Ifosfamide-induced extrapyramidal neurotoxicity with COVID-19

Ifosfamide, an analog of cyclophosphamide, is commonly used as a chemotherapeutic agent to treat sarcomas and solid tumors. However, neurotoxicity is a rare side effect of this drug. When present, the symptoms range from confusion, agitation, and delirium in mild cases to mutism, visual blurring, hallucinations, seizures, stupor, and even coma in extreme cases. Within this spectrum, extrapyramidal symptoms are extremely rare, and when present, may not revert with drug discontinuation. Sequelae may occasionally persist even after discontinuation of the drug. Our case illustrates a rare occurrence of ifosfamide-induced extrapyramidal neurotoxicity in a patient with metastatic phyllodes tumor of the breast and concomitant COVID-19 illness. Ifosfamide-induced extrapyramidal neurotoxicity is a clinical diagnosis of exclusion and requires ruling out of other possible causes. The diagnosis is supported by a temporal correlation with drug administration, presence of risk factors, and improvement after infusion cessation, along with normal brain imaging.