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Vascular Neurotoxicity Following Chemotherapy with Cisplatin, Ifosfamide, and Etoposide

Research Associate and Fellow of the Wilmot Cancer Foundation, Department of Biomedical Genetics, University of Rochester, Rochester, NY; Resident in Neurology, Department of Neurology, University of Regensburg, Regensburg, Germany

Jörg Marienhagen, MD

Assistant Professor, Department of Nuclear Medicine, University of Regensburg

Berthold Schalke, MD

Professor of Neurology, Department of Neurology, University of Regensburg

Ulrich Bogdahn, MD

Professor of Neurology and Chair, Department of Neurology, University of Regensburg

Felix Schlachetzki, MD

Research Associate, Department of Medicine, University of California at Los Angeles, Los Angeles, CA; Resident in Neurology, Department of Neurology, University of Regensburg

Reprints: Jörg Dietrich MD, Department of Biomedical Genetics, University of Rochester, 601 Elmwood Ave., Box 633, Rochester, NY 14642-8609, fax 585/273-1450, joergD{at}URMC.rochester.edu

OBJECTIVE: To report a case of acute central nervous system (CNS) toxicity with multiple hemorrhages restricted to the corpus callosum associated with combination therapy of cisplatin, ifosfamide, and etoposide.

CASE SUMMARY: A 38-year-old white man with a testicular germ cell tumor received a cisplatin-based chemotherapy consisting of cisplatin 45 mg (20 mg/m²), etoposide 570 mg (250 mg/m²), and ifosfamide 4600 mg (2000 mg/m²) given on 5 consecutive days during each course. After the first course of chemotherapy, the patient appeared to be neuropsychologically impaired with episodes of decreased alertness and features of a depressive syndrome. He became severely diminished in mental function, orientation, and psychomotor activity after a second course of treatment. In addition, he showed transient urinary incontinence. Motor and sensory deficits could not be detected. Magnetic resonance imaging demonstrated multiple hemorrhages restricted to the corpus callosum. An objective causality assessment revealed that an adverse drug reaction was probable.

DISCUSSION: Neurotoxicity has been associated with the administration of various antineoplastic agents. In particular, cisplatin and ifosfamide can cause both acute and delayed CNS toxicity. While ifosfamide neurotoxicity has been predominantly associated with neuropsychological impairment without evidence of structural abnormalities in neuroimaging studies, cisplatin has been shown to cause cerebrovascular complications. Various pathophysiologic conditions may contribute to these complications including thrombosis secondary to vascular endothelial injury or thromboembolic events. To our knowledge, as of December 2, 2003, vascular lesions restricted to the corpus callosum have not been reported as a complication of cisplatin- or ifosfamide-based chemotherapy.

CONCLUSIONS: Clinicians should be aware of the potential neurovascular adverse effects of cisplatin-based protocols. This is especially true in patients with subtle neurologic or neuropsychological symptoms. Chemotherapy-induced neurotoxicity should be considered in the differential diagnosis.

Key Words: central nervous system toxicity, cisplatin, corpus callosum, ifosfamide

Published Online, December 15, 2003. www.theannals.com, DOI 10.1345/aph.1D106

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