To present a case of ifosfamide-induced neurotoxicity presenting as new onset seizures with transient bilateral putaminal MRI changes and recognize early presentation of neurotoxic agents.

Ifosfamide is an alkylating chemotherapeutic agent that is associated with neurotoxicity in a subset of patients. Presentations can vary from mild confusion to seizures and coma. Early identification of these signs is important to aid prompt management.

A 61-year-old female with a history of pleomorphic sarcoma with pulmonary metastases received her first dose of ifosfamide-containing chemotherapy. The patient had a first-time generalized tonic-clonic seizure at the infusion center shortly after infusion, followed by hypoxia and hypertensive crisis. Upon arrival at the hospital, she was intubated for hypercapnic respiratory failure. Brain MRI revealed bilateral putaminal hyperintensity on diffusion-weighted imaging (DWI) with concomitant hypointensity on apparent diffusion coefficient (ADC), which was initially concerning for acute ischemic stroke, and right mesial temporal sclerosis. EEG revealed diffuse background slowing and right temporal sharp waves. She was treated with Mesna and methylene blue for suspicion of ifosfamide toxicity.  Repeat brain imaging 6 days after initial brain MRI revealed resolution of bilateral putaminal diffusion restriction, consistent with transient chemotherapy-induced toxic encephalopathy. Early suspicion of ifosfamide toxicity resulted in early treatment with reversal agents and supportive measures including anti-seizure medications with subsequent improvement in her neurological function.

This case highlights a rare but serious neurotoxic complication of ifosfamide chemotherapy. It emphasizes that transient DWI changes in bilateral putamen may initially be misleading for a cerebrovascular process. Hence, repeat imaging is imperative to show resolution of DWI changes.  It also underscores the importance of clinicians being aware of ifosfamide’s neurotoxic potential to reduce seizure thresholds in patients with structural abnormalities such as mesial temporal sclerosis.