Neurotoxicity due to CNS therapy for leukemia

Area of Science:

• Neuro-oncology
• Pediatric oncology
• Neuropharmacology

Background:

• Central nervous system (CNS) radiotherapy and intrathecal chemotherapy are associated with neurological toxicities.
• Manifestations range from mild encephalopathy and somnolence to severe neurological deficits.
• Distinguishing the cause of CNS symptoms in pediatric leukemia patients receiving intensive treatment is complex.

Purpose of the Study:

• To review the spectrum of neurotoxicity associated with CNS radiotherapy and intrathecal chemotherapy.
• To discuss potential pathogenetic mechanisms of methotrexate neurotoxicity.
• To highlight the challenges in diagnosing CNS complications in pediatric leukemia.

Main Methods:

• Literature review of CNS radiotherapy and intrathecal chemotherapy-induced neurotoxicity.
• Analysis of reported neurological complications in pediatric leukemia patients.
• Discussion of proposed mechanisms for methotrexate neurotoxicity and leukoencephalopathy.

Main Results:

• Cranial radiotherapy can cause mild encephalopathy and, rarely, progressive encephalopathy.
• Intrathecal methotrexate may lead to meningeal irritation, weakness, paralysis, and severe encephalopathy.
• Leukoencephalopathy has been observed post-therapy, potentially due to radiotherapy altering the blood-brain barrier.

Conclusions:

• Neurotoxicity is a significant concern in pediatric patients treated with CNS-directed therapies for leukemia.
• Understanding the pathogenesis of methotrexate neurotoxicity is crucial for managing these complications.
• Further research is needed to elucidate the precise mechanisms and improve patient outcomes.