Intrathecal Chemotherapy-Related Myeloencephalopathy in a Young Child with Acute Lymphoblastic Leukemia

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.

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

“…Spinal involvement (seven patients, [16][17][18][19][20][21][22]: Two patients had flaccid quadriplegia with sensory and sphincter disorders. The other five patients had solely motor involvement; paraplegia was accompanied in three cases by pyramidal signs (Babinski sign, brisk osteo-tendinous reflexes).…”

“…14,15 The exact incidence of these complications is difficult to determine, as most data come from isolated case reports. [15][16][17][18][19][20] Similarly, the outcome of children with acute neurotoxicity is poorly documented. Yet improvements in outcome in recent years have placed the accent on prevention of treatment sequels.…”

Acute Polyneuropathy in Children with Acute Lymphocytic Leukemia: Case Report and Systemic Review of the Literature

“…Acute CNS complications, seizures and acute encephalopathy are extremely rare, but have been reported. 19 Methotrexate, cytarabine, and corticosteroids (triple-drug therapy) are the most common drugs used intrathe--cally. They produce both central and peripheral nervous systems toxicity.…”

Neurological improvement and rehabilitation potential following toxic myelopathy due to intrathecal injection of doxorubicin

“…The course is, in the majority of cases, bad, often leading to death or severe neurological sequelae. [1][2][3][4][5][6][7][8][9][10][11][12] In the last 40 years, 39 cases were reported in the literature. Only 25% of patients recover completely.…”

“…Only 25% of patients recover completely. 12 The principal cause is erroneous intrathecal administration of vincristine, methotrexate and cytosine-arabinoside (ARA-C).…”