Intrathecal methotrexate overdose without neurotoxicity: case report and literature review

A 24-month-old female developed a central nervous system relapse, while in bone marrow remission, eight months after the diagnosis of acute lymphocytic leukemia was made. Inadvertently, she received 14 times the standard dose of intrathecal methotrexate (170 mg/m2 vs. 12 mg/m2). Treatment with intravenous leucovorin and oral dexamethasone was given. Her only symptomatology was mild headaches. No neurological abnormalities developed. Her cerebrospinal fluid methotrexate levels (5.2 X 10(-6)M at 23 hours and 5.9 X 10(-7)M at 47 hours) and half-life (t 1/2 = 8 hours) were within the range previously reported in patients following standard doses of intrathecal methotrexate who did not develop neurotoxicity. The various manifestations of neurotoxicity associated with the use of intrathecal methotrexate as well as those factors considered to play a part in the development of neurotoxicity are reviewed.