Reversible posterior leukoencephalopathy syndrome associated with mFOLFOX6 chemotherapy

Abstract

Reversible posterior leukoencephalopathy syndrome (RPLS) is a serious neurologic disease characterized by visual disturbance, seizures, headache, and altered mental status associated with white matter changes, particularly in the occipital lobes. RPLS has been attributed to chemotherapy, including modified FOLFOX6 regimens consisting of 5-fluorouracil, oxaliplatin, and leucovorin. Although the mechanism of development of RPLS remains unclear, impaired cerebral blood flow autoregulation and endothelial dysfunction seem to be involved. In particular, endothelial dysfunction has been implicated in the pathophysiology of RPLS associated with platinum agents. Platinum-based chemotherapy is thought to have a direct toxic effect on the vascular endothelium, leading to capillary leakage, disruption of the blood–brain barrier, and axonal swelling, triggering vasogenic edema. Much progress has been made in chemotherapy for colorectal cancer, and the increasing use of molecular-targeted agents is expected to further improve the outcome of therapy. RPLS has recently been associated with such molecular-targeted therapy, particularly in patients concurrently receiving platinum agents. This finding is consistent with previous reports suggesting that RPLS occurs more often in patients receiving platinum-based therapy than in those receiving molecular-targeted agents. Because platinum agents are the most widely used in cancer chemotherapy, clinicians should strongly suspect RPLS in patients receiving treatment with this class of drug.