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Abstract
Since the mid-1960s intrathecal chemotherapy (methotrexate [MTX], cytarabine [Ara-C], or both, plus hydrocortisone) has constituted the standard approach to prophylaxis and treatment of central nervous system (CNS) leukemia and lymphoma. Intrathecal chemotherapy-related neurotoxicity has been described in a variable proportion of patients. At least 35 cases of subacute myeloencephalopathy with transient or permanent paraplegia/quadriplegia after intrathecal chemotherapy have been reported. Different factors have been cited: high cumulative MTX dose, meningeal leukemia, cranial irradiation, and preservatives in MTX and Ara-C. A direct toxic effect of the intrathecal chemotherapy seems the most likely mechanism. Early imaging studies are usually normal. We describe a nonfatal case of permanent flaccid quadriplegia after the fourth triple intrathecal chemotherapy in a 6-year-old girl with acute lymphoblastic leukemia and no evidence of meningeal involvement. Six months after intrathecal chemotherapy, CNS magnetic resonance imaging showed severe atrophy of spine, cerebellum, and cerebral hemispheres. The outcome of reported cases is diverse. No treatment has been shown to reverse neurotoxicity. Among the cases reported in the literature, complete recovery of neurologic deficits was observed in 9 patients, partial recovery with variable sequelae in 6, no recovery in 8, and 13 patients died from the initial oncologic disease or neurotoxicity progression.