A Case of Methotrexate Neurotoxicity Presented as Status Epilepticus, Encephalopathy, and High Fever

Abstract

High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms. We present a case of a 14-year-old boy with a recent diagnosis of osteosarcoma who presented to the emergency department with status epilepticus, altered mental status, and very high fever secondary to methotrexate neurotoxicity. We review current literature and discuss some controversies related to this state. We also describe high fever as one of the possible symptoms associated with this condition and suggest using specific magnetic resonance imaging sequence to uncover abnormal findings related to this state. Since high-dose methotrexate is not a rare treatment in this era, we believe that in addition to oncologists, emergency department and intensive care providers should be aware of the potential role of methotrexate in causing significant neurotoxicity and include it in the differential diagnosis when treating a patient presenting with new neurological symptoms in the setting of recent high-dose methotrexate treatment.

Suicide attempt induced by drug‐induced leukoencephalopathy: A case report

“… 5 In acute cases where encephalopathy occurs within approximately 2 weeks of administration, withdrawal of the drug may result in significant improvement in symptoms within 1 week of symptom onset, whereas in slow‐onset cases, symptoms often persist. 5 , 6 In this case, encephalopathy symptoms appeared at the end of the fourth course, indicating the slow onset of symptoms, and the detection of symptoms was delayed due to the presence of aphasia.…”

“…In some patients, encephalopathy symptoms appeared immediately after methotrexate was administered, while in other cases, encephalopathy symptoms appeared approximately 6 months after methotrexate was administered 5 . In acute cases where encephalopathy occurs within approximately 2 weeks of administration, withdrawal of the drug may result in significant improvement in symptoms within 1 week of symptom onset, whereas in slow‐onset cases, symptoms often persist 5,6 . In this case, encephalopathy symptoms appeared at the end of the fourth course, indicating the slow onset of symptoms, and the detection of symptoms was delayed due to the presence of aphasia.…”

Methotrexate-Induced Stroke-Like Encephalopathy: Beware the Stroke Mimic

“…Multiple underlying mechanisms are possibly involved, including (i) a direct toxicity of homocysteine on the vascular endothelium, (ii) an increased excitatory effects on N-methyl-D-aspartate receptors by homocysteine-derived metabolites, (iii) alterations of adenosine metabolism, (iiii) a chronic folate depletion in brain tissue, and (iiiii) a direct neuronal damage by MTX [5]. In most reported cases, re-exposure to intrathecal MTX administration was not associated with recurrence of neurotoxicity, but any treatment decision must include a careful weighing of potential risks of relapse against anti-tumor benefits [1,2].…”

Management of methotrexate‐induced neurotoxicity with aminophylline plus dextromethorphan in a pediatric patient with pineoblastoma

“…1,3,4,[7][8][9][10]16 A 17-year-old, 49.8-kg female with pineoblastoma was admitted for date, no reports have described the use of aminophylline with adjunctive dextromethorphan for MTX-induced neurotoxicity in a patient witha CNS malignancy. 1,2,[8][9][10]18 We attempt to provide insight into the frequency, duration, and monitoring of aminophylline for the management of MTXinduced neurotoxicity. A previous report of aminophylline 100 mg IV every 6 h described improvement with near complete recovery by 72 h; however, aminophylline was discontinued after 5 days due to persistent tachycardia and agitation.…”

“…This report describes our experience using IV aminophylline plus enteral dextromethorphan for management of MTX‐induced neurotoxicity in a pediatric patient with pineoblastoma. Existing reports describing aminophylline for MTX‐induced neurotoxicity are in patients with either hematologic malignancies or osteosarcoma; to date, no reports have described the use of aminophylline with adjunctive dextromethorphan for MTX‐induced neurotoxicity in a patient witha CNS malignancy 1,2,8‐10,18 …”