December 22, 2022
A 59-year-old woman with metastatic breast cancer presents to the emergency department 2 days after beginning treatment with capecitabine with loss of coordination, acute confusion, and muscle weakness.
Capecitabine-Induced Acute Toxic Leukoencephalopathy
- Background:
- Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity used in the treatment of metastatic breast and colorectal cancers. It is a prodrug, which is enzymatically converted to fluorouracil in the tumor cells where it inhibits DNA synthesis and slows the growth of tumor tissue.
- Capecitabine is currently the only universally approved orally administered 5-fluorouracil (5-FU) prodrug.
- Acute multifocal leukoencephalopathy is rare.
- Dyhydropyrimidine dehydrogenase deficiency is responsible for more than 85% of the catabolism of pyrimidine and may be a risk factor for 5-FU-induced leukoencephalopathy.
- Clinical Presentation:
- Symptoms of neurotoxicity usually include confusion, ataxia, nystagmus, dysarthria, sensory loss, and memory loss.
- Severe toxicity, such as bone marrow suppression and gastrointestinal mucositis, has been described.
- Key Diagnostic Features:
- It is common that lesions seen on MR imaging are located mainly in the deep white matter and the corpus callosum.
- MRI with diffusion-weighted imaging may show restricted diffusion. Subtler changes may be seen on FLAIR and T2 sequences.
- Differential Diagnoses:
- Paraneoplastic demyelinating disorders are not reversible, and they worsen without treatment.
- Posterior reversible encephalopathy syndrome (PRES) is radiologically characterized by diffuse hyperintensity in the posterior parietal and occipital white matter. The gray matter also can also be involved occasionally. Clinically, patients with PRES present with seizures, altered mental status, and headache.
- Due to the clinical presentation and in the context of neoplasia, brain metastases or paraneoplasic demyelinating disorders could have appeared on imaging, too, but the results of the MRI rapidly excluded such differential diagnoses.
- Treatment:
- Supportive and anecdotal treatments: trial of immunotherapy (eg, corticosteroids, IVIG), early hypothermia, antiviral agents, anticonvulsants
