Transient tetraparesis after intrathecal and high-dose systemic methotrexate

Abstract

 Aggressive polychemotherapy, intrathecal cytostatic prophylaxis and cranial irradiation have contributed to the remarkable improvement in the prognosis of acute lymphoblastic leukemia (ALL) and subtypes of high-grade non-Hodgkin's lymphoma (NHL) and the reduction of central nervous system (CNS) relapses. Early and late neurologic changes have been observed after different CNS-directed therapies. We report on the rare event of an acute tetraparesis after methotrexate (MTX) without other CNS-directed therapy. A young female with a diffuse large B-cell lymphoma developed signs of meningeal irritation a few hours after intrathecal prophylaxis with MTX, cytosine-arabinoside and dexamethasone. She recovered quickly. Ten days after her last course of systemic chemotherapy including high dose MTX she was admitted with a tetraparesis and motoric aphasia. A computer assisted tomography (CT) scan was normal. On magnetic resonance imaging (MRI) hyperintense white matter lesions were visible in the periventricular white matter. Initially, the radiologic signs were progressive while the patient's clinical condition improved. MRI controls after complete neurologic normalization revealed delayed partial regression of the white matter abnormalities. The patient has now been free of neurologic symptoms for 16 months. This case report demonstrates acute and subacute neurotoxic effects of MTX in the same patient and illustrates that radiologic CNS changes can persist irrespective of the disappearance of clinical symptoms.