454 - Prolonged Neurologic Impairment Following High Dose Intrathecal Methotrexate, Inpatient Rehabilitation Outcome: A Case Report

Case Diagnosis: Methotrexate Induced Leukoencephalopathy

Case Description: A previously healthy and functionally independent 20 year old female diagnosed with T Cell Acute Lymphoblastic Leukemia (ALL) in remission, on interim maintenance therapy developed right hemiparesis and aphasia. Patient initially had an NIHSS score of 11, and physical exam showed 0/5 and 1/5 strength of the right upper and lower extremity respectively. Due to incongruent findings between CT and CTA, MRI displayed findings concerning for toxic-metabolic multifocal leukoencephalopathy. Patient previously on intrathecal (IT) methotrexate (15 mg/m2) had an increased dosage (150 mg/m2) 13 days prior to presentation. Patient was admitted to inpatient rehabilitation (IPR) for nine days, eight days after initial presentation. On admission to IPR patient had deficits of 3/5 right hip flexion and 4/5 right foot dorsiflexion, resolving but persistent aphasia, and abnormal cerebellar findings (ie proprioception, coordination). At time of discharge she was rated as independent in all categories except for ambulation (CGA) and problem solving/memory.

Discussions: The patient’s physical exam, laboratory values, and MRI findings were determined to be due to methotrexate toxicity causing Methotrexate-Induced Leukoencephalopathy. The literature associates leukoencephalopathy as a delayed complication of IT methotrexate usually presenting after six months to years later with cumulative IT dosing exceeding 140 mg. This patient began developing symptoms thirteen days after starting an IT methotrexate regimen surpassing the associated toxicity threshold. Clinical presentation was of ataxia and hemiparesis. Methotrexate neurotoxicity treatment is dextromethorphan 24 hours after symptoms onset and recovery expected by 13.9 hours. Patient received rescue treatment within 72 hours after presentation yet did not achieve recovery by the end of inpatient rehabilitation stay.

Conclusions: Early recognition/diagnosis of chemotherapy induced neurotoxicity is important for appropriate treatment. Deficits which impact patient functional status may persist despite appropriate rescue treatments.