induced syncytial cells in vascular tissues and they were primarily vasotropic
and/or neurotropic, generating interstitial pneumonia or encephalitis. Nipah
virus in pigs was also epitheliotropic in respiratory epithelium and thus
contagious. [References: 17]
3238.
Huang C.
Slater B. Campbell W. Howard J.
White D. Detection of arboviral RNA directly from mosquito homogenates
by reverse-transcription-polymerase chain
reaction. Journal of Virological Methods. 94(1-2):121-8, 2001 May.
Abstract
Many arthropod-borne viruses (arboviruses)
are important human pathogens medically. The development of an effective
technique to detect the viruses by using nucleic acid amplification, such as
polymerase chain reaction (PCR), improves not only clinical diagnosis but also
virologic surveillance of mosquito vectors in the field. In this study, the
development of an improved and simplified assay is described for detection of
mosquitoes infected with eastern equine encephalitis (EEE) virus, Cache Valley
(CV), and California (CAL) serogroup viruses from field-collected mosquito
pools. As little as 5 microl of homogenate from mosquito pools was used in the
reverse transcription (RT) reaction followed by the use of three sets of
specific primers for the PCR. Positive pools were determined by finding PCR
bands of the expected size for each arbovirus. The confirmation and
identification of Bunyaviruses was done by sequencing the PCR product. In 1999,
West Nile virus (WNV) was identified as the etiologic agent of an outbreak of
human encephalitis in New York City. It is shown that this protocol is also
able to detect West Nile viral RNA in a pool of 100 mosquitoes containing one
infected mosquito.
3239.
Singh P.
Kalra N. Ratho RK. Shankar S.
Khandelwal N. Suri S. Coexistent neurocysticercosis and Japanese B
encephalitis: MR imaging correlation.
Ajnr: American Journal of Neuroradiology. 22(6):1131-6, 2001 Jun-Jul.
Abstract
BACKGROUND AND PURPOSE: An increased incidence of intestinal
helminthic infections has been observed in patients with viral encephalitis in
endemic areas. Both Japanese B encephalitis (JE) and neurocysticercosis (NCC)
share some common socio-demographic and ecologic factors, and pigs act as the
intermediate carrier for both. Our purpose was to show the coexistence of JE
and NCC in brain on MR images and highlight the possible role of NCC as an
amplifier of JE. METHODS: MR images from 10 cases of coexistent JE and NCC were
studied retrospectively. T1-weighted axial and sagittal, proton T2-weighted
axial and coronal, and T2-weighted fluid-attenuated inversion recovery axial
and coronal sections of the brain were evaluated. NCC was diagnosed on the
basis of neuroimaging. Diagnostic serologic testing for JE was conducted using
paired blood and CSF samples. RESULTS: The JE changes were bilateral and
asymmetrical and were more severe on the side harboring the solitary cyst or
the side bearing the greater number of cysts or lodging the degenerating cyst.
In each of nine of 10 cases, at least one degenerating cyst was found on the
side of predominant JE pathologic abnormality. CONCLUSION: The study suggests
that the co-occurrence of JE and NCC is not just a chance coincidence. NCC
apparently predisposes a person to JE infection and is a positive modulator of
the encephalitic process. The study shows a spectrum of MR imaging findings of
coexistent JE and NCC.
4020.
Barrett AD. Current status of flavivirus
vaccines. Ann N Y Acad Sci 2001
Dec;951:262-71
Although
there are approximately 68 flaviviruses recognized, vaccines have been
developed to control very few human flavivirus diseases. Licensed live
attenuated vaccines have been developed for yellow fever (strain 17D) and
Japanese encephalitis (strain SA14-14-2) viruses, and inactivated vaccines have
been developed for Japanese encephalitis and tick-borne encephalitis viruses.
The yellow fever live attenuated 17D vaccine is one of the most efficacious and
safe vaccines developed to date and has been used to immunize more than 300
million people. A number of experimental vaccines are being developed, most
notably for dengue. Candidate tetravalent live attenuated dengue vaccines are
undergoing clinical trials. Other vaccines are being developed using reverse
genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow
fever 17D vaccine has been used as a backbone to generate chimeric viruses
containing the premembrane and envelope protein genes from other flaviviruses.
The "Chimerivax" platform has been used to construct chimeric
Japanese encephalitis and dengue viruses that are in different phases of
development. Similar strategies are being used by other laboratories.
4021.
Chang GJ, Davis BS, Hunt AR, Holmes DA, Kuno G.
Flavivirus DNA vaccines: current status and potential. Ann N Y Acad Sci 2001 Dec;951:272-85
The use of DNA-based vaccines is a novel and promising immunization approach for the development of flavivirus vaccines. This approach has been attempted in vaccine development for various virus species, including St. Louis encephalitis, Russian spring-summer encephalitis, Central European encephalitis, dengue serotypes 1 and 2, Murray Valley encephalitis, Japanese encephalitis, and West Nile viruses. However, very little is known about the factors affecting its efficacy. Recently, we demonstrated that a single intramuscular immunization of DNA vaccine of Japanese encephalitis and West Nile viruses protected mice and horses from virus challenge. Administration of these recombinant plasmid vectors resulted in endogenous expression and secretion of extracellular virus-like particles that correlated well with the induction of protective immunity. These results provided evidence that the virus-like particles composed of premembrane/membrane and envelope proteins are essential for eliciting immune responses similar to those induced by live, attenuated virus vaccines. The biosynthesis and protein processing of premembrane/membrane and envelope proteins that preserve the native conformation and glycosylation profiles identical to virion proteins could be determined by the effectiveness of the transmembrane signal sequence located at the amino-terminus of premembrane protein. The use of DNA vaccines in multivalent and/or combination vaccines designed to immunize against multiple flaviviruses is also a promising area of development.
4022.
Chiarugi A, Calvani M, Meli E, Traggiai E, Moroni
F. Synthesis and release of neurotoxic kynurenine metabolites by human
monocyte-derived macrophages. J Neuroimmunol
2001 Nov 1;120(1-2):190-8
We studied
the regulation of the kynurenine pathway of tryptophan metabolism in human
monocyte-derived macrophages (MDM) with the aim of evaluating macrophage
involvement in inflammatory neurological disorders.Cultured MDM metabolized
tryptophan and released kynurenine metabolites, including the excitotoxin
quinolinic acid (QUIN). Lipopolysaccharides (LPS) or the pro-inflammatory
cytokines INFgamma and TNFalpha increased, while IL 4 or IL 10 inhibited the
rate of tryptophan metabolism and the release of QUIN.The incubation media of
INFgamma-exposed MDM caused neuronal death in primary cultures of mixed
cortical cells. Glutamate receptor antagonists or poly(ADP-ribose) polymerase
inhibitors significantly reduced this death, thus suggesting new possibilities
for the treatment of neuronal damage in neuroinflammatory disorders.
4023.
Cuzzubbo AJ, Endy TP, Nisalak A, Kalayanarooj S,
Vaughn DW, Ogata SA, Clements DE, Devine PL. Use of recombinant envelope
proteins for serological diagnosis of Dengue virus infection in an
immunochromatographic assay. Clin Diagn Lab Immunol 2001 Nov;8(6):1150-5
An
immunochromatographic test that incorporates recombinant antigens (Dengue Duo
Rapid Strip Test; PanBio, Brisbane, Australia) has recently become commercially
available. This assay is performed in 15 min and detects both immunoglobulin M
(IgM) and IgG in a capture format. The four recombinant proteins used represent
the N-terminal 80% of the viral envelope glycoproteins of dengue viruses 1, 2,
3, and 4, respectively. The sensitivity and specificity of the recombinant
antigen-based assay were 90 and 86%, respectively. The similar diagnostic
performance of these antigens to that of enzyme-linked immunosorbent assays
using whole dengue virus suggests that they mimic whole dengue viruses in
primary structure and epitope conformation. These results suggest that
recombinant proteins can be used in diagnostic assays for dengue to overcome
safety issues associated with the use of whole virus.
4024.
Deubel V, Fiette L, Gounon P, Drouet MT, Khun H,
Huerre M, Banet C, Malkinson M, Despres P. Variations in biological features of
West Nile viruses. Ann N Y Acad Sci
2001 Dec;951:195-206
Pathological findings in humans, horses, and birds with West Nile (WN) encephalitis show neuronal degeneration and necrosis in the central nervous system (CNS), with diffuse inflammation. The mechanisms of WN viral penetration of the CNS and pathophysiology of the encephalitis remain largely unknown. Since 1996, several epizootics involving hundreds of humans, horses, and thousands of wild and domestic bird cases of encephalitis and mortality have been reported in Europe, North Africa, the Middle East, Russia, and the USA (see specific chapters in this issue). However, biological and molecular markers of virus virulence should be characterized to assess whether novel strains with increased virulence are responsible for this recent proliferation of outbreaks.
4025.
Hughes AJ, Daniel SE, Lees AJ. Improved accuracy
of clinical diagnosis of Lewy body Parkinson's disease. Neurology 2001 Oct 23;57(8):1497-9
The authors studied the accuracy of clinical diagnosis of idiopathic PD (IPD) in 100 consecutive clinically diagnosed cases that came to neuropathological examination. Ninety fulfilled pathologic criteria for IPD. Ten were misdiagnosed: multiple system atrophy (six), progressive supranuclear palsy (two), post-encephalitic parkinsonism (one), and vascular parkinsonism (one). Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria.
4026.
Konstantinou D, Paschalis C, Maraziotis T,
Dimopoulos P, Bassaris H, Skoutelis A. Two episodes of leukoencephalitis
associated with recombinant hepatitis B vaccination in a single patient. Clin Infect
Dis 2001 Nov 15;33(10):1772-3
Cases of central nervous system demyelination have been reported after recombinant hepatitis B vaccination, but no causal link has been clearly demonstrated. We present the first case report involving the occurrence of 2 episodes of leukoencephalitis in a previously healthy patient after vaccination and rechallenge with hepatitis B vaccine.
4027.
Leder K, Weller PF, Wilson ME. Travel vaccines
and elderly persons: review of vaccines available in the United States. Clin
Infect Dis 2001 Nov 1;33(9):1553-66
Aging is associated with alterations in immune responses and may lead to clinically significant changes in the safety, immunogenicity, and protective efficacy of certain vaccines. This review summarizes published data regarding the effects of age on responses after immunization with vaccines generally administered before travel. The specific vaccines discussed in detail include hepatitis A, typhoid, yellow fever, Japanese encephalitis, and rabies vaccines. There is some evidence of diminished serological responses to hepatitis A and rabies vaccines in older individuals. In addition, increased toxic effects following yellow fever vaccination in elderly recipients have recently been reported. However, many travel-related vaccines have never been studied specifically in elderly populations. Consideration of potential age-related differences in responses to travel vaccines is becoming increasingly important as elderly persons more frequently venture to exotic destinations.
4028.
Marth E, Kleinhappl B. Albumin is a necessary
stabilizer of TBE-vaccine to avoid fever in children after vaccination.
Vaccine 2001 Nov 12;20(3-4):532-7
A thiomersal-free and also an albumin-free tick-borne encephalitis-vaccine (TBE-vaccine) was developed. This vaccine was approved by the Austrian health authorities in the year 2000. Contrary to previous experience, 779 cases of fever attacks occurred following the first vaccination of children under 15 years of age. The induction of the immune system by different TBE virus (TBEV) vaccines (FSME-Immun [1999], Ticovac [2000] and FSME-Immun [2001] all from Baxter Hyland Immuno, Vienna) was compared in an in vitro immune stimulation test in order to find an explanation for the unexpected fever attacks. It was shown that only Ticovac, which contains no albumin as a stabilizer, can induce relative high amounts of TNF-alpha (P < or = 0.0001) and lower amounts of IL-1 beta (P < or = 0.05). Increase of both cytokines is first observed following an incubation of 4 h. The maximum is reached after 15 h. After 26 h, it has reverted to the original value. The course of concentration of both cytokines corresponds to the time of observed febrile phases. Albumin or immunoglobulin prevents a rise of cytokines so that it is recommended to add the albumin again to the vaccine.
4029.
Monath TP. Prospects for development of a vaccine
against the West Nile virus. Ann N Y Acad Sci
2001 Dec;951:1-12
Vaccination provides the ultimate measure for personal protection against West Nile disease. The development of a West Nile vaccine for humans is justified by the uncertainty surrounding the size and frequency of future epidemics. At least two companies (Acambis Inc. and Baxter/immuno) have initiated research and development on human vaccines. West Nile encephalitis has also emerged as a significant problem for the equine industry. One major veterinary vaccine manufacturer (Ft. Dodge) is developing formalin-inactivated and naked DNA vaccines. The advantages and disadvantages of formalin-inactivated whole virion vaccines, Japanese encephalitis vaccine for cross-protection, naked DNA, and live attenuated vaccines are described. A novel technology platform for live, attenuated recombinant vaccines (ChimeriVax) represents a promising approach for rapid development of a West Nile vaccine. This technology uses yellow fever 17D as a live vector for envelope genes of the West Nile virus. Infectious clone technology is used to replace the genes encoding the prM and E structural proteins of yellow fever 17D vaccine virus with the corresponding genes of West Nile virus. The resulting virion has the protein coat of West Nile, containing all antigenic determinants for neutralization and one or more epitopes for cytotoxic T lymphocytes. The genes encoding the nucleocapsid protein, nonstructural proteins, and untranslated terminal regions responsible for replication remain those of the original yellow fever 17D virus. The chimeric virus replicates in the host like yellow fever 17D but immunizes specifically
against West Nile virus.
4030.
Price P, Mathiot N, Krueger R, Stone S, Keane NM,
French MA. Immune dysfunction and immune restoration disease in HIV patients
given highly active antiretroviral therapy. J Clin Virol 2001 Oct;22(3):279-87
BACKGROUND: Some immune defects caused by HIV infection resolve following treatment with highly active antiretroviral therapy (HAART), but residual immune dysfunction may cause disease. Problems with the regulation of the restored immune system in the first six months of treatment can lead to atypical presentations of mycobacterial, cytomegalovirus (CMV), hepatitis B virus or hepatitis C virus (HCV) disease. We defined these conditions as immune restoration diseases (IRD) and showed that they occur in 30-40% of individuals who begin HAART from low CD4 T cell counts. OBJECTIVES: Analysis of immune dysregulation in patients who have responded to HAART. STUDY DESIGN: Patients with successful immune reconstitution following HAART were selected from a database containing details of all patients managed at Royal Perth Hospital (Western Australia) on the basis a CD4 T cell count <100/microl before HAART and an increase of >4-fold or to >200 CD4 T cells/microl. RESULTS: Patients who had experienced an IRD demonstrated increased levels of bioavailable IL-6 and increased expression of CCR5 and CCR3 on monocytes and granulocytes, but numbers of gammadeltaT-cells were similar to patients with similar CD4 T cell counts without an IRD. Carriage of HLA-A2, -B44 was associated with a history of CMV retinitis and/or encephalomyelitis as an IRD, but not with IRD initiated by Mycobacterium sp., cutaneous varicella zoster or herpes simplex infections or HCV. We also identified a patient with Graves' thyrotoxicosis and pronounced lymphadenopathy after HAART, and demonstrated that thyroid stimulating hormone receptor antibody production was associated with an increase in serum soluble CD30, suggesting acquired immune dysregulation. CONCLUSIONS: IRD are associated with persistent immune activation, where differences in genetic profiles suggest that distinct pathological mechanisms are responsible for retinitis/encephalomyelitis IRD. Further studies are important as dysregulated T-cell responses may cause disease later in the course of immune reconstitution.
4031.
Razonable RR, Aksamit AJ, Wright AJ, Wilson JW.
Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient
receiving highly active antiretroviral therapy. Mayo Clin Proc 2001 Nov;76(11):1171-5
Progressive multifocal leukoencephalopathy (PML), a frequently fatal demyelinating disease caused by JC virus, occurs as an opportunistic infection in patients with acquired immunodeficiency syndrome. Curative therapy has been elusive, but recent reports suggest its improvement after institution of highly active antiretroviral therapy (HAART). We describe a case of PML that developed 6 months after the patient, a 55-year-old man, began to receive HAART. The PML progressed despite good virologic and immunologic response to HAART. Substantial symptomatic and radiographic improvement occurred after the addition of cidofovir to the treatment regimen. We reviewed the scientific literature on this rare occurrence of PML after institution of HAART and describe the patient characteristics, potential pathogenesis, and therapeutic options, including the successful use of cidofovir as an adjunctive agent.
4032.
Roehrig JT, Staudinger LA, Hunt AR, Mathews JH,
Blair CD. Antibody prophylaxis and therapy for flavivirus encephalitis
infections. Ann N Y Acad Sci 2001
Dec;951:286-97
The outbreak of West Nile (WN) encephalitis in the United States has rekindled interest in developing direct methods for prevention and control of human flaviviral infections. Although equine WN vaccines are currently being developed, a WN vaccine for humans is years away. There is also no specific therapeutic agent for flaviviral infections. The incidence of human WN virus infection is very low, which makes it difficult to target the human populations in need of vaccination and to assess the vaccine's economic feasibility. It has been shown, however, that prophylactic application of antiflaviviral antibody can protect mice from subsequent virus challenge. This model of antibody prophylaxis using murine monoclonal antibodies (MAbs) has been used to determine the timing of antibody application and specificity of applied antibody necessary for successful prophylaxis. The major flaviviral antigen is the envelope (E) glycoprotein that binds cellular receptors, mediates cell membrane fusion, and contains an array of epitopes that elicit virus-neutralizing and nonneutralizing antibodies. The protective efficacy of an E-glycoprotein-specific MAb is directly related to its ability to neutralize virus infectivity. The window for successful application of prophylactic antibody to prevent flaviviral encephalitis closes at about 4 to 6 days postinfection concomitant with viral invasion of the brain. Using murine MAbs to modify human disease results in a human antimouse antibody (HAMA) response that eventually limits the effectiveness of subsequent murine antibody applications. To reduce the HAMA response and make these MAbs more generally useful for humans, murine MAbs can be "humanized" or human MAbs with analogous reactivities can be developed. Antiflaviviral human or humanized MAbs might be practical and cost-effective reagents for preventing or modifying flaviviral diseases.
4033.
Seo SK, Regan A, Cihlar T, Lin DC, Boulad F,
George D, Prasad VK, Kiehn TE, Polsky B. Cytomegalovirus ventriculoencephalitis
in a bone marrow transplant recipient receiving antiviral maintenance: clinical
and molecular evidence of drug resistance. Clin Infect Dis 2001 Nov 1;33(9):e105-8
We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.
4034.
Wang T, Anderson JF, Magnarelli LA, Bushmich S,
Wong S, Koski RA, Fikrig E. West Nile virus envelope protein: role in diagnosis
and immunity. Ann N Y Acad Sci 2001
Dec;951:325-7
The role of antibodies to the West Nile virus envelope (E) protein in serodiagnosis and protection was examined. The E protein was expressed and purified in recombinant form. Antibodies to the E protein were detected in patients with West Nile virus infection. Passive immunization with rabbit anti-E protein sera also partially protected mice from challenge with West Nile virus. The humoral response to the West Nile virus E protein is therefore useful as an aid in the diagnosis and may also play a role in immunity to infection.
4035.
Wong SC, Ooi MH, Wong MN, Tio PH, Solomon T,
Cardosa MJ. Late presentation of Nipah virus encephalitis and kinetics of the
humoral immune response. J Neurol Neurosurg Psychiatry 2001 Oct;71(4):552-4
Nipah virus is a newly discovered paramyxovirus
transmitted directly from pigs to humans. During a large encephalitis outbreak
in Malaysia and Singapore in 1998-9, most patients presented acutely. A 12 year
old child is described who developed encephalitis 4 months after exposure to
the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent
assay (ELISA), which is also described. The late presentation and IgG subclass
responses had similarities to subacute sclerosing panencephalitis. Nipah virus
should be considered in patients with encephalitis even months after their
possible exposure.
4567. Baric
RS, Yount B, Lindesmith L, Harrington PR, Greene SR, Tseng FC, Davis N, Johnston
RE, Klapper DG, Moe CL. Expression and self-assembly of norwalk virus capsid
protein from Venezuelan equine encephalitis virus replicons. J Virol. 2002
Mar;76(6):3023-30.
The Norwalk virus (NV) capsid protein was expressed using Venezuelan equine encephalitis virus replicon particles (VRP-NV1). VRP-NV1 infection resulted in large numbers of recombinant NV-like particles that were primarily cell associated and were indistinguishable from NV particles produced from baculoviruses. Mutations located in the N-terminal and P1 domains of the NV capsid protein ablated capsid self-assembly in mammalian cells.
4568. Brault
AC, Powers AM, Holmes EC, Woelk CH, Weaver SC. Positively charged amino acid
substitutions in the e2 envelope glycoprotein are associated with the emergence
of venezuelan equine encephalitis virus. J Virol. 2002 Feb;76(4):1718-30.
Epidemic-epizootic Venezuelan equine encephalitis (VEE) viruses (VEEV) have emerged repeatedly via convergent evolution from enzootic predecessors. However, previous sequence analyses have failed to identify common sets of nucleotide or amino acid substitutions associated with all emergence events. During 1993 and 1996, VEEV subtype IE epizootics occurred on the Pacific Coast of the states of Chiapas and Oaxaca in southern Mexico. Like other epizootic VEEV strains, when inoculated into guinea pigs and mice, the Mexican isolates were no more virulent than closely related enzootic strains, complicating genetic studies of VEE emergence. Complete genomic sequences of 4 of the Mexican strains were determined and compared to those of closely related enzootic subtype IE isolates from Guatemala. The epizootic viruses were less than 2% different at the nucleotide sequence level, and phylogenetic relationships confirmed that the equine-virulent Mexican strains probably evolved from enzootic progenitors on the Pacific Coast of Mexico or Guatemala. Of 35 amino acids that varied among the Guatemalan and Mexican isolates, only 8 were predicted phylogenetically to have accompanied the phenotypic change. One mutation at position 117 of the E2 envelope glycoprotein, involving replacement of Glu by Lys, resulted in a small-plaque phenotype characteristic of epizootic VEEV strains. Analysis of additional E2 sequences from representative enzootic and epizootic VEEV isolates implicated similar surface charge changes in the emergence of previous South American epizootic phenotypes, indicating that E2 mutations are probably important determinants of the equine-virulent phenotype and of VEE emergence. Maximum-likelihood analysis indicated that one change at E2 position 213 has been influenced by positive selection and convergent evolution of the epizootic phenotype.
4569. Chiappini
E, Calabri G, Galli L, Salvi G, de Martino M. Varicella-zoster virus acquired
at 4 months of age reactivates at 24 months and causes encephalitis. J Pediatr.
2002 Feb;140(2):250-1.
Varicella-zoster virus (VZV) reactivation in the brain caused encephalitis in a 2-year-old immunocompetent child who had chickenpox 20 months before. Radiologic findings were consistent with large to medium-vessel-vasculitis. VZV-DNA was detected in cerebrospinal fluid. Early acquisition of VZV may predispose to major neurologic complications that can occur years after the primary infection.
4570. D'Aversa
TG, Weidenheim KM, Berman JW. CD40-CD40L interactions induce chemokine
expression by human microglia: implications for human immunodeficiency virus
encephalitis and multiple sclerosis. Am J Pathol. 2002 Feb;160(2):559-67.
CD40 is a protein on microglia that is up-regulated with interferon (IFN)-gamma and is engaged by CD40L, found on CD4+ T cells, B cells, and monocytes. These interactions may be important in central nervous system inflammatory diseases. Microglia have been shown to be a source of chemokines, whose expression plays a key role in central nervous system pathologies. We examined the expression of CD40 on microglia in human immunodeficiency virus (HIV) encephalitic brain, and the effects of CD40-CD40L interactions on the expression of chemokines by cultured microglia. We found significantly increased numbers of CD40-positive microglia in HIV-infected brain tissue. Treatment of cultured microglia with IFN-gamma and CD40L increased expression of several chemokines. IFN-gamma- and CD40L-induced MCP-1 protein was mediated by activation of the ERK1/2 MAPK pathway, and Western blot analysis demonstrated phosphorylation of ERK1/2 upon stimulation of microglia. In contrast, IFN-gamma- and CD40L-induced IP-10 protein production was mediated by the p38 MAPK pathway. Our data suggest a mechanism whereby CD40L+ cells can induce microglia to secrete chemokines, amplifying inflammatory processes seen in HIV encephalitis and multiple sclerosis, and implicate CD40-CD40L interactions as a target for interventional strategies.
4571. del Mar
Mosquera M, de Ory F, Moreno M, Echevarria JE. Simultaneous detection of
measles virus, rubella virus, and parvovirus B19 by using multiplex PCR. J Clin
Microbiol. 2002 Jan;40(1):111-6.
We describe here a multiplex reverse transcription-PCR (RTMNPCR) assay designed to detect and differentiate measles virus, rubella virus, and parvovirus B19. Serial dilution experiments with vaccine strains that compared cell culture isolation of measles in B95 cells and rubella in RK13 cells showed sensitivity rates of 0.004 50% tissue culture infective dose (TCID(50)) for measles virus and 0.04 TCID(50) for rubella virus. This RTMNPCR can detect as few as 10 molecules for measles virus and rubella virus and one molecule for parvovirus B19 in dilution experiments with plasmids containing inserts of the primary reaction amplification products. Five pharyngeal exudates from measles patients and 2 of 15 cerebrospinal fluid samples from measles-related encephalitis were found to be positive for measles virus by this RTMNPCR. A total of 3 of 27 pharyngeal exudates from vaccinated children and 2 pharyngeal exudates, plus one urine sample from a case of congenital rubella syndrome, were found to be positive for rubella virus by RTMNPCR, whereas 16 of 19 sera from patients with erythema infectiosum were determined to be positive for parvovirus B19 by RTMNPCR. In view of these results, we can assess that this method is a useful tool in the diagnosis of these three viruses and could be used as an effective surveillance tool in measles eradication programs.
4572. Garg
RK. Subacute sclerosing panencephalitis. Postgrad Med J. 2002
Feb;78(916):63-70. Review.
Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence. It is caused by persistent defective measles virus. Brain biopsies or postmortem histopathological examination show evidence of astrogliosis, neuronal loss, degeneration of dendrites, demyelination, neurofibrillary tangles, and infiltration of inflammatory cells. Patients usually have behavioral changes, myoclonus, dementia, visual disturbances, and pyramidal and extrapyramidal signs. The disease has a gradual progressive course leading to death within 1-3 years. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of raised antibody titre against measles in the plasma and cerebrospinal fluid. Treatment for SSPE is still undetermined. A combination of oral isoprinosine (Inosiplex) and intraventricular interferon alfa appears to be the best effective treatment. Patients responding to treatment need to receive it life long. Effective immunisation against measles is the only solution presently available to the problem of this dreaded disease.
4573. Gupta
A, Prayson RA. Pathologic quiz case: a 3-year-old boy with new-onset partial
seizures. Arch Pathol Lab Med. 2002 Mar;126(3):379-80. No abstract available.
4574. Jackson
AC, Melanson M, Rossiter JP. Familial herpes simplex encephalitis. Ann Neurol.
2002 Mar;51(3):406-7. No abstract
available.
4575. Jordan-Sciutto
KL, Wang G, Murphey-Corb M, Wiley CA.
Cell cycle proteins exhibit altered expression patterns in
lentiviral-associated encephalitis. J Neurosci. 2002 Mar 15;22(6):2185-95.
Cell cycle proteins regulate processes as diverse as cell division and cell death. Recently their role in neuronal death has been reported in several models of neurodegeneration. We have reported previously that two key regulators of the cell cycle, the retinoblastoma susceptibility gene product (pRb) and transcription factor E2F1, exhibit altered immunostaining patterns in simian immunodeficiency virus encephalitis (SIVE). Here we show that E2F1 and the inactivated, hyperphosphorylated form of pRb (ppRb) also exhibit altered immunostaining patterns in human immunodeficiency virus encephalitis (HIVE). Quantification of E2F1 and ppRb staining by immunofluorescent confocal microscopy confirms a significant increase in E2F1 and ppRb in both HIVE and the simian model. This increase in E2F1 and ppRb staining correlates with an increase in the presence of activated macrophages, suggesting a link between changes in cell cycle proteins and the presence of activated macrophages. Changes in ppRb and E2F1 staining in SIVE also correlate with alterations in E2F/DNA binding complexes present in the nuclear and cytoplasmic fractions from both midfrontal cortex and basal ganglia. These findings suggest that changes in cell cycle proteins occur in both HIVE and the simian model and that these changes have functional implications for gene expression in neural cells under encephalitic conditions mediated by macrophage activation or infiltration.
4576.
Lim CC, Lee
KE, Lee WL, Tambyah PA, Lee CC, Sitoh YY, Auchus AP, Lin BK, Hui F Nipah
virus encephalitis: serial MR study of an emerging disease. Radiology. 2002
Jan;222(1):219-26.
PURPOSE: To
report the serial magnetic resonance (MR) imaging findings of the Nipah virus.
MATERIALS AND METHODS: Twelve patients underwent serial MR imaging. Eight
patients were examined at the outbreak; 11, at 1 month; and seven, at 6 months.
Contrast material-enhanced MR images, diffusion-weighted images, and
single-voxel proton MR spectroscopic images were reviewed. Clinical and
neurologic assessment, as well as analysis of the size, location, and
appearance of brain lesions on MR images, were performed. RESULTS: During the
outbreak, all eight patients had multiple small foci of high signal intensity
within the white matter on T2-weighted images. In six patients, cortical and
brain stem lesions were also detected, and five patients had diffusion-weighted
MR imaging-depicted hyperintensities. One month after the outbreak, five
patients had widespread tiny foci of high signal intensity on T1-weighted
images, particularly in the cerebral cortex. Diffusion-weighted images showed
decreased prominence or disappearance of lesions over time. There was no
evidence of progression or relapse of the lesions at 6-month follow-up. MR
spectroscopy depicted reduction in N-acetylaspartate-to-creatine ratio and
elevation of choline-to-creatine ratios. CONCLUSION: The Nipah virus has
findings unlike other viral encephalitides: small lesions that are primarily
within the white matter, with transient punctate cortical hyperintensities on
T1-weighted images.
4577.
Mankowski JL, Queen SE, Tarwater PM, Fox KJ, Perry VH.
Accumulation of beta-amyloid precursor protein in axons correlates with CNS
expression of SIV gp41. J Neuropathol Exp Neurol. 2002 Jan;61(1):85-90.
Axonal damage represented by accumulation of beta-amyloid precursor protein (beta-APP) develops in numerous central nervous system (CNS) diseases including human immunodeficiency virus (HIV) infection. To study the underlying mechanisms of axonal damage associated with HIV CNS infection, the amount of axonal beta-APP immunostaining in the corpus callosum of 24 simian immunodeficiency virus (SIV)-infected macaques and 3 control macaques was measured by computerized image analysis. The amounts of beta-APP accumulation were then compared with time post-inoculation, extent and character of CNS inflammation, and viral load in the CNS measured by the amount of immunohistochemical staining for the viral transmembrane protein gp41. Significant increases over control values were present in 10 of 24 SIV-infected animals. SIV encephalitis was present in 9 of the 10 animals with elevated beta-APP Increases in beta-APP correlated most strongly with levels of SIV gp41 in the brain (p = 0.005), but significant associations with macrophage infiltration and microglial activation (p = 0.04) and infiltration by cytotoxic lymphocytes (p = 0.05) also were identified. These data demonstrate that beta-APP accumulation in the white matter of SIV-infected macaques develops during SIV infection in close correlation with levels of viral replication and may serve as a sensitive marker of neuronal/axonal damage mediated by viral proteins.
4578.
Monath TP, Arroyo J, Levenbook I, Zhang ZX, Catalan J, Draper K,
Guirakhoo F. Single mutation in the flavivirus envelope protein hinge region
increases neurovirulence for mice and monkeys but decreases viscerotropism for
monkeys: relevance to development and safety testing of live, attenuated
vaccines. J Virol. 2002 Feb;76(4):1932-43.
A chimeric
yellow fever (YF) virus/Japanese encephalitis (JE) virus vaccine
(ChimeriVax-JE) was constructed by insertion of the prM-E genes from the
attenuated JE virus SA14-14-2 vaccine strain into a full-length cDNA clone of
YF 17D virus. Passage in fetal rhesus lung (FRhL) cells led to the emergence of
a small-plaque virus containing a single Met-->Lys amino acid mutation at
E279, reverting this residue from the SA14-14-2 to the wild-type amino acid. A
similar virus was also constructed by site-directed mutagenesis (J. Arroyo, F.
Guirakhoo, S. Fenner, Z.-X. Zhang, T. P. Monath, and T. J. Chambers, J. Virol.
75:934-942, 2001). The E279 mutation is located in a beta-sheet in the hinge
region of the E protein that is responsible for a pH-dependent conformational
change during virus penetration from the endosome into the cytoplasm of the
infected cell. In independent transfection-passage studies with FRhL or Vero
cells, mutations appeared most frequently in hinge 4 (bounded by amino acids
E266 to E284), reflecting genomic instability in this functionally important
region. The E279 reversion caused a significant increase in neurovirulence as
determined by the 50% lethal dose and survival distribution in suckling mice
and by histopathology in rhesus monkeys. Based on sensitivity and comparability
of results with those for monkeys, the suckling mouse is an appropriate host
for safety testing of flavivirus vaccine candidates for neurotropism. After
intracerebral inoculation, the E279 Lys virus was restricted with respect to
extraneural replication in monkeys, as viremia and antibody levels (markers of
viscerotropism) were significantly reduced compared to those for the E279 Met
virus. These results are consistent with the observation that empirically
derived vaccines developed by mouse brain passage of dengue and YF viruses have
increased neurovirulence for mice but reduced viscerotropism for humans.
4579.
Nau R, Bruck W. Neuronal injury in bacterial meningitis:
mechanisms and implications for therapy. Trends Neurosci. 2002 Jan;25(1):38-45.
Review.
In bacterial meningitis, long-term neurological sequelae and death are caused jointly by several factors: (1) the systemic inflammatory response of the host, leading to leukocyte extravasation into the subarachnoid space, vasculitis, brain edema and secondary ischemia; (2) stimulation of resident microglia within the CNS by bacterial compounds; and (3) possible direct toxicity of bacterial compounds on neurons. Neuronal injury is mediated by the release of reactive oxygen intermediates, proteases, cytokines and excitatory amino acids, and is executed by the activation of transcription factors, caspases and other proteases. In experimental meningitis, dexamethasone as an adjunct to antibiotic treatment leads to an aggravation of neuronal damage in the hippocampal formation, suggesting that corticosteroids might not be the ideal adjunctive therapy. Several approaches that interfere selectively with the mechanisms of neuronal injury are effective in animal models, including the use of nonbacteriolytic protein synthesis-inhibiting antibiotics, antioxidants and inhibitors of transcription factors, matrix metalloproteinases, and caspases.
4580.
Perez C, Montes M. Cutaneous leukocytoclastic vasculitis and
encephalitis associated with Myccoplasma pneumoniae infection Arch Intern Med.
2002 Feb 11;162(3):352-4. No abstract.
4581.
Portela LV, Brenol JC, Walz R, Bianchin M, Tort AB, Canabarro
UP, Beheregaray S, Marasca JA, Xavier RM, Neto EC, Goncalves CA, Souza DO. Serum S100B levels in patients with lupus
erythematosus: preliminary observation. Clin Diagn Lab Immunol. 2002
Jan;9(1):164-6.
S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age- and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.
4582.
Shenoy S, Wilson G, Prashanth HV, Vidyalakshmi K, Dhanashree B,
Bharath R. Primary meningoencephalitis
by Naegleria fowleri: first reported case from Mangalore, South India. J Clin
Microbiol. 2002 Jan;40(1):309-10.
A fatal case of primary amebic meningoencephalitis (PAM) in a 5-month-old infant is described. The disease may have been contracted during bathing. The source of water was from an artificial well. The clinical presentation, the isolation of the ameba from the cerebrospinal fluid, the poor response to amphotericin B, and the ultimate fatal outcome are all consistent with the diagnosis of PAM. On the basis of its ability to grow at temperatures above 30 degrees C, the morphology of the trophozoite, and the presence of flagellate forms, the ameba was identified as Naegleria fowleri. Pathogenic N. fowleri amebae were recovered from samples of water from the well. To our knowledge this case represents the second case of PAM in an infant in the absence of the history of swimming.
4583.
Skiest DJ. Focal neurological disease in patients with acquired
immunodeficiency syndrome. Clin Infect Dis. 2002 Jan 1;34(1):103-15. Review.
Focal neurological disease in patients with acquired immunodeficiency syndrome may be caused by various opportunistic pathogens and malignancies, including Toxoplasma gondii, progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV), and Epstein-Barr virus-related primary central nervous system (CNS) lymphoma. Diagnosis may be difficult, because the findings of lumbar puncture, computed tomography (CT), and magnetic resonance imaging are relatively nonspecific. Newer techniques have led to improved diagnostic accuracy of these conditions. Polymerase chain reaction (PCR) of cerebrospinal fluid specimens is useful for diagnosis of PML, CNS lymphoma, and CMV encephalitis. Recent studies have indicated the diagnostic utility of new neuroimaging techniques, such as single-photon emission CT and positron emission tomography. The combination of PCR and neuroimaging techniques may obviate the need for brain biopsy in selected cases. However, stereotactic brain biopsy, which is associated with relatively low morbidity rates, remains the reference standard for diagnosis. Highly active antiretroviral therapy has improved the prognosis of several focal CNS processes, most notably toxoplasmosis, PML, and CMV encephalitis.
4584.
Straumanis JP, Tapia MD, King JC. Influenza B infection associated
with encephalitis: treatment with oseltamivir. Pediatr Infect Dis J. 2002
Feb;21(2):173-5.
Encephalitis associated with acute influenza infection is unusual in nonepidemic years. A case of a 10-year-old child with influenza B encephalitis and profound weakness who was treated with oseltamivir is presented. This case illustrates several of the unusual findings associated with influenza infections and the result of treatment of influenza B encephalitis with oseltamivir.
4585.
Wallington T, Weir E. Varicella control and vaccine coverage:
issues and challenges. CMAJ. 2002 Mar 5;166(5):631-2. No abstract.
4586.
Whitley RJ, Gnann JW. Viral encephalitis: familiar infections
and emerging pathogens. Lancet. 2002 Feb 9;359(9305):507-13. Review.
Significant advances have been made in our understanding of the natural history and pathogenesis of viral encephalitides. The development of PCR has greatly increased our ability to diagnose viral infections of the central nervous system, particularly for herpes and enteroviral infections. Advancing knowledge has led to the recognition that some encephalitides can be reliably prevented by vaccination (eg, Japanese encephalitis and rabies). For other pathogens such as the arboviruses, the focus has been on prevention by vector control. Finally, effective therapy has been established for a very limited number of viral infections (eg, acyclovir for herpes simplex encephalitis). Other potentially useful treatments, such as pleconaril for enteroviral meningoencephalitis are under clinical evaluation. We review current understanding of viral encephalitides with particular reference to emerging viral infections and the availability of existing treatment regimens.
4587.
Wilcox RD. Cidofovir: progress in the treatment of progressive
multifocal encephalopathy (PML)? HIV Clin. 2002 Winter;14(1):1-2. No abstract.
4588.
Zeller V, Truffot C, Agher R, Bossi P, Tubiana R, Caumes E,
Jouan M, Bricaire F, Katlama C.
Discontinuation of secondary prophylaxis against disseminated
Mycobacterium avium complex infection and toxoplasmic encephalitis. Clin Infect
Dis. 2002 Mar 1;34(5):662-7.
We retrospectively studied outcomes for patients infected with human
immunodeficiency virus who received highly active antiretroviral therapy (HAART) and had stopped receiving secondary prophylaxis against toxoplasmic encephalitis (TE) or disseminated Mycobacterium avium complex (MAC) infection. Nineteen patients had a history of TE, and 26 had a history of disseminated MAC infection. The median duration of secondary prophylaxis was 27 months, and the median duration of HAART before discontinuation of secondary prophylaxis was 22 months. Median CD4(+) cell counts at the time of cessation of secondary prophylaxis against TE or disseminated MAC infection were 404 and 105 cells/mm(3), respectively. Plasma virus load was undetectable in 68% of the patients who had a history of TE and in 31% of patients who had a history of disseminated MAC infection. Patients were followed up for a median of 29 months after discontinuation of secondary prophylaxis; no relapses occurred in patients with a history of TE, and 3 relapses occurred in patients with a history of disseminated MAC infection (incidence, 4 relapses per 100 person-years).
4589.
Zerr DM, Gupta D, Huang ML, Carter R, Corey L. Effect of antivirals
on human herpesvirus 6 replication in hematopoietic stem cell transplant
recipients. Clin Infect Dis. 2002 Feb 1;34(3):309-17.
Human herpesvirus 6 (HHV-6) appears to cause central nervous system (CNS) syndromes, especially in hematopoietic stem cell transplant (HSCT) recipients. We reviewed our experience with HHV-6-associated CNS disease to evaluate both the clinical and virological presentation and response to antiviral therapy. A search of our virology database from January 1998 through June 2000 identified 11 HSCT recipients who had HHV-6 DNA detected by polymerase chain reaction in cerebrospinal fluid (CSF); 8 of whom had CNS dysfunction without another clear etiology identified. HHV-6 levels in serum and CSF were evaluated before and after ganciclovir and/or foscarnet therapy. Median log HHV-6 CSF levels appeared to decrease over time concurrent with antiviral therapy (serum level, 2.0 vs. 0 copies/mL [P=.38]; CSF level, 4.4 vs. 2.0 copies/mL [P=.13], sign test). Our data suggests that HHV-6 may cause moderate to severe CNS disease after HSC transplantation. Prospective studies are needed to define the spectrum of HHV-6-associated disease and to determine whether antiviral therapy offers clinical benefit.
4590.
Ziegner UH, Kobayashi RH, Cunningham-Rundles C, Espanol T, Fasth
A, Huttenlocher A, Krogstad P, Marthinsen L, Notarangelo LD, Pasic S, Rieger
CH, Rudge P, Sankar R, Shigeoka AO, Stiehm ER, Sullivan KE, Webster AD, Ochs
HD. Progressive neurodegeneration in
patients with primary immunodeficiency disease on IVIG treatment. Clin Immunol.
2002 Jan;102(1):19-24.
We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended. (c)2001 Elsevier Science.
5277.
Antunes NL,
Souweidane MM, Lis E, Rosenblum MK, Steinherz PG. Methotrexate leukoencephalopathy
presenting as Kluver-Bucy syndrome and uncinate seizures. Pediatr Neurol. 2002
Apr;26(4):305-8.
Methotrexate causes several biochemical
changes that impact the nervous system. The neurotoxicity usually affects the
cerebral white matter, causing a leukoencephalopathy that can be chronic and
progressive with cognitive decline. A 15-year-old male developed olfactory
seizures and behavioral abnormalities (hypersexuality, placidity, and memory
disturbances) compatible with partial Kluver-Bucy syndrome after treatment for
central nervous system leukemia with intraventricular methotrexate. A magnetic
resonance imaging study revealed evidence of white matter disease affecting
both temporal lobes. A brain biopsy revealed a necrotizing encephalopathy
compatible with methotrexate-related white matter injury. It may be prudent to
verify normal cerebrospinal fluid dynamics before the administration of
intraventricular methotrexate in children with a history of central nervous
system leukemia.
5278.
Bauer J, Bien
CG, Lassmann H. Rasmussen's encephalitis: a role for autoimmune cytotoxic T
lymphocytes. Curr Opin Neurol. 2002 Apr;15(2):197-200. Review.
The present review describes advances in
Rasmussen's encephalitis (also known as Rasmussen's syndrome), an unihemispheric
intractable epileptic disease with persistent inflammation. Specific attention
is given to the recent recognition of cytotoxicity by CD8+/granzyme-B-positive
T lymphocytes as a new pathogenic mechanism of neuronal damage.
5279.
Beaman MH,
Wesselingh SL. 4: Acute community-acquired meningitis and encephalitis. Med J
Aust. 2002 Apr 15;176(8):389-96. Review.
Acute meningitis and encephalitis are
medical emergencies that require prompt assessment (usually by cerebral imaging
and lumbar puncture) and treatment; specialist consultation is recommended. In
acute meningitis, early administration of antibiotics can be life-saving
(usually high-dose penicillin and/or a third-generation cephalosporin);
antibiotics may be needed before referral to hospital. Emergence of penicillin
and cephalosporin resistance in Streptococcus pneumoniae has necessitated more
complex antibiotic regimens that include vancomycin or rifampicin for empirical
treatment of meningitis. Adjunctive dexamethasone therapy may be of benefit in
children with Haemophilus influenzae meningitis; there is no controlled
evidence of its benefit in adults, but it could be considered in those with
raised intracranial pressure. In possible encephalitis, empirical therapy with
intravenous aciclovir should be given to cover herpes simplex virus (HSV) until
the cause is established; HSV encephalitis may be fatal and leaves up to 50% of
survivors with long-term sequelae.
5280.
Beschorner R,
Schluesener HJ, Gozalan F, Meyermann R, Schwab JM. Infiltrating CD14+ monocytes
and expression of CD14 by activated parenchymal microglia/macrophages
contribute to the pool of CD14+ cells in ischemic brain lesions. J
Neuroimmunol. 2002 May;126(1-2):107-15.
CD14, a key pattern recognition receptor of
the innate immune system, is a surface molecule on monocytic cells involved in
cellular activation. We investigated 18 autopsy cases of focal cerebral
infarctions (FCI) by immunohistochemistry to examine CD14 expression following
ischemia. Controls confirmed constitutive CD14 expression by few perivascular
cells. In contrast to quiescent CD14- parenchymal microglial cells, following
ischemia activated microglia/macrophages expressed abundant CD14. In FCI, CD14+
cells increased both in perivascular spaces and in brain parenchyma within 1-2.5
days and remained elevated until late stages. Early CD14 expression suggests an
essential part of CD14 in the acute inflammatory response following stroke.
5281.
Chan PK, Chik
KW, To KF, Li CK, Shing MM, Ng KC, Yuen PM, Cheng AF. Case report: human
herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell
transplant recipient. J Med Virol. 2002 Apr;66(4):493-6.
Previous studies have suggested a
neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV-7). In
this report, a case of fatal encephalitis is described and its association with
HHV-7 infection is discussed. An 8-year-old girl received a peripheral blood
stem cell transplant for relapsed acute lymphoblastic leukaemia. The
post-transplant period was uneventful and a course of intrathecal chemotherapy
was given on Day-30. On Day-41, she developed acute encephalopathy with
diplopia and nystagmus. She ran a rapid downhill course and succumbed despite
antiviral treatment. The only positive pathological finding was the multiple
microscopic foci of haemorrhage associated with neuronal degeneration detected
in the brain stem. All microbiological investigations were negative, except for
the presence of HHV-7 DNA in cerebrospinal fluid and brain stem tissue samples.
Copyright 2002 Wiley-Liss, Inc.
5282.
Dunlop O,
Bjorklund R, Bruun JN, Evensen R, Goplen AK, Liestol K, Sannes M, Maehlen J,
Myrvang B. Early psychomotor slowing predicts the development of HIV dementia
and autopsy-verified HIV encephalitis. Acta Neurol Scand. 2002 Apr;105(4):270-5.
OBJECTIVES- To ask if slowed motor speed
predicts later human immunodeficiency virus (HIV) dementia and HIV
encephalitis. METHODS- In 100 deceased acquired immunodeficiency syndrome
(AIDS) patients prior results from repeated testing of the movement reaction
time test were correlated with later clinical signs of HIV dementia and with
neuropathological signs of HIV encephalitis. Autopsy was performed in 72
patients. RESULTS- Movement reaction time 1-2 years prior to death, or at the
time of clinical AIDS diagnosis predicted both development of HIV dementia
(P<0.05) and HIV encephalitis at autopsy (P<0.01). CONCLUSION- Testing
for early psychomotor slowing may be used to identify patients at risk of HIV
dementia and HIV encephalitis.
5283.
Fontoura P, Vale
J, Lima C, Scaravilli F, Guimaraes J. Progressive myoclonic ataxia and JC virus
encephalitis in an AIDS patient. J Neurol Neurosurg Psychiatry. 2002
May;72(5):653-6.
A case of progressive myoclonic ataxia in
an AIDS patient is described, which evolved over a 13 month period. The ataxia
persisted as the only clinical finding for several months before the appearance
of a severe tetraparesis and cachexia. Throughout the clinical progression,
magnetic resonance imaging (MRI) revealed the presence of bilateral,
progressive, isolated, and symmetrical lesions involving the red nuclei,
subthalami, thalami, lenticular nuclei, and primary motor cortices.
Neuropathological examination, supplemented by in situ hybridisation for JC
virus DNA, confirmed that the lesions were those of progressive multifocal
leucoencephalopathy (PML). The exceptional clinical presentation of PML in this
case is the first report of progressive myoclonic ataxia caused by PML. The
selective nature of the lesions confirms the role of the
dentato-rubral-thalamo-cortical tract in the pathogenesis of progressive
myoclonic ataxia. The atypical MRI findings further emphasise the need for
expanded diagnostic criteria for PML in AIDS patients and support the use of
more aggressive diagnostic methods as new treatments become available.
5284.
Gerber JE,
Johnson JE, Scott MA, Madhusudhan KT. Fatal meningitis and encephalitis due to
Bartonella henselae bacteria. J Forensic Sci. 2002 May;47(3):640-4.
Bacterial infection due to Bartonella
henselae commonly develops in children and young adults following cat/dog
contacts and/or cat/dog scratches. Regional lymphadenopathy is its most common
clinical expression. However, encephalitis and Parinaud's syndrome
(oculoglandular syndrome) have also been reported as has systemic illness. A
review of the international literature in all languages revealed no fatal
complications in immunocompetent hosts. A four-year-old white child with no
underlying illness began to have seizure-like activity. She was taken to a
local hospital and subsequently transferred to a medical center. The child was
treated aggressively for seizures and fever of unknown origin. However, her
condition rapidly declined and she died without a specific diagnosis. At
autopsy there was marked cerebral edema with no gross evidence of acute
meningitis. Microscopic exams revealed multiple granulomatous lesions as well
as a meningitis and encephalitis. A variety of cultures and stains were
negative for acid fast and fungal organisms. Warthin-Starry stains of involved
tissue including brain and liver revealed pleomorphic rod shaped bacilli
consistent with Barronella henselae. Analysis of brain tissue with polymerase
chain reaction (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was
definitive for DNA of Bartonella henselae bacteria.
5285.
Gibbs AN,
Moroney J, Foley-Nolan D, O'Connell PG. Neuromyelitis optica (Devic's syndrome)
in systemic lupus erythematosus: a case report. Rheumatology (Oxford). 2002
Apr;41(4):470-1. No abstract.
5286.
Gorry PR,
Taylor J, Holm GH, Mehle A, Morgan T, Cayabyab M, Farzan M, Wang H, Bell JE,
Kunstman K, Moore JP, Wolinsky SM, Gabuzda D. Increased CCR5 affinity and
reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency
virus type 1 isolate. J Virol. 2002 Jun;76(12):6277-92.
Most human immunodeficiency virus type 1
(HIV-1) viruses in the brain use CCR5 as the principal coreceptor for entry
into a cell. However, additional phenotypic characteristics are necessary for
HIV-1 neurotropism. Furthermore, neurotropic strains are not necessarily
neurovirulent. To better understand the determinants of HIV-1 neurovirulence,
we isolated viruses from brain tissue samples from three AIDS patients with
dementia and HIV-1 encephalitis and analyzed their ability to induce syncytia
in monocyte-derived macrophages (MDM) and neuronal apoptosis in primary brain
cultures. Two R5X4 viruses (MACS1-br and MACS1-spln) were highly fusogenic in
MDM and induced neuronal apoptosis. The R5 viruses UK1-br and MACS2-br are both
neurotropic. However, only UK1-br induced high levels of fusion in MDM and
neuronal apoptosis. Full-length Env clones from UK1-br required lower CCR5 and
CD4 levels than Env clones from MACS2-br to function efficiently in
cell-to-cell fusion and single-round infection assays. UK1-br Envs also had a
greater affinity for CCR5 than MACS2-br Envs in binding assays. Relatively high
levels of UK1-br and MACS2-br Envs bound to CCR5 in the absence of soluble CD4.
However, these Envs could not mediate CD4-independent infection, and MACS2-br
Envs were unable to mediate fusion or infection in cells expressing low levels
of CD4. The UK1-br virus was more resistant than MACS2-br to inhibition by the
CCR5-targeted inhibitors TAK-779 and Sch-C. UK1-br was more sensitive than
MACS2-br to neutralization by monoclonal antibodies (2F5 and immunoglobulin
G1b12 [IgG1b12]) and CD4-IgG2. These results predict the presence of HIV-1
variants with increased CCR5 affinity and reduced dependence on CCR5 and CD4 in
the brains of some AIDS patients with central nervous system disease and
suggest that R5 variants with increased CCR5 affinity may represent a
pathogenic viral phenotype contributing to the neurodegenerative manifestations
of AIDS.
5287.
Karim A,
Ahmed S, Rossoff LJ. Legionnaire's disease associated with acute encephalitis
and arrhythmia. Crit Care Med. 2002 May;30(5):1028-9.
OBJECTIVE: To report an unusual,
life-threatening combination of neurologic, cardiac, and gastrointestinal
symptoms in the presence of a community-acquired pneumonia. DESIGN: Case
report. SETTING: University hospital. PATIENT: Previously healthy young male.
INTERVENTION: Diagnostic fiberoptic bronchoscopy, lumber puncture, magnetic
resonance imaging of the brain, and institution of systemic antibiotics. MAIN
RESULT: Gradual clinical improvement of a multiple-system illness. CONCLUSION:
Legionellosis should be considered in the differential diagnosis of patients
presenting with neurologic, cardiac, and gastrointestinal symptoms,
particularly in the presence of radiographic pneumonia. Furthermore, Legionella
meningoencephalitis may present with findings on magnetic resonance imaging
previously thought to be characteristic of herpes encephalitis.
5289.
Kastrukoff
LF, Kim SU. Oligodendrocytes from human donors differ in resistance to herpes
simplex virus 1 (HSV-1). Glia. 2002 Apr 1;38(1):87-92.
Primary cultures of human oligodendrocytes
(HOLs) were established from six different donors. Differences in resistance to
infection with herpes simplex virus 1 (HSV-1) were determined between the primary
cultures of HOL in tissue culture infective dose 50 (TCID(50)), indirect
immunofluoresence (IF), and serial electron microscopy (EM) studies. Virus
production at different multiplicities of infection (MOIs) indicated that
differences in HSV-1 replication were statistically significant and
MOI-dependent. Overall, virus yield from the HOL cultures infected at an MOI of
1 increased up to 6 days postinfection (PI); no additional enhancement occurred
at 7 days PI. However, differences in the replication capacity of the six HOL
cultures observed at 5 days PI persisted at 6 and 7 days PI. When taken
together, the results of these investigations indicate that, similar to
experimental animals, resistance to HSV-1 differs between primary cultures of
HOL and is donor-dependent. The results also raise the possibility that similar
to experimental animals, resistance to HSV-1, mediated at the level of HOL, may
be genetically determined. Furthermore, permissive infections of primary
cultures of HOL were established with HSV-1 over a wide range of MOIs, similar
to results obtained with viral infection of primary murine oligodendrocytes,
but neither latent nor abortive infections of HOL were induced in vitro, even
at very low MOIs. Resistance to HSV-1, mediated by glial cells, is a nonimmune
mechanism that may influence the development of acute CNS infection in man as
well as individual susceptibility to this virus. Copyright 2002 Wiley-Liss,
Inc.
5290.
Lee JH, Na
DG, Choi KH, Kim KJ, Ryoo JW, Lee SY, Suh YL. Subcortical low intensity on MR
images of meningitis, viral encephalitis, and leptomeningeal metastasis. AJNR
Am J Neuroradiol. 2002 Apr;23(4):535-42.
BACKGROUND AND PURPOSE: Subcortical
low-intensity lesion on T2-weighted images is an uncommon manifestation of
ischemia, multiple sclerosis, and Sturge-Weber disease. This study was
performed to determine whether subcortical low signal intensity is an MR
feature of meningitis, viral encephalitis, or leptomeningeal metastasis and to
investigate a cause of subcortical low intensity. METHODS: We retrospectively
reviewed MR images of 117 patients with meningitis, encephalitis (viral or
unknown), or leptomeningeal metastasis for the presence of subcortical low
intensity, meningeal enhancement, signal intensity change of cortex, and change
in subcortical low intensity on follow-up images. Diffusion-weighted (DW)
images and apparent diffusion coefficient (ADC) maps were obtained in 55
patients. Subcortical low-intensity lesions were also quantitatively analyzed
on T2-weighted, fluid-attenuated inversion recovery (FLAIR), and DW images.
RESULTS: Subcortical low intensity was found in nine (23.7%) of 38 patients
with encephalitis (viral, 31; unknown origin, 7), five (24%) of 21 with
leptomeningeal metastasis, and five (9%) of 58 with meningitis. Leptomeningeal
enhancement was observed in 100% and cortical hyperintensity in 14 (74%) of 19
patients with subcortical low intensity. Leptomeningeal enhancement was seen in
46 (47%) and cortical hyperintensity in 33 (34%) of 98 patients without subcortical
low intensity. Subcortical low intensity disappeared or decreased in extent on
follow-up MR images in all seven patients who underwent follow-up. ADC of
subcortical low-intensity lesions was lower than that of the contralateral area
and decreased by 9.3 +/- 11.4%. CONCLUSION: Subcortical low intensity was
uncommonly found in meningitis, viral encephalitis, and leptomeningeal
metastasis. It is a nonspecific MR sign of various meningeal and cortical
diseases. Although the cause of subcortical low intensity remains uncertain,
free radical formation may play a role as a causative factor.
5291.
MacLean HJ,
Douen AG. Severe amnesia associated with human herpesvirus 6 encephalitis after
bone marrow transplantation. Transplantation. 2002 Apr 15;73(7):1086-9.
BACKGROUND: Human herpesvirus 6 (HHV-6)
appears to have a predilection for immunocompromised patients and has been
implicated as a cause of posttransplant encephalitis. However, the pathogenesis,
as well as the appropriate means of diagnosis and treatment of HHV-6
encephalitis is unclear. METHOD: We describe a case of a 20-year-old male
university student with anemia who presented with an acute, severe amnesia 1
month after bone marrow transplantation. His illness was subsequently
attributed to HHV-6 encephalitis. RESULTS: Cerebrospinal fluid analysis was
consistent with encephalitis and polymerase chain reaction confirmed the
presence of HHV-6 DNA in both cerebrospinal fluid and serum. No other herpes
virus particles were detected. MRI showed bilateral hippocampal involvement.
Treatment with acyclovir resulted in a decrease in serum HHV-6 DNA to
undetectable levels, coincident with improvement of both memory and lesions on
MRI. CONCLUSIONS: This case provides strong clinical and radiological evidence
of the reversibility of this disease process and supports the recommendations
for empiric treatment of post transplant patients with laboratory evidence of
HHV-6 infection, culture or polymerase chain reaction, plus clinical symptoms
compatible with HHV-6 infection.
5292.
Misra UK,
Kalita J. Prognosis of Japanese encephalitis patients with dystonia compared to
those with parkinsonian features only. Postgrad Med J. 2002 Apr;78(918):238-41.
OBJECTIVES: A number of movement disorders
have been reported in Japanese encephalitis (JE). The prognostic significance
of these movement disorders, however, has not been evaluated. The present study
reports the prognostic significance of parkinsonian features and dystonia in
JE. PATIENTS AND METHODS: During 1992 and 1998, 50 JE patients were managed; 35
of them developed movement disorders (the study group). The diagnosis of JE was
based on clinical, radiological, and serological criteria. Parkinsonian features
were rated by the unified Parkinson's disease rating scale and dystonia by the
dystonia rating scale. The patients with parkinsonian features only were
classified into group I and those with additional dystonia or dyskinesia into
group II. The outcome was defined at the end of three months into poor,
partial, and complete recovery depending on how the patients coped with daily
living activities. RESULTS: The patients' ages ranged from 2 to 64 years and 11
were females. The admission mean Glasgow coma scale score was 6.9 (range 4-13).
The movement disorders were noted after 1-4 weeks of ictus. There were 16
patients in group I and 19 in group II. The parkinsonian features were more
pronounced in group II than in group I. At three months of follow up, fewer patients
had parkinsonian features in group I than group II. Hypophonia, however,
persisted in 12 patients in group I and 16 in group II until the three month
follow up. In group II, the mean dystonia score was 3.2 which regressed to 1.8
at three months. Tremor was present in five patients in groups I and eight in
group II. Cranial computed tomography was abnormal in six and magnetic
resonance imaging abnormal in 15 patients in group I and in nine and 12
patients respectively in group II. The thalamus was most frequently involved
(11 patients in each group), basal ganglia (four in group I and six in group
II), and midbrain (six in group I and one in group II). Group II patients had
poorer recovery compared with group I. In group I, at the end of three months functional
recovery was complete in 10, partial in two, and poor in three patients. In
group II, four patients had complete, seven partial, and eight poor recovery.
CONCLUSION: JE results in a transient form of parkinsonian syndrome, which is
associated with a lower frequency of tremor and prominent hypophonia. The
presence of dystonia suggests more severe illness and poorer prognosis.
5293.
Redington JJ,
Tyler KL. Viral infections of the nervous system, 2002: update on diagnosis and
treatment. Arch Neurol. 2002 May;59(5):712-8. Review. No abstract.
5294.
Saha M, Kumar
S, Das A, Gupta RK. Similarities and differences of MR findings between
Japanese encephalitis and Wilson's disease. Eur Radiol. 2002 Apr;12(4):872-6.
Although Japanese Encephalitis (JE) and
Wilson's disease (WD) are different entities, MR findings in both these
conditions are quite similar. The purpose of this retrospective study was to
find out the similarities and differences between JE and WD on MR imaging. The
study group comprised 25 proven cases of JE and 10 cases of WD. Spin echo (SE)
TI- and T2-weighted imaging was performed on a 1.5-T MR system. Fourteen of
these 35 cases (10 JE, 4 WD) were also examined using T1-weighted magnetization
transfer (MT) SE sequence before and after contrast administration. Although
both JE and WD showed similar topographical distribution of lesions,
predominant involvement of the basal ganglia and thalami, there were some
differences. Brain stem lesion was more frequent for WD than for JE, and
posteromedial part of the thalami was spared in WD. The lesion characteristics
were also different between both; in WD mixed intensity in the basal ganglia
and hyperintense linear rim at the peripheral putamen was observed frequently,
whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage
in the thalami and meningeal enhancement were seen only in the patients with
JE. These characteristic lesion criteria may help in differentiation of JE from
WD on MR imaging.
5295.
Sethi S,
Bhargava SC. Kleine-Levin syndrome following acute non-specific encephalitis.
Indian J Pediatr. 2002 May;69(5):451. No abstract.
5296.
Shimizu T,
Matsuishi T, Iwamoto R, Handa K, Yoshioka H, Kato H, Ueda S, Hara H, Tabira T,
Mekada E. Elevated levels of anti-CD9 antibodies in the cerebrospinal fluid of
patients with subacute sclerosing panencephalitis. J Infect Dis. 2002 May
1;185(9):1346-50.
Subacute sclerosing panencephalitis (SSPE)
is a slowly progressive and highly lethal disease of the central nervous
system. Although the primary cause of SSPE is believed to be persistent
infection of neuron and glial cells by a measles virus, the precise mechanism
of the progression of this disease has not yet been elucidated. CD9, a member
of the tetraspanin family, is expressed in myelin and other nervous tissues.
This study detected significant amounts of anti-CD9 antibodies in the
cerebrospinal fluid (CSF) of all patients with SSPE included in the study.
Anti-CD9 antibodies were also detected in the CSF of some patients with other
neurologic disorders, but those patients had lower levels of anti-CD9
antibodies than did the patients with SSPE. The level of anti-CD9 antibodies
was elevated and reached a peak that coincided with the appearance of brain
atrophy. These findings shed light on a new aspect of the causes and
progression of SSPE.
5297.
Stone R.
Infectious disease. Siberia's deadly stalker emerges from the shadows. Science.
2002 Apr 26;296(5568):642-5. No
abstract.
5298.
Warrilow D,
Northill JA, Pyke A, Smith GA. Single rapid TaqMan fluorogenic probe based PCR
assay that detects all four dengue serotypes. J Med Virol. 2002
Apr;66(4):524-8.
Public health laboratories require rapid
diagnosis of dengue outbreaks for application of measures such as vector
control. We have developed a rapid single fluorogenic probe-based polymerase
chain reaction assay for the detection of all four dengue serotypes
(FUDRT-PCR). The method employs primers and probe that are complementary to the
evolutionarily conserved 3' untranslated region of the dengue genome. The assay
detected viral RNA of strains of all four dengue serotypes but not of the
flaviviruses Japanese encephalitis virus, Murray Valley encephalitis virus,
Kunjin, Stratford, West Nile, Alfuy or Yellow fever. When compared to an
existing nested-PCR assay for the detection of dengue on clinical samples,
FUDRT-PCR detected dengue 1 (100%, n=14), dengue 2 (85%, n=13), dengue 3 (64%,
n=14) and dengue 4 (100%, n=3) with the indicated sensitivities. FUDRT-PCR
enables diagnosis of acute dengue infection in four hours from sample receipt.
In addition, a single-test procedure should result in a reduction in the number
of tests performed with considerable cost savings for diagnostic laboratories.
Copyright 2002 Wiley-Liss, Inc.
5299.
Weil AA,
Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex
encephalitis: rethinking an initial negative polymerase chain reaction result.
Clin Infect Dis. 2002 Apr 15;34(8):1154-7.
A statewide encephalitis diagnostic project
of the California State Department of Health Services found that herpes simplex
virus 1 DNA may not be detectable by molecular methods early in the clinical
course of herpes simplex encephalitis.
Pathogenesis :
5300.
Inoue T, Kira
R, Nakao F, Ihara K, Bassuny WM, Kusuhara K, Nihei K, Takeshita K, Hara T. Contribution of the interleukin 4 gene to
susceptibility to subacute sclerosing panencephalitis. Arch Neurol. 2002
May;59(5):822-7.
BACKGROUND: Although the exact pathogenesis
of subacute sclerosing panencephalitis (SSPE) remains to be determined, both viral
and host factors seem to be involved. OBJECTIVE: To identify host genetic
factors involved in the development of SSPE. METHODS: We investigated the
association of polymorphisms in the T helper (Th)1 and Th2 cytokine, and
related genes (interferon [IFN]-gamma, IFN-gamma receptor 1 [IFN-gamma R1],
IFN-gammaR2 [IRF-1], interleukin 12 receptor beta 1 [IL-12Rbeta1], IL-4, IL-4R,
and IL-10 genes) with SSPE in Japanese subjects. RESULTS: A significant
association (P =.03) was observed between SSPE and the T allele of the
biallelic polymorphism at position -589 in the promoter region of the IL-4
gene. The IRF-1 allele 1 tended to interact with the IL-4 promoter -589 T
genotype in the development of SSPE (P =.06), as judged on logistic regression
analysis. The frequency of the genotype combination of IL-4 promoter -589 T and
IRF-1 allele 1 (at least 1 allele) in patients with SSPE was much higher than
that in the controls (47.7% vs 22.0%; P =.003, chi2 analysis). However, there
was no association between other polymorphisms and SSPE. CONCLUSION: To our
knowledge, this study is the first to demonstrate the possibility that the IL-4
promoter gene -589 T gene polymorphism with increased IL-4 synthesis in
combination with IRF-1 allele 1 confers host genetic susceptibility to SSPE in
Japanese subjects.
5301.
Lee E, Lobigs
M. Mechanism of virulence attenuation of glycosaminoglycan-binding variants of
Japanese encephalitis virus and Murray Valley encephalitis virus. J Virol. 2002
May;76(10):4901-11.
The in vivo mechanism for virulence
attenuation of laboratory-derived variants of two flaviviruses in the Japanese
encephalitis virus (JEV) serocomplex is described. Host cell adaptation of JEV
and Murray Valley encephalitis virus (MVE) by serial passage in adenocarcinoma
cells selected for variants characterized by (i) a small plaque phenotype, (ii)
increased affinity to heparin-Sepharose, (iii) enhanced susceptibility to
inhibition of infectivity by heparin, and (iv) loss of neuroinvasiveness in a
mouse model for flaviviral encephalitis. We previously suggested that virulence
attenuation of the host cell-adapted variants of MVE is a consequence of their
increased dependence on cell surface glycosaminoglycans (GAGs) for attachment
and entry (E. Lee and M. Lobigs, J. Virol. 74:8867-8875, 2000). In support of
this proposition, we find that GAG-binding variants of JEV and MVE were rapidly
removed from the bloodstream and failed to spread from extraneural sites of
replication into the brain. Thus, the enhanced affinity of the attenuated variants
for GAGs ubiquitously present on cells and extracellular matrices most likely
prevented viremia of sufficient magnitude and/or duration required for virus
entry into the brain parenchyma. This mechanism may also account, in part, for
the attenuation of the JEV SA14-14-2 vaccine, given the sensitivity of the
virus to heparin inhibition. A pronounced loss of the capacity of the
GAG-binding variants to produce disease was also noted in mice defective in the
alpha/beta interferon response, a mouse strain shown here to be highly
susceptible to infection with JEV serocomplex flaviviruses. Despite the close
genetic relatedness of JEV and MVE, the variants selected for the two viruses
were altered at different residues in the envelope (E) protein, viz., Glu(306)
and Asp(390) for JEV and MVE, respectively. In both cases the substitutions
gave the protein an increased net positive charge. The close spatial proximity
of amino acids 306 and 390 in the predicted E protein structure strongly
suggests that the two residues define a receptor-binding domain involved in
virus attachment to sulfated proteoglycans.
5302.
Lin TY, Chang
LY, Hsia SH, Huang YC, Chiu CH, Hsueh C, Shih SR, Liu CC, Wu MH. The 1998
enterovirus 71 outbreak in Taiwan: pathogenesis and management. Clin Infect
Dis. 2002 May 1;34 Suppl 2:S52-7.
The most recently discovered enterovirus,
enterovirus 71 (EV71), is neurotropic and may cause severe disease and sudden
death in children. In 1998, a large outbreak of enterovirus infection occurred
in Taiwan that resulted in 405 severe cases in children and 78 deaths. Of the
78 children who died, 71 (91%) were <5 years old. EV71 was the primary agent
in fatal cases of infection. Most of these patients died within 1-2 days of
admission to the hospital. We hypothesize that EV71 directly attacks the
central nervous system and causes neurogenic pulmonary edema and cardiac
decompensation through the mechanism of sympathetic hyperactivity and
inflammatory responses. Early recognition of risk factors and intensive care are crucial to successful
treatment of this fulminant infection. After poliovirus is eradicated, EV71
will become the most important enterovirus that affects children, and
development of a vaccine may be the only effective measure against it.
5303.
Shi PY,
Tilgner M, Lo MK, Kent KA, Bernard KA. Infectious cDNA clone of the epidemic
west nile virus from New York City. J Virol. 2002 Jun;76(12):5847-56.
We report the first full-length infectious
clone of the current epidemic, lineage I, strain of West Nile virus (WNV). The
full-length cDNA was constructed from reverse transcription-PCR products of
viral RNA from an isolate collected during the year 2000 outbreak in New York
City. It was cloned into plasmid pBR322 under the control of a T7 promoter and
stably amplified in Escherichia coli HB101. RNA transcribed from the
full-length cDNA clone was highly infectious upon transfection into BHK-21
cells, resulting in progeny virus with titers of 1 x 10(9) to 5 x 10(9) PFU/ml.
The cDNA clone was engineered to contain three silent nucleotide changes to
create a StyI site (C to A and A to G at nucleotides [nt] 8859 and 8862,
respectively) and to knock out an EcoRI site (A to G at nt 8880). These genetic
markers were retained in the recovered progeny virus. Deletion of the 3'-terminal
199 nt of the cDNA transcript abolished the infectivity of the RNA. The plaque
morphology, in vitro growth characteristics in mammalian and insect cells, and
virulence in adult mice were indistinguishable for the parental and recombinant
viruses. The stable infectious cDNA clone of the epidemic lineage I strain will
provide a valuable experimental system to study the pathogenesis and
replication of WNV.
5304.
Sweet TM,
Valle LD, Khalili K. Molecular biology and immunoregulation of human
neurotropic JC virus in CNS. J Cell Physiol. 2002 Jun;191(3):249-56. Review.
The human polyomavirus, JC virus (JCV),
provides an excellent model system to investigate the reciprocal interaction of
the immune and nervous systems. Infection with JCV occurs during childhood and
the virus remains in the latent state with no apparent clinical symptoms.
However, under immunosuppressed conditions, the virus enters the lytic cycle
and upon cytolytic destruction of glial cells, causes the fatal demyelinating
disease of the central nervous system (CNS), named progressive multifocal
leukoencephalopathy (PML). In this short review, we discuss the molecular
pathogenesis of PML by highlighting the role of the immune system in modulating
JCV gene activation and replication, and the latency/reactivation of this virus
upon immunosuppression. Further, due to the higher incidence of PML among AIDS
patients, we further elaborate on the cross-talk between JCV and HIV-1 by
direct and indirect pathways that lead to enhanced expression of the JCV genome.
Copyright 2002 Wiley-Liss, Inc.
Vaccines:
5305.
Munch G,
Robinson SR. Alzheimer's vaccine: a cure as dangerous as the disease? J Neural
Transm 2002 Apr;109(4):537-9
Studies in transgenic mouse models of
Alzheimer's disease suggested the potential for a vaccine development. However,
some patients in the human clinical trials developed symptoms of brain
inflammation, demonstrating the high risk of a deliberately induced auto-immune
response.
5306.
Tiroumourougane
SV, Raghava P, Srinivasan S. Japanese viral encephalitis. Postgrad Med J 2002 Apr;78(918):205-15
One of the leading causes of acute
encephalopathy in children in the tropics is Japanese encephalitis (JE).
Transmitted by the culex mosquito, this neurotropic virus predominately affects
the thalamus, anterior horns of the spinal cord, cerebral cortex, and
cerebellum. It mainly affects children <15 years and is mostly asymptomatic.
The occasional symptomatic child typically presents with a neurological
syndrome characterised by altered sensorium, seizures, and features of
intracranial hypertension. Aetiological diagnosis is based on virus isolation
or demonstration of virus specific antigen or antibodies in the cerebrospinal
fluid/blood. Though no antiviral drug is available against JE, effective
supportive management can improve the outcome. Control of JE involves efficient
vector control and appropriate use of vaccines.
Drugs:
5307.
Dhib-Jalbut
S. Mechanisms of action of interferons and glatiramer acetate in multiple
sclerosis. Neurology 2002 Apr 23;58(8 Suppl
4):S3-9
MS is an immunologically mediated disease,
as determined by observation of the response to immunotherapy and the existence
of an animal model, experimental autoimmune encephalitis. Interferon (IFN)
beta-1b, IFN beta-1a, and glatiramer acetate, the therapies used for relapsing
or remitting MS, have mechanisms of action that address the immunologic
pathophysiology of MS. The IFNs bind to cell surface-specific receptors,
initiating a cascade of signaling pathways that end with the secretion of antiviral,
antiproliferative, and immunomodulatory gene products. Glatiramer acetate, a
synthetic molecule, inhibits the activation of myelin basic protein-reactive T
cells and induces a T-cell repertoire characterized by anti-inflammatory
effects. Although the two classes of drugs have some overlapping mechanisms of
action, the IFNs rapidly block blood-brain barrier leakage and gadolinium (Gd)
enhancement within 2 weeks, whereas glatiramer acetate produces less rapid
resolution of Gd-enhanced MRI activity. IFN beta has no direct effects in the
CNS, but glatiramer acetate-specific T cells are believed to have access to the
CNS, where they can exert anti-inflammatory and possibly neuroprotective
effects.