Potentially reversible acute cerebellar toxicity associated with Minnelide

Neuroradiology. 2017 Apr;59(4):419-421. doi: 10.1007/s00234-017-1809-z. Epub 2017 Mar 16.

Abstract

Purpose: Minnelide is an experimental antineoplastic agent that is currently the subject of a phase 1 clinical trial for the treatment of pancreatic and gastrointestinal malignancies. In this study, we documented two cases of reversible acute cerebellar toxicity (REACT) associated with Minnelide and compared its radiological manifestations with other cerebellotoxic agents.

Methods: Both patients had histories of progressive metastatic cancer and participated in a phase 1 clinical trial with Minnelide. They had an MRI examination including T2WI, FLAIR and SWI, axial and coronal DWI, and ADC map on admission and follow up.

Results: In each patient, the initial MRI demonstrated increased signal on FLAIR and restricted diffusion in the cerebellar cortex without involvement of deep cerebellar nuclei or supratentorial areas. The presenting symptoms and the majority of imaging findings resolved on follow up MRI.

Conclusion: To our knowledge, Minnelide has shown an uncommon radiologic pattern of isolated cerebellar cortical involvement compared to other causes of cerebellar toxicity. Since this is a new medication, physicians' familiarity with the presenting symptoms and its temporal association with the imaging findings is important.

Keywords: Cerebellar cortex; Cerebellar toxicity; Diffusion weighted imaging; Minnelide; Reversible acute cerebellar toxicity.

Publication types

  • Case Reports

MeSH terms

  • Cerebellum / diagnostic imaging*
  • Cerebellum / drug effects*
  • Clinical Trials, Phase I as Topic
  • Colonic Neoplasms / drug therapy
  • Diterpenes
  • Epoxy Compounds
  • Fatal Outcome
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Organophosphates / toxicity*
  • Pancreatic Neoplasms / drug therapy
  • Phenanthrenes / toxicity*

Substances

  • Diterpenes
  • Epoxy Compounds
  • Organophosphates
  • Phenanthrenes
  • 14-O-phosphonooxymethyltriptolide disodium salt