Spinal Cord Toxicity from Intrathecal Chemotherapy: A Case with Clinicopathologic Correlation

World Neurosurg. 2019 Aug:128:381-384. doi: 10.1016/j.wneu.2019.05.123. Epub 2019 May 23.

Abstract

Background: Myelopathy of the dorsal columns is a rare complication of intrathecal (IT) chemotherapy that occurs most frequently with IT methotrexate and cytarabine. This diagnosis is made with a combination of magnetic resonance imaging, somatosensory evoked potentials, and elevated cerebrospinal fluid (CSF) protein levels, particularly myelin basic protein.

Case description: A 73-year-old man with blastic plasmacytoid dendritic cell neoplasm and known central nervous system involvement underwent standard treatment, including 5 doses of IT cytosine arabinoside. Following this, he had documented CSF clearance of disease. One year later, he developed progressive lower extremity weakness, numbness, and bowel/bladder dysfunction. Magnetic resonance imaging and repeat CSF analysis demonstrated recurrence, and he underwent further IT administration of methotrexate and cytarabine. CSF clearance of malignant cells was again established. However, weakness progressed to quadriplegia; loss of bowel/bladder control; and severe sensory loss, particularly vibration and proprioception. Repeat magnetic resonance imaging demonstrated high signal intensity in bilateral posterior columns. A lower thoracic spine dorsal column biopsy revealed cord destruction and diffuse macrophage infiltration with profound destruction of the neuropil.

Conclusions: Although dorsal column myelopathy has previously been described in association with IT chemotherapy, this has solely been diagnosed on the basis of clinical examination, electrodiagnostic criteria, radiographic findings, and CSF analysis. This case provides a pathologic evaluation of an antemortem obtained specimen revealing diffuse macrophage infiltration and profound destruction of the neuropil. Whereas the mechanism underlying spinal cord toxicity following IT chemotherapy remains largely unknown, this case demonstrates a potentially macrophage-mediated process.

Keywords: Dorsal column myelopathy; Intrathecal chemotherapy; Neuro-oncology.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cytarabine / administration & dosage
  • Dendritic Cells / pathology
  • Electrodiagnosis
  • Evoked Potentials, Somatosensory
  • Humans
  • Injections, Spinal
  • Magnetic Resonance Imaging
  • Male
  • Methotrexate / administration & dosage
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Spinal Cord Diseases / chemically induced*
  • Spinal Cord Diseases / diagnosis*
  • Spinal Cord Diseases / therapy
  • Spinal Cord Neoplasms / drug therapy
  • Spinal Cord Neoplasms / pathology*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Methotrexate