Metabolite Levels Measured Using Magnetic Resonance Spectroscopy in Pediatric Methotrexate-Induced...

Area of Science:

• Pediatric Neurology
• Neuro-oncology
• Radiology

Background:

• Methotrexate (MTX) is a chemotherapy agent used in treating pediatric acute lymphoblastic leukemia (ALL).
• MTX can cause a serious neurological side effect known as leukoencephalopathy.
• Magnetic resonance spectroscopy (MRS) offers a noninvasive method to detect metabolic changes indicative of neurotoxicity.

Purpose of the Study:

• To investigate the diagnostic and prognostic utility of MRS-derived N-acetylaspartate and N-acetylaspartylglutamate (tNAA) levels.
• To assess the role of tNAA in MTX-induced leukoencephalopathy in pediatric ALL patients.

Main Methods:

• Retrospective analysis of 89 pediatric ALL patients (2009-2022).
• Examination of 261 MRS datasets focusing on centrum semiovale metabolic changes.
• Mixed logistic regression to evaluate tNAA association with leukoencephalopathy and clinical recovery.

Main Results:

• Patients with leukoencephalopathy exhibited significantly lower tNAA levels compared to controls.
• A decrease in pretreatment tNAA levels by 1.0-point correlated with a 3.22-fold increased odds of developing leukoencephalopathy.
• Increasing tNAA levels over time showed a significant correlation with clinical improvement.

Conclusions:

• MRS-derived tNAA levels show potential as a biomarker for diagnosing and monitoring MTX-induced leukoencephalopathy.
• Integrating MRS into clinical practice may enable earlier intervention and improved treatment strategies.
• Further prospective studies are needed to validate these findings and their impact on patient outcomes.