Ribavirin is a broad-spectrum
antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with
subacute sclerosing panencephalitis (
SSPE) were treated with
ribavirin by intraventricular administration. Although there were transient side effects attributed to
ribavirin, such as drowsiness,
headache, lip and gingival swelling, and conjunctival
hyperemia, intraventricular
ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF)
ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable interindividual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of
ribavirin in the CSF in order to maintain the CSF
ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition
antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF
ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of
ribavirin is effective against
SSPE if the CSF
ribavirin concentration is maintained at a high level. Intraventricular
ribavirin therapy should be pursued further for its potential use for patients with
SSPE and might be applied in the treatment of patients with
encephalitis caused by other RNA viruses.