title: Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.
abstract: BACKGROUND
  The pathogenesis of methotrexate central nervous system toxicity is multifactorial, but it is likely related to central nervous system folate homeostasis. The use of folinate rescue has been described to decrease toxicity in patients who had received intrathecal methotrexate. It has also been described in previous studies that there is an elevated level of homocysteine in plasma and cerebrospinal fluid of patients who had received intrathecal methotrexate. Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor antagonist, has been used in the treatment of sudden onset of neurological dysfunction associated with methotrexate toxicity. It remains unclear whether the dextromethorphan impacted the speed of recovery, and its use remains controversial. This study reviews the use of dextromethorphan in the setting of subacute methotrexate central nervous system toxicity.
  
  
  METHODS
  Charts of 18 patients who had sudden onset of neurological impairments after receiving methotrexate and were treated with dextromethorphan were reviewed.
  
  
  RESULTS
  The use of dextromethorphan in most of our patients resulted in symptomatic improvement. In this patient population, earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity.
  
  
  CONCLUSIONS
  Our study provides support for the use of dextromethorphan in patients with subacute methotrexate central nervous system toxicity.
authors.affiliation: Department of Pediatrics, Children's Hospital & Research Center Oakland, Oakland California. Electronic address: mamaryamafshar@gmail.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Department of Pediatric Neurology, Children's Hospital & Research Center Oakland, Oakland California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Department of Pediatric Hematology/Oncology, Children's Hospital & Research Center Oakland, Oakland California.
authors.forename: Carla
authors.initials: C
authors.lastname: Golden
mesh_terms: D002491:Central Nervous System Agents / Q000627:therapeutic use*; D002648:Child; D003915:Dextromethorphan / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D002491:Central Nervous System Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D008727:Methotrexate
keywords: NMDA receptor; dextromethorphan; homocysteine; methotrexate CNS toxicity