title: A novel mechanism of toxic injury to the Papez circuit from chemotherapy.
abstract: Toxic effects of chemotherapy delivered via Ommaya reservoir include pericatheter necrosis and toxic leukoencephalopathy. Imaging evidence of toxicity is often asymptomatic, but can be clinically consequential. A young patient, treated for cerebrospinal fluid relapse of acute lymphoblastic leukemia with methotrexate and cytarabine via Ommaya reservoir, presented with acute deterioration of short-term memory. MRI demonstrated extra-ventricular Ommaya catheter position and typical methotrexate-induced changes in the deep white matter, but also signal alteration in the forniceal columns and mammillary bodies, components of the Papez circuit. This case presents a novel mechanism of chemotherapy-induced neurotoxicity associated with extra-ventricular Ommaya catheter position. Specifically, the clinical and imaging findings suggest that extra-ventricular Ommaya catheter position may lead to a direct methotrexate-induced toxicity to the Papez circuit. This provides further clinical evidence of the function of the circuit. The possibility that this patient received a supratherapeutic dose of methotrexate may explain why this presentation with profound memory impairment is not more common. However, this case also provides a potential explanation for patients who receive standard dose chemotherapy via extra-ventricular Ommaya catheter and develop milder memory loss.
authors.affiliation: Division of Neuroradiology, Toronto Western Hospital and the University of Toronto, 399 Bathurst Street 3 MCL-426, Toronto, Ontario M5T2S8, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada.
authors.forename: Benjamin Yin Ming
authors.initials: BY
authors.lastname: Kwan
authors.affiliation: Division of Neuroradiology, Toronto Western Hospital and the University of Toronto, 399 Bathurst Street 3 MCL-426, Toronto, Ontario M5T2S8, Canada.
authors.forename: Timo
authors.initials: T
authors.lastname: Krings
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital and the University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.affiliation: Division of Neuroradiology, Toronto Western Hospital and the University of Toronto, 399 Bathurst Street 3 MCL-426, Toronto, Ontario M5T2S8, Canada. Electronic address: danny.mandell@uhn.ca.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Mandell
mesh_terms: D000293:Adolescent; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D008279:Magnetic Resonance Imaging; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D003561:Cytarabine; D008727:Methotrexate
keywords: Ommaya reservoir; Papez circuit; Toxic leukoencephalopathy