CNS nontumor
Toxic and metabolic disorders
Methotrexate toxicity
Author: Kymberly A. Gyure, M.D.
Last author update: 1 January 2015
Last staff update: 2 December 2024 (update in progress)
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Methotrexate toxicity [title]
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Pathophysiology | Clinical features | Radiology description | Radiology images | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Additional referencesCite this page: Gyure K.A. Methotrexate toxicity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnsmethotrexate.html. Accessed December 23rd, 2024.
Definition / general
- Chemotherapeutic agents, either alone or combined with radiation therapy, may lead to cognitive decline with an associated leukoencephalopathy
- Most common offending agent is methotrexate, particularly when it is administered intrathecally
Terminology
- Term disseminated necrotizing leukoencephalopathy (DNL) has been applied to the progressive and fatal form of neurologic disease induced by combined intrathecal methotrexate administration and radiation (Cancer 1975;35:291)
Epidemiology
- Methotrexate is used predominantly to treat leukemia and lymphoma, including primary CNS lymphoma
- Patients treated for childhood leukemia are at particular risk for developing methotrexate related leukoencephalopathy
Sites
- Predominantly white matter
Pathophysiology
- Methotrexate is a folic acid antagonist which inhibits DNA synthesis
- It also indirectly inhibits the synthesis of methionine, which is necessary for the formation and maintenance of myelin, leading to vacuolar degeneration of white matter (Acta Neuropathol 1989;78:291)
- Most individuals with severe neurologic complications secondary to methotrexate also have a history of radiation therapy and a synergistic effect of methotrexate and radiation is considered to be likely to lead to serious damage to white matter
Clinical features
- Cognitive decline, decrease in IQ
Radiology description
- Cerebral atrophy, decreased density of white matter on CT scans, diffuse periventricular hyperintensities on T2 weighted MR images and calcifications in the basal ganglia
Radiology images
Images hosted on other servers:
Toxic leukoencephal-opathy
Neurotoxicity
Case reports
- 70 year old woman with methotrexate myelopathy with extensive transverse necrosis (Neuropathology 2014;34:547)
- Severe neurotoxicity following intrathecal methotrexate with nitrous oxide sedation in a child with acute lymphoblastic leukemia (Pediatr Blood Cancer 2015;62:539)
- Methotrexate related leukoencephalopathy without radiation therapy (Neuropathology 2009;29:105)
Treatment
- There is currently no effective treatment for methotrexate related leukoencephalopathy
Gross description
- Discrete, gray brown foci of friable white matter with associated edema
Microscopic (histologic) description
- Vacuolation or necrosis, axonal swellings (spheroids), macrophage infiltrates, gliosis
Microscopic (histologic) images
Contributed by Kymberly A. Gyure, M.D.
Methotrexate toxicity
Additional references
