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Clinical and EEG Characteristics of Ifosfamide-Related Encephalopathy

Gusdon, Aaron M.*,†; Malani, Rachna*; Chen, Xi*

Journal of Clinical Neurophysiology: March 2019 - Volume 36 - Issue 2 - p 150–154
doi: 10.1097/WNP.0000000000000539
Original Research

Purpose: Ifosfamide can lead to a syndrome of central nervous system toxicity. Here, we investigate the clinical and EEG characteristics of patients with ifosfamide-related encephalopathy.

Methods: Retrospective data were collected on patients from Memorial Sloan Kettering Cancer Center, who developed encephalopathy associated with ifosfamide between 2007 and 2017. Patients who had an EEG performed were included. Clinical and laboratory data were retrospectively collected. Each EEG recording was reviewed and compared with the originally documented EEG report.

Results: Sixteen patients with ifosfamide-related encephalopathy were included, with primary tumors consisting of lymphoma (N = 9), sarcoma (N = 4), poorly differentiated ovarian cancer (N = 1), neuroblastoma (N = 1), and papillary serous adenocarcinoma (N = 1). Laboratory results ruled out other etiologies of encephalopathy. Generalized periodic discharges with or without triphasic morphology were seen most commonly (N = 9), with a distinct pattern of interspersed intermittent background attenuation seen in five patients. Background slowing and intermittent rhythmic delta activity (N = 4), bursts of bilateral synchronized delta activity (N = 2), and frontal predominant intermittent delta activity (N = 1) were also seen. One patient demonstrated a pattern consistent with nonconvulsive status epilepticus. Although most patients experienced resolution of symptoms, those who died demonstrated a variety of EEG abnormalities. Abnormal movements were common, with six patients demonstrating characteristic orofacial myoclonus.

Conclusions: Ifosfamide-related encephalopathy commonly results in a distinct pattern of generalized periodic discharges admixed with intermittent background attenuation on EEG. Abnormal movements, in particular orofacial myoclonus, are also common. Recognizing these clinical and EEG features might lead to early detection of ifosfamide-related encephalopathy.

*Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, U.S.A.; and

Division of Neurocritical Care, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.

Address correspondence and reprint requests to Xi Chen, MD, PhD, Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, U.S.A.; e-mail:

A.M. Gusdon received support from the National Natural Science Foundation of China (grant number 81550110260). The remaining authors have no funding or conflicts of interest to disclose.

A. M. Gusdon and R. Malani contributed equally to the manuscript.

© 2019 by the American Clinical Neurophysiology Society