Role of the virology laboratory in diagnosis and management of patients with central nervous system disease

Abstract

A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection.

Detection of neurotropic viruses circulating in Tuscany: The incisive role of Toscana virus

“…The predominant causative or associated viral agents of meningitis are enteroviruses, flaviviruses, bunyaviruses, mumps virus, measles virus, herpes simplex virus types 1 and 2, herpes zoster virus, adenovirus, cytomegalovirus, lymphocytic choriomeningitis virus, and Epstein-Barr virus [Deibel et al, 1979;Bergstrom et al, 1990;Soeur et al, 1991;Shoji et al, 1992;Kaji and Shoji, 1995;Kudelova et al, 1995;Cusi et al, 1996;Luzi et al, 1997;Valassina et al, 1996;Rousseau et al, 1997;Gorgievski-Hrisoho et al, 1998;Rotbart et al, 1998;Tsai et al, 1998]. Standard diagnostic procedures, such as viral culture or serology, are often insufficient for the circumstantial or retrospective identification of a viral infection of the central nervous system [Chonmaitree et al, 1989]. Molecular techniques appear to be valid support useful for the accurate detection of the viral agent in the CSF, considering the rapidity of execution and their sensitivity [Hosoya et al, 1998;Read and Kurtz, 1999].…”

New Reverse Transcription-PCR Assay for Rapid and Sensitive Detection of Enterovirus Genomes in Cerebrospinal Fluid Specimens of Patients with Aseptic Meningitis

“…Prior studies comparing cell culture and PCR assays for EV detection have demonstrated that the use of PCR techniques significantly increases the rates of detection of EV in CSF samples of patients with aseptic meningitis or other neurological syndromes (6,7,16). The low rate of EV detection by cell culture compared with results obtained by RT-PCR assays may be explained either by low viral loads in CSF, by the presence of infectious EVs that grow poorly or not at all in classical cell cultures, or by the presence of replication-defective or antibody-neutralized viruses unable to propagate in cell culture (3,4,12).…”

“…Aseptic meningitis is the most common EV-related central nervous system syndrome and may be difficult to distinguish from meningitis caused by herpesviruses or bacteria, particularly in young infants and children (9,10). When classical cell culture techniques are used, attempts to isolate EVs from cerebrospinal fluid (CSF) samples are frequently unsuccessful because of the low viral titers in clinical specimens and because some serotypes grow poorly in cell culture (3,4). Therefore, in-house PCR techniques for the detection of the EV genome have been introduced, allowing sensitive and rapid identification of EV-infected CSF samples (1,11,12,17) and improving the management of young infants with meningitis (8).…”

Highly Sensitive Assay for Detection of Enterovirus in Clinical Specimens by Reverse Transcription-PCR with an Armored RNA Internal Control

“…A reliable means of laboratory detection of EV is needed, since the specific and rapid diagnosis of EV meningitis has a significant impact on patient management (10). Although reverse transcription (RT)-PCR may become the method of choice for the diagnosis of EV infections of the central nervous system, in many laboratories the diagnosis of EV infections still relies on cell culture techniques.…”