Abstract Details

Title Biopsy-Proven Multifocal Necrotizing Leukoencephalopathy Following Systemic Methotrexate Monotherapy for CNS Metastasis of Non-Hodgkin Lymphoma

Topic Neuro-oncology

Presentation(s) P01 - (-)

Poster/Presentation
Number 107

Objective

Background There is a variety of neurotoxicities associated with systemic or intrathecal administration of MTX. MNL typically occurs after combined MTX and cranial RT (Rubinstein et al 1975) and is typically irreversible and fatal.

Design/Methods Case Report.

Results At age 36, the patient was treated with CHOP-R for systemic Non-Hodgkin lymphoma. Two months after treatment he was diagnosed with ocular and leptomeningeal lymphoma and received high-dose (8gm/M2) intravenous MTX. He developed progressive vision loss and left limb weakness during treatment and immediately after the 5th dose became somnolent and awoke with severe left limb paresis. He was referred for further evaluation. Exam revelaed bilateral optic atrophy, mild left facial weakness, severe left limb weakness, confusion and agitation. Review of serial brain MRIs showed development of multifocal T2/FLAIR hyperintensities in cerebral hemisphere white matter, basal ganglia and cerebellum, mild contrast enhancement, without restricted diffusion. Homozygosity for MTHFR C677T was identified in blood. Cerebellar lesion biopsy revealed vacuolization and sparse axonal swelling, consistent with myelinolysis, and lipid-laden macrophages. CSF metabolites consistent with MTX toxicity were elevated, but must be interpreted with caution because CSF was contaminated by RBC. He was treated with high dose folic acid and memantine. Six months later, blindness persists but his mentation and limb weakness are significantly improved.

Conclusions MNL occurs almost exclusively following combined intrathecal or systemic MTX and brain RT. This case adds to the repertoire of neurotoxicity of systemic MTX monotherapy. The pathology findings are identical to MNL after combination treatment except for less evidence of axonal damage. It is speculative if his clinical improvement is attributable to therapy with folic acid and memantine or to a milder degree of tissue injury than is typical of MNL.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Mark Cohen	Mark Cohen has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Lisa R. Rogers, DO, FAAN (Henry Ford Hospital)	Dr. Rogers has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novocure .

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