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International Journal of Hematology

, Volume 108, Issue 6, pp 630–636 | Cite as

Characteristics of methotrexate-induced stroke-like neurotoxicity

  • Kentaro Watanabe
  • Yuki Arakawa
  • Eiji Oguma
  • Taichi Uehara
  • Masato Yanagi
  • Chigusa Oyama
  • Yuhachi Ikeda
  • Koji Sasaki
  • Kiyotaka Isobe
  • Makiko Mori
  • Ryoji Hanada
  • Katsuyoshi Koh
Original Article

Abstract

Intrathecal administration of methotrexate (IT-MTX) can lead to neurotoxicity. MTX-induced neurotoxicity occasionally manifests with a stroke-like presentation that is difficult to distinguish from genuine stroke. We retrospectively reviewed records of nine patients with leukemia or lymphoma and episodes of stroke-like presentation at our institute between 2010 and 2015 for whom magnetic resonance imaging (MRI) data were available. Coagulation test results were compared between the two diagnostic groups. Four patients were diagnosed with MTX-induced stroke-like neurotoxicity. The first neurological event occurred 10–13 days after the fourth or later IT-MTX treatment. All four patients had hemiparalysis, two exhibited disturbed consciousness and three presented with speech disorders. Fibrin/fibrinogen degradation products (FDP) and D-dimer values were within normal ranges. MRI revealed bilateral lesions with restricted diffusion in all four cases. Neurological symptoms fluctuated and resolved within 5 days, and IT-MTX was subsequently re-initiated in all four cases. One patient developed transient hemiparalysis after a subsequent IT-MTX treatment, but this did not recur thereafter. Bilateral lesions on MRI and normal coagulation are indicative of MTX-induced stroke-like neurotoxicity. Continuation of IT-MTX after these events is generally feasible, but adverse event risk should be carefully weighed against anti-tumor benefits.

Keywords

Methotrexate Neurotoxicity Leukoencephalopathy 

Notes

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest to disclose.

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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Kentaro Watanabe
    • 1
    • 3
  • Yuki Arakawa
    • 1
  • Eiji Oguma
    • 2
  • Taichi Uehara
    • 1
  • Masato Yanagi
    • 1
  • Chigusa Oyama
    • 1
  • Yuhachi Ikeda
    • 1
  • Koji Sasaki
    • 1
  • Kiyotaka Isobe
    • 1
  • Makiko Mori
    • 1
  • Ryoji Hanada
    • 1
  • Katsuyoshi Koh
    • 1
  1. 1.Department of Hematology/OncologySaitama Children’s Medical CenterSaitamaJapan
  2. 2.Department of RadiologySaitama Children’s Medical CenterSaitamaJapan
  3. 3.The Department of PediatricsThe University of TokyoTokyoJapan

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