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Clinical and Imaging Features of Fludarabine Neurotoxicity

Lee, Michael S MD; McKinney, Alexander M MD; Brace, Jeffrey R MD; SantaCruz, Karen MD

Journal of Neuro-Ophthalmology: March 2010 - Volume 30 - Issue 1 - pp 37-41
doi: 10.1097/WNO.0b013e3181ce8087
Original Contributions

Neurotoxicity from intravenous fludarabine is a rare but recognized clinical entity. Its brain imaging features have not been extensively described. Three patients received 38.5 mg or 40 mg/m2 per day fludarabine in a 5-day intravenous infusion before bone marrow transplantation in treatment of hematopoietic malignancies. Several weeks later, each patient developed progressive neurologic decline, including retrogeniculate blindness, leading to coma and death. Brain MRI showed progressively enlarging but mild T2/FLAIR hyperintensities in the periventricular white matter. The lesions demonstrated restricted diffusion but did not enhance. Because the neurotoxicity of fludarabine appears long after exposure, neurologic decline in this setting is likely to be attributed to opportunistic disease. However, the imaging features are distinctive in their latency and in being mild relative to the profound clinical features. The safe dose of fludarabine in this context remains controversial.

Departments of Ophthalmology (MSL), Neurology (MSL), Neurosurgery (MSL), Neuroradiology (AMM, JRB), and Neuropathology (KS), University of Minnesota, Minneapolis, Minnesota.

This work was presented in part at the annual meeting of the Frank B. Walsh Society, Lake Tahoe, NV, February 2009.

This study was supported by an unrestricted grant from Research to Prevent Blindness (New York, NY) and the Minnesota Lions (to MSL).

Address correspondence to Michael S. Lee, MD, 420 Delaware Street SE, MMC 493, Minneapolis, MN 55455; E-mail:

© 2010 by North American Neuro-Ophthalmology Society