Metabolite Levels Measured Using Magnetic Resonance Spectroscopy in Pediatric Methotrexate-Induced Leukoencephalopathy.
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BACKGROUND: Methotrexate (MTX)-induced leukoencephalopathy is a significant neurological complication in pediatric acute lymphoblastic leukemia (ALL) treatment. Magnetic resonance spectroscopy (MRS) is a noninvasive method to assess metabolic changes associated with neurotoxicity. This study aimed to evaluate the diagnostic and prognostic value of MRS-derived metabolite levels, particularly N-acetylaspartate and N-acetylaspartylglutamate (tNAA), in MTX-induced leukoencephalopathy. PROCEDURE: We retrospectively analyzed 89 pediatric patients with ALL who underwent brain magnetic resonance imaging (MRI) and MRS at Kanagawa Children's Medical Center between 2009 and 2022. A total of 261 MRS datasets were examined, focusing on metabolic changes in the centrum semiovale. Using mixed logistic regression, we evaluated the association between tNAA levels and leukoencephalopathy onset, as well as their correlation with clinical recovery after MTX discontinuation. RESULTS: Patients with leukoencephalopathy had significantly lower tNAA levels than those of controls. A predictive model indicated that a 1.0-point decrease in pretreatment tNAA levels was associated with an approximately 3.22-fold increase in the odds of developing MTX-induced leukoencephalopathy. Furthermore, increasing tNAA levels over time were significantly correlated with clinical improvement. CONCLUSION: This study suggests that tNAA levels measured using MRS may serve as a potential biomarker for diagnosing and monitoring MTX-induced leukoencephalopathy. Integrating MRS into clinical assessments may represent a promising future approach to facilitate earlier intervention, inform treatment strategies, and potentially improve patient outcomes, pending validation by future prospective studies. These findings highlight the importance of MRS in the real-time evaluation of disease progression and therapeutic responses in pediatric patients undergoing MTX treatment.