Dados do Trabalho

Título

Methotrexate neurotoxicity with atypical radiologic findings

RESUMO

Case report: A 18 year old man with infiltration of the central nervous system (CNS) by T-cell acute lymphoid leukemia was treated with intrathecal chemotherapy (ITC) with dexamethasone, cytarabine and methotrexate (MTX). Two weeks later, severe lumbar arachnoiditis was diagnosed, so ITC was interrupted and an Ommaya reservoir was implanted. After 10 days, he developed aphasia and apathy. Brain magnetic resonance imaging (MRI) revealed white matter hyperintensities in T2/FLAIR (fluid attenuated inversion recovery)-weighted images in both frontal lobes, in corpus callosum and around the Ommaya reservoir, with peripheral and irregular gadolinium enhancement and areas of diffusion-water restriction. Leukemia infiltration and reservoir-associated infection were considered as possible diagnoses. CSF analysis had no neoplastic cells and cultures were negative. Despite the achievement of hematologic recovery at the end of that chemotherapy phase, he persisted with neurologic deficits. A few days later he was treated for clinical status epilepticus and a new brain MRI showed progression of the lesions. Spectroscopy had a pattern suggestive of neoplastic infiltration, but considering the normal CSF analysis and the systemic remission of leukemia it was improbable. So, a brain biopsy was performed. Fragments of deep frontal lesions showed edema, necrosis and hystiocitary inflammatory reactional areas, without lymphoid atypical infiltrates. Histokymic fungi methods tests and JC virus search were negative. The morphology observed was compatible with MTX neurotoxicity. Given the temporal relationship of the lesions with the drug administration, although there were some atypical MRI findings for this condition, MTX was withheld for 2 months. Gradually, he had neurological improvement with complete resolution of aphasia. Follow up MRI showed a decrease of lesions. Discussion: MTX leukoencephalopathy is rare and occurs in about 2 to 3,8% with MTX high dose treatments. It is commonly transient and improves with cessation of the drug. A subsequent MTX dose after the resolution of the acute phase is habitually well tolerated. Conclusion: MTX neurotoxicity typically presents as peripheral neuropathy, but it is a main differential diagnosis in CNS lesions in leukemia patients receiving ITC, particularly if neuroinfection and secondary neoplastic invasion were excluded.

Palavras Chave

Leukemia, Leukoencephalopathies, Magnetic Resonance Imaging, Methotrexate, neurotoxicity