(667) Severe Methotrexate-Induced Neurotoxicity in a Hispanic Adolescent Girl With B-ALL

Introduction: Methotrexate (MTX) is commonly used to treat pediatric acute lymphoblastic leukemia (ALL). Central nervous system (CNS) neurotoxicity is a known complication with incidence ranging from 3-7%. Typically, patients develop symptoms within 5 to 14 days of high dose intravenous or intrathecal (IT) MTX administration. Presentation may include altered mental status, stroke-like episodes, and seizures. In most cases, symptoms resolve within 2 weeks. Below, we describe an adolescent patient with atypical, severe, and prolonged MTX-induced CNS neurotoxicity.

Description: A 13-year-old Hispanic female with high-risk B-ALL presented 5 days after IT MTX with progressive encephalopathy and quadriparesis. At presentation, she was awake but unresponsive and had no purposeful movements. Brain MRI was consistent with severe MTX leukoencephalopathy. She received dextromethorphan, aminophylline, and leucovorin rescue with no improvement. She subsequently developed episodic agitation with tachypnea, tachycardia, grunting, and hypertonia. Dexmedetomidine was used to manage these episodes while maintaining a natural airway along with enteral clonidine, methadone, and diazepam. Despite aggressive treatment of the underlying condition and targeted symptom control, she had minimal improvement in symptoms after 2 weeks. Given her prolonged symptoms, she had a broad work up to rule out other etiologies including infection, seizures, and autoimmune disease. With time and optimizing enteral medications, dexmedetomidine was discontinued, allowing for transfer out of the ICU on hospital day (HD) 21 with little change in her neurologic exam. On HD 38, she transferred to the inpatient rehabilitation service. Upon discharge on HD 87, she was able to say some words, required maximal assistance for most activities of daily living, and remained non-ambulatory.

Discussion: This case highlights important clinical considerations. The use of dexmedetomidine over other agents mitigated agitation without decreasing respiratory drive, preventing the need for intubation and possible ICU morbidities, which are implicated in the morbidity of patients with severe MTX-induced neurotoxicity. This case also contributes to growing literature that suggests a potential increased risk of MTX-induced neurotoxicity in Hispanic patients.