Abstract
Abstract:Methotrexate (MTX) is an effective antimetabolite treatment for various oncological disorders including the central nervous system involvement (CNS) in widespread leukemia and CNS lymphoma. This form of treatment has a notable toxic effect on the nervous system, and the pediatric population seems to be more vulnerable to the neurologic toxicity of this drug. Though chronic leukoencephalopathy from an MTX regimen, especially when administered in conjunction with whole brain radiation, is well described, the acute manifestations are rare and not well understood. The diagnosis of acute focal symptoms from MTX treatment is especially difficult in patients who receive chemotherapy for neoplastic disorders and who may have many reasons for CNS involvement in general and parenchymal involvement in particular. We report the unusual clinical and neuro-imaging findings in a teenager with acute focal symptoms after MTX treatment for acute lymphoblastic leukemia.
This content is limited to qualifying members.
If you have an existing account please login now to access this article or view purchase options.
Create a free account, then purchase this article to download or access it online for 24 hours.
Create a free account, then purchase a subscription to get complete access to all articles for a full year.
References
References1. Ravindranath Y. Recent advances in pediatric acute lymphoblastic and myeloid leukemia. Curr Opin Oncol 2003;15:23–35.RavindranathYRecent advances in pediatric acute lymphoblastic and myeloid leukemia.Curr Opin Oncol20031523-352. Atra A, Pinkerton CR, Bouffet E, et al; United Kingdom Children Cancer Study Group/Non-Hodgkin Lymphoma Group. Acute neurotoxicity in children with advanced stage B-non-Hodgkin’s lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols. Eur J Cancer 2004;40:1346–1350.AtraA]]PinkertonCR]]BouffetE&etal;United Kingdom Children Cancer Study GroupNon-Hodgkin Lymphoma GroupAcute neurotoxicity in children with advanced stage B-non-Hodgkin’s lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols.Eur J Cancer2004401346-13503. Mahoney DH Jr, Shuster JJ, Nitschke R, et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy—a Pediatric Oncology Group study. J Clin Oncol 1998;16:1712–1722.MahoneyDHJr]]ShusterJJ]]NitschkeR&etal;Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy—a Pediatric Oncology Group study.J Clin Oncol1998161712-17224. Filley CM, Kleinschmidt-DeMasters BK. Toxic leukoencephalopathy. N Engl J Med 2001;345:425–432.FilleyCM]]Kleinschmidt-DeMastersBKToxic leukoencephalopathy.N Engl J Med2001345425-4325. Antunes NL, Souweidane MM, Lis E, et al. Methotrexate leukoencephalopathy presenting as Klüver-Bucy syndrome and uncinate seizures. Pediatr Neurol 2002;26:305–308.AntunesNL]]SouweidaneMM]]LisE&etal;Methotrexate leukoencephalopathy presenting as Klüver-Bucy syndrome and uncinate seizures.Pediatr Neurol200226305-3086. Rollins N, Winick N, Bash R, et al. Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome. AJNR Am J Neuroradiol 2004;25:1688–1695.RollinsN]]WinickN]]BashR&etal;Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome.AJNR Am J Neuroradiol2004251688-16957. Shuper A, Stark B, Kornreich L, et al. Methotrexate treatment protocols and the central nervous system: significant cure with significant neurotoxicity. J Child Neurol 2000;15:573–580.ShuperA]]StarkB]]KornreichL&etal;Methotrexate treatment protocols and the central nervous system: significant cure with significant neurotoxicity.J Child Neurol200015573-5808. Shuper A, Stark B, Kornreich L, et al. Methotrexate-related neurotoxicity in the treatment of childhood acute lymphoblastic leukemia. Isr Med Assoc J 2002;4:1050–1053.ShuperA]]StarkB]]KornreichL&etal;Methotrexate-related neurotoxicity in the treatment of childhood acute lymphoblastic leukemia.Isr Med Assoc J200241050-10539. Kishi Y, Miyakoshi S, Kami M, et al; Tokyo Stem Cell Transplantation Consortium. Early central nervous system complications after reduced-intensity stem cell transplantation. Biol Blood Marrow Transplant 2004;10:561–568.KishiY]]MiyakoshiS]]KamiM&etal;Tokyo Stem Cell Transplantation ConsortiumEarly central nervous system complications after reduced-intensity stem cell transplantation.Biol Blood Marrow Transplant200410561-56810. Orbach D, Brisse H, Doz F. [Central neurological manifestations during chemotherapy in children]. Arch Pediatr 2003;10:533–539 [in French].11. Rzeski W, Pruskil S, Macke A, et al. Anticancer agents are potent neurotoxins in vitro and in vivo. Ann Neurol 2004;56:351–360.RzeskiW]]PruskilS]]MackeA&etal;Anticancer agents are potent neurotoxins in vitro and in vivo.Ann Neurol200456351-36012. Linnebank M, Pels H, Kleczar N, et al. MTX-induced white matter changes are associated with polymorphisms of methionine metabolism. Neurology 2005;64:912–913.LinnebankM]]PelsH]]KleczarN&etal;MTX-induced white matter changes are associated with polymorphisms of methionine metabolism.Neurology200564912-91313. Winick NJ, Bowman WP, Kamen BA, et al. Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. J Natl Cancer Inst 1992;84:252–256.WinickNJ]]BowmanWP]]KamenBA&etal;Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia.J Natl Cancer Inst199284252-25614. Asato R, Akiyama Y, Ito M, et al. Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate. Cancer 1992;70:1997–2004.AsatoR]]AkiyamaY]]ItoM&etal;Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate.Cancer1992701997-200415. Brock S, Jennings HR. Fatal acute encephalomyelitis after a single dose of intrathecal methotrexate. Pharmacotherapy 2004;24:673–676.BrockS]]JenningsHRFatal acute encephalomyelitis after a single dose of intrathecal methotrexate.Pharmacotherapy200424673-67616. Rubnitz JE, Relling MV, Harrison PL, et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. Leukemia 1998;12:1176–1181.RubnitzJE]]RellingMV]]HarrisonPL&etal;Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia.Leukemia1998121176-118117. Lai R, Abrey LE, Rosenblum MK, et al. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology 2004;62:451–456.LaiR]]AbreyLE]]RosenblumMK&etal;Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study.Neurology200462451-45618. Quinn CT, Griener JC, Bottiglieri T, et al. Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid. J Pediatr Hematol Oncol 2004;26:386–388.QuinnCT]]GrienerJC]]BottiglieriT&etal;Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid.J Pediatr Hematol Oncol200426386-38819. Quinn CT, Griener JC, Bottiglieri T, et al. Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. J Clin Oncol 1997;15:2800–2806.QuinnCT]]GrienerJC]]BottiglieriT&etal;Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer.J Clin Oncol1997152800-280620. Ebner F, Ranner G, Slavc I, et al. MR findings in methotrexate-induced CNS abnormalities. AJR Am J Roentgenol 1989;153:1283–1288.EbnerF]]RannerG]]SlavcI&etal;MR findings in methotrexate-induced CNS abnormalities.AJR Am J Roentgenol19891531283-128821. Sandoval C, Kutscher M, Jayabose S, et al. Neurotoxicity of intrathecal methotrexate: MR imaging findings. AJNR Am J Neuroradiol 2003;24:1887–1890.SandovalC]]KutscherM]]JayaboseS&etal;Neurotoxicity of intrathecal methotrexate: MR imaging findings.AJNR Am J Neuroradiol2003241887-189022. Davidson A, Payne G, Leach MO, et al. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer. Med Pediatr Oncol 2000;35:28–34.DavidsonA]]PayneG]]LeachMO&etal;Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high-dose methotrexate treatment for childhood cancer.Med Pediatr Oncol20003528-3423. Cohen IJ. Defining the appropriate dosage of folinic acid after high-dose methotrexate for childhood acute lymphatic leukemia that will prevent neurotoxicity without rescuing malignant cells in the central nervous system. J Pediatr Hematol Oncol 2004;26:156–163.CohenIJDefining the appropriate dosage of folinic acid after high-dose methotrexate for childhood acute lymphatic leukemia that will prevent neurotoxicity without rescuing malignant cells in the central nervous system.J Pediatr Hematol Oncol200426156-16324. Jaksic W, Veljkovic D, Pozza C, et al. Methotrexate-induced leukoencephalopathy reversed by aminophylline and high-dose folinic acid. Acta Haematol 2004;111:230–232.JaksicW]]VeljkovicD]]PozzaC&etal;Methotrexate-induced leukoencephalopathy reversed by aminophylline and high-dose folinic acid.Acta Haematol2004111230-23225. Murphy AN, Fiskum G, Beal MF. Mitochondria in neurodegeneration: bioenergetic function in cell life and death. J Cereb Blood Flow Metab 1999;19:231–245.MurphyAN]]FiskumG]]BealMFMitochondria in neurodegeneration: bioenergetic function in cell life and death.J Cereb Blood Flow Metab199919231-245
