UMLS:C0014070 - FACTA Search

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Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recovery from viral encephalomyelitis requires immune-mediated noncytolytic clearance from neurons by mechanisms assumed to be the same for all neurons. In alphavirus encephalomyelitis, antibody clears infectious virus from neurons in all regions of the central nervous system (CNS), but CD8 T cells contribute to elimination of viral RNA. To understand the role of T cells in clearance, we infected antibody knockout mice with Sindbis virus. Virus was cleared from spinal cord and brain stem neurons, but not from cortical neurons, and required both CD4 and CD8 T cells. Infection with cytokine-expressing recombinant viruses suggested that T cells used interferon-gamma, but not tumor necrosis factor alpha, in clearing virus and that populations of neurons differ in responsiveness to this effector pathway.
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PMID:Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons. 1145 26

Molecular mimicry is the process by which virus infection activates T cells that are cross-reactive with self antigens. Infection of SJL/J mice with the neurotropic picornavirus Theiler's murine encephalomyelitis virus (TMEV) leads to a progressive CD4(+) T cell-mediated demyelinating disease similar to multiple sclerosis. To study the potential of virus-induced molecular mimicry to initiate autoimmune demyelination, a nonpathogenic TMEV variant was engineered to encode a 30-mer peptide encompassing the immunodominant encephalitogenic myelin proteolipid protein (PLP139-151) epitope. Infection with the PLP139-151-encoding TMEV led within 10-14 days to a rapid-onset paralytic demyelinating disease characterized by PLP139-151-specific CD4(+) Th1 responses; insertion of a non-self ovalbumin sequence led to restoration of the normal late-onset disease. Early-onset disease was also observed in mice infected with a TMEV encoding PLP139-151 with an amino acid substitution at the secondary T cell receptor (TCR) contact residue (H147A), but not in mice infected with TMEV encoding a PLP139-151 substitution at the primary TCR contact (W144A). Most significantly, mice infected with TMEV encoding a Haemophilus influenzae mimic peptide, sharing only 6 of 13 amino acids with PLP139-151, displayed rapid-onset disease and developed cross-reactive PLP139-151-specific CD4(+) Th1 responses. To our knowledge, this is the first study showing that a naturally infectious virus encoding a myelin epitope mimic can directly initiate organ-specific T cell-mediated autoimmunity.
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PMID:A virus-induced molecular mimicry model of multiple sclerosis. 1145 84

A 17-year-old boy presented with a severe form of an acute disseminated encephalomyelitis (ADEM) with hemiparesis and coma after initial symptoms of a flu-like febrile infection 1 week previously. Titers against Mycoplasma pneumoniae were significantly increased in serum and cerebrospinal fluid (CSF). Detection of M. pneumoniae was achieved in the initial CSF sample using M. pneumoniae-specific PCR. The patient improved significantly on antimicrobial therapy with erythromycin and immunosupressive therapy with immunoglobulins and corticosteroids. This case report demonstrates a well-documented course of a central nervous system (CNS) infection resulting in the ADEM syndrome.
Infection 2001 Aug
PMID:Acute disseminated encephalomyelitis (ADEM) due to Mycoplasma pneumoniae infection in an adolescent. 1154 90

Infection by the neurotropic JHM strain of mouse hepatitis virus produces an acute demyelinating encephalomyelitis. While cellular immunity initially eliminates infectious virus, CNS viral persistence is predominantly controlled by humoral immunity. To better understand the distinct phases of immune control within the CNS, the kinetics of humoral immune responses were determined in infected mice. Early during clearance of the JHM strain of mouse hepatitis virus, only few virus-specific Ab-secreting cells (ASC) were detected in the periphery or CNS, although mature B cells and ASC without viral specificity were recruited into the CNS concomitant with T cells. Serum antiviral Ab and CNS virus-specific ASC became prominent only during final elimination of infectious virus. Virus-specific ASC peaked in lymphoid organs before the CNS, suggesting peripheral B cell priming and maturation. Following elimination of infectious virus, virus-specific ASC continued to increase within the CNS and then remained stable during persistence, in contrast to declining T cell numbers. These data comprise three novel findings. Rapid recruitment of B cells in the absence of specific Ab secretion supports a potential Ab-independent effector function involving lysis of virus-infected cells. Delayed recruitment relative to viral clearance and subsequent maintenance of a stable CNS ASC population demonstrate differential regulation of T and B lymphocytes within the infected CNS. This supports a critical role of humoral immunity in regulating viral CNS persistence. Lastly, altered antiviral ASC specificities following clearance of infectious virus suggest ongoing recruitment of peripheral memory cells and/or local B cell differentiation.
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PMID:Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis. 1188 63

Infection of mice by low-neurovirulence Theiler's murine encephalomyelitis virus (TMEV), such as BeAn and DA viruses, provides a relevant experimental animal model for multiple sclerosis (MS). As a step toward determining the kinetics of a persistent central nervous system (CNS) infection that leads to chronic demyelination, we adapted a rapid, accurate and highly specific real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection and quantitation of BeAn virus RNA copy equivalents in mouse tissues. The assay enabled detection of as few as 20-30 copies of BeAn virus RNA per microg of total RNA from infected mouse tissues and results for spinal cord revealed the same high levels of BeAn RNA as detected by Northern hybridization during the first 4 months of the persistent infection, but also was able to detect virus RNA copies as late as 1 year post-infection. Real-time RT-PCR analysis of BeAn virus RNA copy equivalents in different parts of the CNS, analyses not possible by Northern hybridization, revealed the following cline of virus persistence: spinal cord>brainstem/cerebellum>cerebrospinal fluid (CSF)>cerebral hemispheres. Systemic organs, including heart, intestine and mesenteric lymph nodes of infected mice, showed no evidence of viral persistence at 4 months post-infection.
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PMID:Enhanced detection of Theiler's virus RNA copy equivalents in the mouse central nervous system by real-time RT-PCR. 1190 36

Infection of the central nervous system (CNS) of susceptible mice with mouse hepatitis virus (MHV), a positive-strand RNA virus that is a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis followed by a demyelinating disease similar to the human demyelinating disease multiple sclerosis (MS). MHV infection triggers a robust cell-mediated response in which both CD4+ and CD8+ T cells are essential in controlling viral replication and spread. However, viral clearance is incomplete and viral RNA and protein can persist within white matter tracts, areas of viral persistence are often associated with demyelinating lesions, and recent studies have indicated an important role for both T cells and macrophages in contributing to myelin destruction. The molecular mechanisms governing leukocyte trafficking and accumulation within the CNS of MHV-infected mice are just now being understood and recent studies indicate that chemokines and chemokine receptors have an important role in this process. This article will provide an overview on how these molecules regulate T cell and macrophage trafficking into the CNS of MHV-infected mice and illustrate the delicate balance that exists with regards to expression of chemokines and their receptors as it relates to both host defense and disease development.
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PMID:Mouse hepatitis virus infection of the central nervous system: chemokine-mediated regulation of host defense and disease. 1208 Oct 11

The neurotoxic effects of immunosuppressive agents used after transplantation are well known. In most cases a decrease in drug dosage results in resolution of the neurotoxicity. At early stages in the post-transplantation clinical course, neurotoxicity and other complications such as infectious disease, encephalopathy and seizures are sometimes difficult to diagnose with neuroimaging. Recently, diffusion weighted imaging (DWI) has been used in patients with ischemic disease, mitochondrial myopathy, encephalopathy and demyelinating disease. We examined the magnetic resonance images (MRI), including DWI and fluid attenuated inversion recovery image (FLAIR), in three cases of post-transplantation neurological complication: two cases of neurotoxicity and a case of acute disseminated encephalomyelitis (ADEM). Hyper-intense lesions representing neurotoxicity were seen on FLAIR but not on DWI in two cases with neurotoxicity induced by an immunosuppressive agent. In ADEM, hyper-intense lesions were seen on both FLAIR and DWI. Neurotoxicity due to the immunosuppressive agent showed a favorable outcome, although the hyper-intense lesions temporally presented on FLAIR. In the state after transplantation, hyper-intense lesions on FLAIR and DWI represented in the brain from the initial stage, we might be care of other severe complications but for neurotoxicity.
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PMID:Magnetic resonance imaging in cases with encephalopathy secondary to immunosuppressive agents. 1209 40

In the new Japanese control law for infectious diseases, most varieties of acute viral encephalitis belong to Category IV requiring report of all cases at sentinel hospitals. Herpes simplex virus type 1 (HSV-1) encephalitis comprises the majority of cases. With the increased prevalence of diagnostic procedures such as polymerase chain reaction (PCR), several forms of HSV-1, and -2 central nervous system (CNS) infections, including acute disseminated encephalomyelitis, brainstem encephalitis, and myelitis, have been clarified. Since 1990 we have conducted a survey of HSV CNS infections in the Kyushu and Okinawa regions, and the data are reviewed here. Trends include an increase in a new subtype of non-herpetic acute limbic encephalitis. In contrast, the incidence of Japanese encephalitis (JE) in Japan has dramatically decreased to a few patients per year; however, JE remains a threat for those with decreased or absent immunity to the JE virus. Imported emerging and reemerging CNS infections such as Murray Valley and West Nile encephalitis can occur in Japan. Influenza-associated encephalitis/encephalopathy is also described as a threat for adults as well as young children.
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PMID:Acute viral encephalitis: the recent progress. 1213 72

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.
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PMID:Smallpox vaccination and adverse reactions. Guidance for clinicians. 1261 10

Theiler's virus infection in the central nervous system (CNS) induces a demyelinating disease very similar to human multiple sclerosis. We have assessed cytokine gene activation upon Theiler's murine encephalomyelitis virus (TMEV) infection and potential mechanisms in order to delineate the early events in viral infection that lead to immune-mediated demyelinating disease. Infection of SJL/J primary astrocyte cultures induces selective proinflammatory cytokine genes (interleukin-12p40 [IL-12p40], IL-1, IL-6, tumor necrosis factor alpha, and beta interferon [IFN-beta]) important in the innate immune response to infection. We find that TMEV-induced cytokine gene expression is mediated by the NF-kappaB pathway based on the early nuclear NF-kappaB translocation and suppression of cytokine activation in the presence of specific inhibitors of the NF-kappaB pathway. Further studies show this to be partly independent of dsRNA-dependent protein kinase (PKR) and IFN-alpha/beta pathways. Altogether, these results demonstrate that infection of astrocytes and other CNS-resident cells by TMEV provides the early NF-kappaB-mediated signals that directly activate various proinflammatory cytokine genes involved in the initiation and amplification of inflammatory responses in the CNS known to be critical for the development of immune-mediated demyelination.
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PMID:Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease. 1274 89

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