Intrathecal Methotrexate Toxicity Resulting in Brain Death due to Generalized Cerebral Edema Case Report

Abstract

Intrathecal methotrexate (IT MTX) resulting in severe adverse events including life-threatening cerebral edema is not well described. We report a rare case of death in a 37-year-old BRCA1+ woman with metastatic triple-negative breast cancer status post mastectomy following administration of IT MTX for leptomeningeal carcinomatosis. Within the 24 hours after intraoperative IT MTX delivery, she developed neurologically devastating diffuse cerebral edema leading to uncal and cerebellar tonsillar herniation. This case report highlights a rare but devastating side effect of IT MTX.

Keywords: breast cancer; carcinomatosis; case report; cerebral edema; intrathecal methotrexate.

Figure 1.

Post-gadolinium MRI of the brain and spine. A, Axial preoperative post-gadolinium T1 weighted brain MRI demonstrated widespread leptomeningeal enhancement along the cerebellum and right temporal cortex (B) with extension throughout the CNS involving the surface of the spinal cord and associated diffuse osseus metastatic disease (C).

Figure 2.

Non-contrast head CT Findings. A, Immediate postoperative non-contrast head CT with good placement of the Ommaya catheter. B, Repeat non-contrast head CT 19 hours after Ommaya placement and IT MTX administration.

Figure 3.

Autopsy and histopathological findings. , Ventral surface of the thoracic-lumbar spinal cord with dura opened longitudinally and pinned down. B, Close-up of hemorrhagic and partially necrotic deposits underneath arachnoid membrane. C, Hematoxylin and eosin (H&E) 100X magnification showing a stained section of cerebellum with extensive meningeal spread. D, 100X magnification H&E section of spinal cord (arrow indicates central canal) showing carcinoma extending through the ventral fissure.