Cause Of Central Nervous System Infection Research Articles

Human Herpesviruses 6 and 7 and Central Nervous System Infection in Children1

The role and frequency of human herpesviruses (HHV)-6 and -7 in central nervous system (CNS) diseases of children are unclear. Cerebrospinal fluid samples from 245 pediatric patients (median age 43 days), submitted for evaluations of possible sepsis or of neurologic symptoms, were tested for HHV-6 and HHV-7 DNA by polymerase chain reaction. HHV-6 DNA was found in 3 of 245 samples, and HHV-7 was found in 0 of 245 samples. The three patients with HHV-6 DNA were <2 months of age. HHV-6 was likely pathogenic in two patients with meningitis who lacked evidence of another microbiologic cause. HHV-6 and HHV-7 are uncommon causes of CNS infection in children. HHV-6 may occasionally cause meningitis in young infants.

Viral meningitis and encephalitis: Traditional and emerging viral agents

In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS disease. As a result of increased testing for WNV, lesser known viral causes of CNS infection have been identified. Even the epidemiology of such traditional viral neuropathogens as rabies has changed in recent years. This review provides an overview of viruses traditionally associated with meningitis and encephalitis (enteroviruses, La Crosse virus, St. Louis encephalitis virus, eastern and western equine viruses, varicella-zoster virus), as well as several of the less common (Powassan virus, lymphocytic choriomeningitis virus, Colorado tick fever virus, rabies virus, influenza viruses, etc.) and emerging (West Nile virus) viral pathogens. © 2003 Elsevier Inc. All rights reserved.

Quantitative CSF PCR in Epstein-Barr virus infections of the central nervous system.

Acute Epstein-Barr virus (EBV) infection of the central nervous system (CNS) is associated with meningoencephalitis and other neurological syndromes and with CNS lymphomas (CNSLs). Diagnosis is based on serological studies and more recently on detection of EBV DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR). We measured EBV DNA by quantitative PCR and EBV mRNA by RT-PCR in the CSF in patients with EBV-associated neurological disorders. EBV was identified as the cause of CNS infection in 28 patients: 14 with CNSL, 10 with encephalitis, and 4 with postinfectious neurological complications. CSF analysis showed that patients with CNSL had high EBV load (mean +/- standard error of 4.8 +/- 0.2 log(10) DNA copies/ml) and low leukocyte counts (22 +/- 7 cells/microl); encephalitis was characterized by high EBV load (4.2 +/- 0.3 log(10) DNA copies/ml) and high leukocyte counts (143 +/- 62 cells/microl); and patients with postinfectious complications showed low EBV load (3.0 +/- 0.2 log(10) DNA copies/ml) with high leukocyte counts (88 +/- 57 cells/microl). Lytic cycle EBV mRNA, a marker of viral replication, was identified in 10 CSF samples from patients with CNSL and encephalitis. These studies demonstrate the utility of quantitative CSF PCR and establish the presence of lytic cycle EBV mRNA in CSF of patients with EBV-associated neurological disease.

Molecular Techniques in the Diagnosis of Central Nervous System Infections.

Development of polymerase chain reaction (PCR)-based molecular techniques has initiated a revolution in the field of diagnostic microbiology. These techniques have not only provided rapid, noninvasive detection of microorganisms that cause central nervous system (CNS) infections, but have also demonstrated that several neurologic disorders are linked to infectious agents. While PCR-based techniques are predicted to be widely used in diagnosing and monitoring CNS infections, the limitations, as well as strengths, of these techniques must be clearly understood by both clinicians and laboratory personnel to ensure proper utilization.

Targeting apoptosis in neurological disease using the herpes simplex virus.

Herpes Simplex Viruses type 1 (HSV-1) and 2 (HSV-2) cause central nervous system (CNS) disease ranging from benign aseptic meningitis to fatal encephalitis. In adults, CNS infection with HSV-2 is most often associated with aseptic meningitis while HSV-1 frequently produces severe, focal encephalitis associated with high mortality and morbidity. Recent studies suggested that the distinct neurological outcome of CNS infection with the two viruses may be due to their distinct modulation of apoptotic cell death: HSV-1 triggers neuronal apoptosis, while HSV-2 is neuroprotective. Apoptosis also occurs in the etiology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Down's syndrome, and determines the loss of specific neuronal populations and the decline in cognitive functions. Notwithstanding, the therapy of these disorders may rely on the use of replication-defective HSV-1 vectors to deliver anti-apoptotic transgenes to the CNS. However, the recent discovery of a neuroprotective activity innate to the HSV-2 genome (the ICP10 PK gene) suggests that: i) ICP10 PK may constitute a novel therapeutic approach by targeting both the apoptotic cell death and the cognitive decline, and ii) HSV-2 may be more suitable than HSV-1 as a vector for targeting neuronal disease.

Parainfluenza Type 3 Meningitis

The authors present two immunocompetent children with parainfluenza type 3 meningitis. In each case, the outcome was favorable without detectable complications. The authors reviewed the literature, showing that central nervous system (CNS) involvement by parainfluenza viruses has rarely been described but may present with a variety of neurologic syndromes. Pediatricians and laboratory personnel should recognize that these viruses, commonly known to produce respiratory syndromes, can also be a cause of CNS infections. If additional studies confirm these observations, clinicians and virology laboratories may consider whether early hemadsorption testing to detect myxoviruses is warranted.