Journal of Clinical Pediatrics >
Dextromethorphan in the treatment of acute encephalopathy induced by methotrexate: a case report
Received date: 2024-05-29
Accepted date: 2024-08-30
Online published: 2025-02-12
Objective To improve the understanding of methotrexate-induced acute encephalopathy and explore the efficacy and safety of dextromethorphan in the treatment of methotrexate-induced central neurotoxicity. Methods A retrospective analysis was performed on a patient in our hospital with acute encephalopathy caused by high-dose intravenous methotrexate combined with intrathecal methotrexate. Additionally, the published literature was reviewed to evaluate the potential efficacy and safety of dextromethorphan. Results The child was diagnosed with stage IV Burkitt lymphoma and was treated with chemotherapy in the China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) C group. On the day following the initial administration of methotrexate, the patient exhibited clinical symptoms, including headache and visual impairment, and multiple patchy T2WI hypersignal images in the bilateral occipital cortex and bilateral cerebellar hemispheres were observed on head MRI. After oral administration of dextromethorphan, there was a gradual recovery of binocular vision and a reduction in the clinical symptoms. Conclusion In the case of acute encephalopathy induced by methotrexate, early treatment with dextromethorphan may have a therapeutic effect on severe neurotoxicity induced by methotrexate.
Key words： methotrexate; neurotoxicity; dextromethorphan
LUO Wentao , CHEN Jihui , ZHANG Xin , YU Juanjuan . Dextromethorphan in the treatment of acute encephalopathy induced by methotrexate: a case report[J]. Journal of Clinical Pediatrics, 2025 , 43(2) : 141 -146 . DOI: 10.12372/jcp.2025.24e0546
| [1] | Panicker VV, Radhakrishnan SE, Kuruttukulam GV, et al. Methotrexate-induced leukoencephalopathy as a clinical and radiological mimicker of acute ischemic stroke leading to thrombolysis[J]. Cureus, 2024, 16(1): e51542. |
| [2] | Inaba H, Khan RB, Laningham FH, et al. Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer[J]. Ann Oncol, 2008, 19(1): 178-184. |
| [3] | Rubnitz J, Relling M, Harrison P, et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia[J]. Leukemia, 1998, 12(8): 1176-1181. |
| [4] | Walker RW, Allen JC, Rosen G, et al. Transient cerebral dysfunction secondary to high-dose methotrexate[J]. J Clin Oncol, 1986, 4(12): 1845-1850. |
| [5] | Vezmar S, Schüsseler P, Becker A, et al. Methotrexate‐associated alterations of the folate and methyl‐transfer pathway in the csf of ALL patients with and without symptoms of neurotoxicity[J]. Pediatr Blood Cancer, 2008, 52(1): 26-32. |
| [6] | Kishi S, Griener J, Cheng C, et al. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia[J]. J Clin Oncol, 2003, 21(16): 3084-3091. |
| [7] | Janeway KA, Grier HE. Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects[J]. Lancet Oncol, 2010, 11(7): 670-678. |
| [8] | Ziemińska E, Stafiej A, ?azarewicz JW. Role of group I metabotropic glutamate receptors and NMDA receptors in homocysteine-evoked acute neurodegeneration of cultured cerebellar granule neurones[J]. Neurochem Int, 2003, 43(4-5): 481-492. |
| [9] | Poddar R. Hyperhomocysteinemia is an emerging comorbidity in ischemic stroke[J]. Exp Neurol, 2021, 336: 113541. |
| [10] | Refsum H, Ueland PM, Kvinnsland S. Acute and long-term effects of high-dose methotrexate treatment on homocysteine in plasma and urine[J]. Cancer Res, 1986, 46(10): 5385-5391. |
| [11] | Goldin A, Venditti JM, Kline I, et al. Eradication of leukaemic cells (l1210) by methotrexate and methotrexate plus citrovorum factor[J]. Nature, 1966, 212(5070): 1548-1550. |
| [12] | Ackland SP, Schilsky RL. High-dose methotrexate: a critical reappraisal[J]. J Clin Oncol, 1987, 5(12): 2017-2031. |
| [13] | Afshar M, Birnbaum D, Golden C. Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity[J]. Pediatr Neurol, 2014, 50(6): 625-629. |
| [14] | Silva AR, Dinis-Oliveira RJ. Pharmacokinetics and pharmacodynamics of dextromethorphan: Clinical and forensic aspects[J]. Drug Metab Rev, 2020, 52(2): 258-282. |
| [15] | Nguyen L, Thomas KL, Lucke-Wold BP, et al. Dextro-methorphan: An update on its utility for neurological and neuropsychiatric disorders[J]. Pharmacol Ther, 2016, 159: 1-22. |
| [16] | Vijayanathan V, Gulinello M, Ali N, et al. Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated csf concentrations of excitotoxic glutamate analogs and can be reversed by an nmda antagonist[J]. Behav Brain Res, 2011, 225(2): 491-497. |
| [17] | Drachtman RA, Cole PD, Golden CB, et al. Dextro-methorphan is effective in the treatment of subacute methotrexate neurotoxicity[J]. Pediatr Hematol Oncol, 2002, 19(5): 319-327. |
| [18] | Bettachi CJ, Kamen BA, Cush JJ. Post-methotrexate (MTX) CNS toxicity: symptom reduction with dextromethorphan[C]. Arthritis Rheum, 1999. |
| [19] | Rogers P, Pan WJ, Drachtman RA, et al. A stroke mimic: methotrexate-induced neurotoxicity in the emergency department[J]. J Emerg Med, 2017, 52(4): 559-561. |
| [20] | Schmidt LS, Kj?r TW, Schmiegelow K, et al. Eeg with extreme delta brush in young female with methotrexate neurotoxicity supports nmda receptor involvement[J]. Eur J Paediatr Neurol, 2017, 21(5): 795-797. |
| [21] | Giordano L, Akinyede O, Bhatt N, et al. Methotrexate-induced neurotoxicity in hispanic adolescents with high-risk acute leukemia—a case series[J]. J Adolesc Young Adult Oncol, 2017, 6(3): 494-498. |
| [22] | Coker SA, Pastel DA, Davis MC, et al. Methotrexate encephalopathy: two cases in adult cancer patients, who recovered with pathophysiologically based therapy[J]. SAGE Open Med Case Rep, 2017, 5: 2050313X1770687. |
| [23] | Rubin MF, Kuhn AK. Management of methotrexate‐induced neurotoxicity with aminophylline plus dextro-methorphan in a pediatric patient with pineoblastoma[J]. Pediatr Blood Cancer, 2020, 67(12): e28515. |
| [24] | Mateos MK, Marshall GM, Barbaro PM, et al. Metho-trexate-related central neurotoxicity: Clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia[J]. Haematologica, 2022, 107(3): 635-643. |
| [25] | Fustino NJ, Juhl K, Leister J. Dextromethorphan administration on day 0 and day 7 for secondary prevention of methotrexate-induced neurotoxicity in childhood acute lymphoblastic leukemia: A retrospective case series[J]. J Pediatr Hematol Oncol, 2021, 43(2): e284-e287. |
| [26] | Spangler DC, Loyd CM, Skor EE. Dextromethorphan: a case study on addressing abuse of a safe and effective drug[J]. Subst Abuse Treat Prev Policy, 2016, 11(1): 22. |
/
| 〈 |
|
〉 |
