POTD: Treat methotrexate neurotoxicity with cough syrup!

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How do I treat methotrexate neurotoxicity?

(Yes it's a thing) 

Case from today 

12yo M w/ ALL on methotrexate therapy presents with 1 day of worsening R facial droop and R sided weakness. MRI showed non-enhancing, hyperintense signal on T2 and flair consistent with MTX leukoencephalopathy.

Methotrexate

  • Folic acid antagonist

  • Used as chemotherapeutic agent or DMARD

  • May be given orally, IV, or intrathecally

Neurotoxicity

  • Can occur anytime after methotrexate use (hours to days to weeks)

  • Symptoms include seizure or stroke-like signs: hemiparesis, hemisensory deficits, aphasia, dysarthria, diplopia, dysphagia

Proposed Mechanism

  1. Methotrexate interferes with metabolism of homocysteine

  2. Homocysteine levels rise in blood and CSF

  3. Downstream effect is NMDA receptor agonism as well as neurotoxicity

homocysteine.jpg

Treatment: Dextromethorphan

  • Theoretically, NMDA inhibitor could counteract these effects...

  • Dextromethorphan is a noncompetitive NMDA receptor antagonist.

  • Case series show improvement and even resolution of symptoms after administration of dextromethorphan.

  • Symptoms may resolve in minutes, but on average took half a day. Some patients still had neuro symptoms months later.


References

  • Afshar, M., Birnbaum, D., & Golden, C. (2014). Review of Dextromethorphan Administration in 18 Patients With Subacute Methotrexate Central Nervous System Toxicity. Pediatric Neurology, 50(6), 625–629. doi:10.1016/j.pediatrneurol.2014.01.048

  • Drachtman, R. A., Cole, P. D., Golden, C. B., James, S. J., Melnyk, S., Aisner, J., & Kamen, B. A. (2002). DEXTROMETHORPHAN IS EFFECTIVE IN THE TREATMENT OF SUBACUTE METHOTREXATE NEUROTOXICITY. Pediatric Hematology and Oncology, 19(5), 319–327. doi:10.1080/08880010290057336

  • Radiopedia: Methotrexate-related leukoencephalopathy <https://radiopaedia.org/articles/methotrexate-related-leukoencephalopathy?lang=us>

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