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The most recent version of this article was published on 1 May 2008

J Neurol Neurosurg Psychiatry. Published Online First: 6 August 2007. doi:10.1136/jnnp.2007.123737
Copyright © 2007 by the BMJ Publishing Group Ltd.
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Original articles

Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients

Baehring J M 1* and Fulbright R K 1

1 Yale University School of Medicine, United States

* To whom correspondence should be addressed. E-mail: joachim.baehring{at}yale.edu.

Accepted 23 July 2007


*  Abstract

Background: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration.

Methods: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded.

Results: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion-weighted imaging (DWI) of all patients revealed well-demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum corresponding to areas of decreased proton diffusion on Apparent Diffusion Coefficient (ADC) maps (available in 21/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalization of ADC abnormalities. However, fluid-attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities.

Conclusions: Several pathophysiological models of subacute leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic edema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome.

Keywords: capecitabine, chemotherapy, diffusion-weighted MRI, leukoencephalopathy, methotrexate




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Chemotherapy-Induced Toxic Leukoencephalopathy
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