Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance?
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Cerebrospinal fluid (CSF) specimens from 22 allogeneic bone marrow transplant patients with central nervous system (CNS) symptoms (cases) and 107 patients who were immunocompromised but did not have CNS symptoms (controls) were assayed for human herpesvirus 6 (HHV-6) DNA. HHV-6 DNA was detected in CSF specimens from five (23%) of 22 cases and in CSF specimens from one (0.9%) of 107 controls (P < .001, Fisher's exact test). In addition, none of the five cases with HHV-6 DNA detected in CSF samples had any other identified cause of their CNS symptoms, and none of the other 11 cases with known causes for their CNS diseases had HHV-6 DNA detected in CSF samples (P = .03, Fisher's exact test). In three cases, HHV-6 variant B was identified, and the HHV-6 variant could not be defined in the other two cases. Prophylaxis with acyclovir did not prevent the occurrence of HHV-6-associated CNS disease after allogeneic bone marrow transplantation. Four cases' conditions were improved or they were cured after treatment with either ganciclovir or foscarnet, and one case died of CNS disease despite foscarnet treatment. (+info)
Acute symptomatic seizures - incidence and etiological spectrum: a hospital-based study from South India.
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We analysed the incidence and etiological spectrum of acute symptomatic seizures in 2531 patients with seizure disorder, both in-patients and out-patients, seen in a university hospital in South India. Seizure(s) occurred in close temporal association with an acute systemic, metabolic, or toxic insult or in association with an acute central nervous system (CNS) insult in 22.5% of patients. Of the 572 patients, 8% could be grouped under the International League Against Epilepsy (ILAE) category 4.1 and 92% under category 1.2. The seizure type was generalized in all the patients included in category 4.1 and 78% of patients grouped in category 2.1 had simple or complex partial seizure(s) with or without secondary generalization. Sixteen (3%) patients developed status epilepticus during the acute phase of illness and 7% of patients had only single seizure. Infections of the central nervous system (CNS) and single CT enhancing lesions (SCTEL) together accounted for 77% of the provoking factors in patients grouped under category 2.1. These two etiological factors together accounted for 95% of etiologies in patients aged under 16 years. SCTEL and neurocysticercosis together accounted for 67% of the provoking factors. In 14% of patients cerebrovascular diseases were the etiological factors and 60% of the patients were aged over 40 years. In patients with cerebrovascular diseases, aged under 40 years, cortical sinovenous thrombosis accounted for 37%. SCTEL was the provoking factor in 61% of patients with isolated seizure. Infections of CNS and SCTEL together accounted for 62.5% of etiological factors for status epilepticus. This study illustrates that the etiological spectrum of acute symptomatic seizures in this part of the world is different from that described from developed countries and CNS infections account for a significant number of cases. (+info)
The mumps virus neurovirulence safety test in Rhesus monkeys: a comparison of mumps virus strains.
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Wild type mumps viruses are highly neurotropic and a frequent cause of aseptic meningitis in unvaccinated humans. To test whether attenuated mumps viruses used in the manufacture of mumps vaccines have neurovirulent properties, a monkey neurovirulence safety test (MNVT) is performed. However, results with several mumps virus MNVTs have raised questions as to whether the test can reliably discriminate neurovirulent from nonneurovirulent mumps virus strains. Here, various mumps virus strains representing a wide range of neuropathogenicity were tested in a standardized MNVT. A trend of higher neurovirulence scores was observed in monkeys inoculated with wild type mumps virus versus vaccine strains, although differences were not statistically significant. Results indicated the need for further examination and refinement of the MNVT or for development of alternative MNVTs. (+info)
Tuberculosis of the central nervous system.
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Tuberculous involvement of the brain and spinal cord are common neurological disorders in developing countries and have recently shown a resurgence in developed ones. Tuberculous meningitis is an important manifestation and is associated with high morbidity and mortality. Diagnosis is based on clinical features, cerebrospinal fluid changes, and imaging characteristics. Bacteriological confirmation is not possible in all cases as serological tests do not have sufficient sensitivity and specificity. The polymerase chain reaction shows promise for the future. Appropriate chemotherapeutic agents should be administered as early as possible, although there is no unanimity concerning chemotherapeutic regimens or optimal duration of treatment. The patient's clinical stage at presentation is the most important prognostic factor. The role of corticosteroids is controversial but they should be administered to all patients presenting in stage III. Surgical procedures are directed at management of the hydrocephalus. Focal lesions, intracranial tuberculomas, and tuberculous abscesses, are usually located in cerebral or cerebellar hemispheres, uncommonly in brainstem and very rarely in spinal cord. They do not usually require surgical intervention and respond well to antituberculous treatment, along with corticosteroids. (+info)
Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease.
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Measles virus (MV) infects 40 million persons and kills one million per year primarily by suppressing the immune system and afflicting the central nervous system (CNS). The lack of a suitable small animal model has impeded progress of understanding how MV causes disease and the development of novel therapies and improved vaccines. We tested a transgenic mouse line in which expression of the MV receptor CD46 closely mimicked the location and amount of CD46 found in humans. Virus replicated in and was recovered from these animals' immune systems and was associated with suppression of humoral and cellular immune responses. Infectious virus was recovered from the CNS, replicated primarily in neurons, and spread to distal sites presumably by fast axonal transport. Thus, a small animal model is available for analysis of MV pathogenesis. (+info)
Neuropathogenesis of simian immunodeficiency virus in neonatal rhesus macaques.
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Neonatal human immunodeficiency virus (HIV) infection usually occurs intrapartum or postpartum and results in a higher incidence of neurological dysfunction than is seen in adults. To explore the neuropathogenesis of neonatal HIV infection, we infected neonatal macaques with simian immunodeficiency virus (SIV) and followed the course of infection focusing on early time points. Infected neonates had decreased brain growth and mild histological changes in brain that resembled those seen in pediatric AIDS, including perivascular infiltrates of mononuclear cells, mineralization of vessels in the basal ganglia, and gliosis. The perivascular lesions and gliosis were associated with the presence of occasional infected cells that required in situ hybridization with radiolabeled riboprobes for detection. Using this technique, SIV-infected cells were detected in the brain parenchyma within 7 days of infection. These findings were confirmed by nested PCR for SIVgag DNA in brain and RT-PCR for viral RNA in cerebrospinal fluid. Together, these techniques revealed SIV infection of the CNS in 12 of 13 neonates infected with SIVmac239, 3 of 3 infected with SIVmac251, and 2 of 2 infected with SIVmac239/316. The prevalence of CNS infection was indistinguishable from that of older animals infected with the same dose and stock of virus, but neonates appeared to have fewer infected cells in the CNS and detecting them required more sensitive techniques. This observation was true regardless of inoculum and despite the fact that neonates had equal or greater viral loads in the periphery compared with older animals. These data suggest that maturation-dependent host factors have a major impact on the neuropathogenesis of pediatric AIDS. (+info)
Outpatient parenteral antimicrobial therapy for central nervous system infections.
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Patients with central nervous system (CNS) infections are increasingly treated with intravenous antimicrobials outside the hospital, but the safety and problems associated with this therapy have not been well defined. To examine this issue, we reviewed 68 cases in which outpatient intravenous antimicrobial therapy (OPAT) was received through our physician office-based infusion clinic. All infections were cured, and no deaths occurred during therapy. Seizures occurred in 2 patients but without significant injury and apparently were unrelated to antimicrobial therapy. Eleven patients (16%) were hospitalized after starting OPAT, 5 for procedures and 6 for medical reasons. The antimicrobial used was changed in 13 cases (19%) because of an adverse effect or clinical failure. OPAT can be safe and effective for patients with CNS infections, but patients must be carefully selected and monitored closely. (+info)
Effective use of polymerase chain reaction for diagnosis of central nervous system infections.
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Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) specimens has become standard for confirmatory diagnosis of central nervous system (CNS) infections; however, these tests increase health care costs. We reviewed 3-year data from 974 consecutive CSF specimens submitted for detection of seven pathogens by PCR. In 1997, 237 of 367 specimens (64.6%) were submitted for multiple tests, compared with 203 of 522 (38.9%) in 1996 and 18 of 85 (21.2%) in 1995. In each year the arrival of new house officers coincided with a peak in multiple testing. Among 732 specimens submitted for herpesvirus detection, results were positive for 24 (4.6%) of 523 specimens with increased leukocyte counts or protein levels. None of 209 specimens with normal leukocyte and protein levels were positive for herpesviruses. None of 471 CSF specimens submitted for Borrelia burgdorferi detection were PCR-positive. Use of protein and leukocytes to screen CSF specimens before employing PCR for herpesvirus detection would save almost one-third of costs without reducing sensitivity. (+info)