Vascular Neurotoxicity Following Chemotherapy with Cisplatin, Ifosfamide, and Etoposide

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Abstract
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/m 2 ), etoposide 570 mg (250 mg/m 2 ), and ifosfamide 4600 mg (2000 mg/m 2 ) 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.