Abstract Details

Title Cough-headache as a Novel Presentation of Methotrexate Neurotoxicity

Topic Neuro-oncology

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-004

Objective To describe a novel presentation of methotrexate neurotoxicity and leukoencephalopathy.

Background Methotrexate (MTX) administered intrathecally and in high dose has been shown to be effective in treatment of leukemia by clearing CNS involvement but carries risk of reversible acute-onset and delayed-onset neurotoxicity. Delayed-onset neurotoxicity has a characteristic imaging appearance named methotrexate-induced leukoencephalopathy (MTX-LE). Previously reported cases of MTX-LE have presented with paresis, aphasia, anarthria, opisthotonos, and confusion. We describe a case with novel presenting symptoms of cough-induced headache (cough-headache) and diplopia.

Design/Methods Case report and review of literature.

Results A 60-year-old man with chronic lymphocytic leukemia (CLL) with significant subarachnoid extension recently treated with two cycles of high dose methotrexate 3000 mg/m2 IV (other prior treatment included venetoclax and rituximab, acalabrutinib, pirtobrutinib, zanubrutinib, leucovorin) and undergoing intrathecal “triple chemotherapy” including methotrexate 12 mg, hydrocortisone 15 mg, and cytarabine 50 mg presented two hours after seventh IT chemotherapeutic infusion with cough-headache. Neurological examination notable for horizontal diplopia present on far-gaze. CSF analysis revealed mild protein elevation to 64 but negative viral panel. MRI brain revealed bilateral subcortical non-enhancing, non-restricted T2 hyperintensities consistent with MTX-LE. Further MTX therapy was held and dextromethorphan was administered with resolution of symptoms within 3 days.

Conclusions Sudden severe cough headache with diplopia is a novel and unique presentation of acute MTX toxicity in the setting of MTX-LE which has not been previously described. Patients receiving high-dose or intrathecal MTX are also at high risk of spontaneous intracerebral hemorrhage which should first be ruled out. Following initial imaging, MTX neurotoxicity should be considered in the differential with appropriate imaging ordered to evaluate for its presence.

Authors/Disclosures
Philion Gatchoff, MD (OU Health) PRESENTER	Dr. Gatchoff has nothing to disclose.
Estevao P. Ribeiro, MD	Dr. Ribeiro has nothing to disclose.
Evan Fields, MD (Ou health)	Dr. Fields has nothing to disclose.
Ahmad Al-Awwad, MD (Houston Methodist)	Dr. Al-Awwad has nothing to disclose.

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