Methotrexate treatment protocols and the central nervous system: Significant cure with significant neurotoxicity

Methotrexate can influence the central nervous system through several metab olic toxic pathways. These effects can be categorized as immediate, acute t o subacute, or chronic neurologic syndromes. The acute to subacute syndrome occurs frequently in acute lymphoblastic leukemia treatment protocols, gen erally manifesting with focal neurologic signs and changes seen on magnetic resonance imaging and single photon emission computed tomography. While in some patients the neurotoxicity is transient and benign and allows for con tinuation of chemotherapy, in others it can be quite severe and debilitatin g, leading to permanent neurologic deficits. The need to modify the treatme nt protocols when neurotoxicity appears is not fully established. It is als o unknown whether the use of sufficient amounts of leucovorin can overcome the toxic effects of the drug.