Toxic leukoencephalopathy

Last revised by Arlene Campos ◉ on 7 Feb 2025

Toxic leukoencephalopathy is an encephalopathy predominantly affecting white matter as a result of a toxic substance. The presentation can either be chronic or acute. In the acute phase, acute toxic leukoencephalopathy can have a characteristic and profound MR imaging appearance that is potentially reversible with therapy or removal of the offending agent.

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The clinical presentation of toxic leukoencephalopathy is extremely variable, ranging from minor cognitive impairment, easily confused with psychiatric illnesses, to severe neurological dysfunction. The lack of imaging in patients with minimal or mild encephalopathic symptoms may account for why this entity may be underdiagnosed in the acute phase. Notably, worse outcomes from acute toxic leukoencephalopathy can be seen with opiate-related insults relative to immunosuppression and hepatic/hyperammonemia-related toxic leukoencephalopathy.

There are numerous agents implicated in toxic leukoencephalopathy. These include:

  • antineoplastic drugs

    • methotrexate (10% IV, 40% intrathecal)

    • carmustine

    • cisplatin

    • cytarabine

    • fludaribine (note: the insult may occur weeks after the exposure)

    • fluorouracil (5-FU)

    • ifosfamide 6

    • thiotepa

    • interleukin-2 (IL-2)

    • interferon alpha (IFN alpha)

  • immunosuppresive drugs

    • cyclosporin

    • tacrolimus

    • cytoxan

  • antimicrobial agents

  • drugs of use

  • environmental toxins

  • cranial irradiation

  • sepsis

  • metabolic abnormalities

    • hyperglycemia

    • uremia

    • hyperammonemia (in the setting of hepatic failure)

The more common of these causes can be remembered with a mnemonic: CHOICES.

The findings are potentially reversible with therapy or removal of the offending agent in the early phase.

Patterns of signal abnormality may vary significantly depending on the exact causative toxin, but generally:

  • T2/FLAIR: white matter abnormalities are typically confluent and symmetric, and may involve the corpus callosum as well, particularly the splenium

  • DWI: white matter abnormalities are similar to FLAIR, typically confluent and symmetric, and may involve the corpus callosum as well, particularly the splenium

  • SWI: there may rarely be punctate (<5 mm size) microhemorrhages scattered throughout the periventricular white matter

  • T1 C+ (Gd): abnormal contrast enhancement may or may not be seen 6

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