1 New Haven, Connecticut
The studies of Bleyer and co-workers indicate an association between high cerebrospinal fluid antifolate levels and subsequent neurological damage following intrathecal methotrexate administration. Clinically, neurotoxicity has been ascribed to intrathecal methotrexate or its preservatives in several series. Symptoms and signs occur within hours to a few days after intrathecal administration. Since the CSF half-life of methotrexate is three to six days, encephalopathy appearing more than two weeks from the time of intrathecal therapy is unlikely to be due to direct toxic effects.