Infections of the CNS with the nonpolio enteroviruses are common and important causes of morbidity in both children and adults. Studies have recently defined the short-term and long-term outcomes of aseptic meningitis due to the enteroviruses. Focal encephalitis is increasingly recognized as a complication of enterovirus infection. Patients at greatest risk for sequelae of CNS enteroviral disease include neonates and those who are immunocompromised. The clinical presentation may mimic that of bacterial or other viral CNS infections, a circumstance making laboratory diagnosis of paramount importance for reducing unnecessary hospitalization and therapy. Recent advances in PCR technology, including its adaptation to a colorimetric microwell plate format, promise to greatly facilitate diagnosis of enteroviral infections. Promising antiviral drugs for CNS disease and other serious manifestations of enteroviral infections are under development.

Enteroviruses usually cause self-limited disease that, although associated with high morbidity, is rarely fatal. In certain patient populations, however, the enteroviruses may cause potentially life-threatening infections. Pleconaril is a novel compound that integrates into the capsid of picornaviruses, including enteroviruses and rhinoviruses, preventing the virus from attaching to cellular receptors and uncoating to release RNA into the cell. Pleconaril was used on a compassionate-release basis to treat patients with potentially life-threatening enterovirus infections, and for 38 of these patients sufficient follow-up data were available for determining responses to therapy. Response was evaluated in 4 categories: clinical, virological, laboratory, and radiological. Most patients (28 [78%] of 36), including 12 of 16 with chronic enterovirus meningoencephalitis, were judged to have a clinical response temporally associated with pleconaril therapy. Similarly, nearly all patients whose virological responses (12 [92%] of 13), laboratory responses (14 [88%] of 16), and radiological responses (3 [60%] of 5) could be evaluated were judged to have responded favorably to a course of pleconaril treatment. Adverse effects were minimal and the drug was generally well-tolerated.

Enteroviruses account for 85 to 95% of all cases of aseptic meningitis, but the arboviruses and herpes simplex virus are also important etiologic agents. Mumps, lymphocytic choriomeningitis virus, herpes zoster, human herpesvirus type 6, and influenza viruses are rare causes of meningitis. The virology, pathogenesis, epidemiology, clinical manifestations, diagnostic studies, and established and potential antiviral therapies for viral meningitis are discussed. A differential diagnosis of the aseptic meningitis syndrome is provided.

A prospective study of the virology of and serological responses to enterovirus infection in 16 neonates (< or = 2 weeks of life) and their mothers was performed. At study entry, 11 neonates did not have detectable serum neutralizing antibody to their own viral isolates, despite the presence of neutralizing antibody in 9 of 11 mothers of these infants. Viremia and viruria were demonstrated in 8 and 7 neonates, respectively, with maximal detected titers of 6.3 x 10(3) 50% tissue culture infective dose per mL (TCID50) and 6.8 x 10(1) TCID50/mL, respectively. Viremia was associated with onset of illness in the first 5 days of life, low initial serum neutralization titer, and the presence of echovirus serotypes. Randomized administration of intravenous immune globulin (IVIG; 750 mg/kg) to nine neonates overall modestly increased serum neutralization titers but did not reduce the daily incidence of viremia and viruria compared with that of controls. However, receipt of IVIG containing a neutralization titer of > or = 1:800 to the patients' own viral isolates was associated with significantly higher serum neutralization titers and more rapid cessation of viremia and viruria. Future trials of IVIG for neonatal enterovirus disease should assess the efficacy and safety of higher or repeated doses of this agent and/or of IVIG selected for their high titers to frequently circulating and/or particularly virulent enterovirus serotypes.

Enteroviruses are among the most common causes of childhood infection. Current diagnostic techniques are often too slow and too insensitive to benefit the patient optimally. This report describes a modified polymerase chain reaction technique by which enteroviral RNA can be amplified, over a few hours, to a level detectable by agarose mini-gel electrophoresis or nucleic acid hybridization or both. Three oligomeric regions of great homology among the enteroviruses were identified and designated as a potential primer pair and probe. With this combination, all 11 of the enterovirus serotypes tested, representing the major subgroups of these pathogens, were successfully amplified and detected. The sensitivity and rapidity of this new assay speak to its potential clinical applicability in the diagnosis of enterovirus infections.