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Abstract:
Ifosfamide-associated central nervous system toxicity has been reported in 5% to 30% of patients treated with ifosfamide. Its pattern is characterized by metabolic encephalopathy with confusion, blurred vision, mutism, auditory or visual paranoid hallucinations, seizures, and rarely coma. The biochemical cause of the neurotoxicity is not understood completely, but it is thought to result from an accumulation of drug metabolites with direct central nervous system effects. A case of ifosfamide neurotoxicity is reported that had unusual extrapyramidal features in a patient treated with a 5-day course of infused ifosfamide. Although usually spontaneously reversible with cessation of drug administration, ifosfamide neurotoxicity occasionally has been associated with prolonged psychopathologic sequelae. Death from irreversible encephalopathy has also been reported rarely. The authors believe that classic extrapyramidal symptoms should be considered to be a part of the neurotoxic profile of ifosfamide.
Insights
Ifosfamide can cause central nervous system toxicity, including encephalopathy and seizures, in 5% to 30% of patients. This case highlights unusual extrapyramidal symptoms as a potential feature of ifosfamide neurotoxicity.
Area of Science:
- Oncology
- Neuropharmacology
- Toxicology
Background:
- Ifosfamide is an alkylating agent used in cancer chemotherapy.
- Central nervous system (CNS) toxicity is a known, albeit variable, side effect of ifosfamide treatment, affecting 5% to 30% of patients.
- The exact mechanisms underlying ifosfamide-induced neurotoxicity are not fully elucidated but are hypothesized to involve toxic drug metabolites.
Observation:
- A patient receiving a 5-day course of infused ifosfamide developed neurotoxicity.
- The neurotoxicity presented with unusual extrapyramidal features, in addition to typical symptoms.
- Typical symptoms include metabolic encephalopathy, confusion, visual disturbances, mutism, hallucinations, seizures, and coma.
Findings:
- This case highlights that classic extrapyramidal symptoms can be part of the ifosfamide neurotoxic profile.
- The neurotoxicity is hypothesized to result from the accumulation of toxic drug metabolites affecting the CNS.
- While often reversible upon drug cessation, prolonged or severe neurotoxicity, including death, has been reported.
Implications:
- Clinicians should be vigilant for extrapyramidal symptoms as a potential manifestation of ifosfamide neurotoxicity.
- Recognition of a broader neurotoxic profile may aid in earlier diagnosis and management of ifosfamide-related CNS adverse events.
- Further research into the biochemical pathways of ifosfamide neurotoxicity is warranted to improve patient safety.