tokens: The following factors appear to predispose to the development of this complication : abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia , and epidural cerebrospinal leakage ; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults ; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents ; and the use of methotrexate diluents of unphysiologic pH , ionic content and osmolarity .