Leukoencephalopathy and Cortical Laminar Necrosis Associated with Intrathecal Methotrexate and Cranial Irradiation

Abstract

Necrosis Associated with Intrathecal Methotrexate and Cranial Irradiation. 2003; 23(3-4): 167-170 With the advent of chemotherapy, mortality rates in children with acute lymphoblastic leukemia (ALL) have decreased. Though prophylactic treatment of the central nervous system (CNS) to prevent leukemic infiltration has dramatically reduced the incidence of CNS relapse and improved the survival in pediatric acute lymphoblastic leukemia, it is associated with serious sequelae. Various reports of neurotoxicity have been described, ranging from decreased intelligence quotient scores, impaired memory and attention span to severe leukoencephalopathy. 1 We describe a unique case of neurotoxicity associated with prophylactic cranial irradiation and intrathecal MTX. Case reportA four-year old boy was diagnosed as having central nervous system negative acute lymphoblastic leukemia (ALL) in August 1997. He was treated with a high-risk acute lymphoblastic leukemia protocol Children's Cancer Group (CCG-1882), secondary to unfavorable cytogenetics. He achieved complete remission with induction treatment consisting of weekly intravenous vincristine, daunomycin, daily oral prednisone, and nine doses of intramuscular L-asparginase. Consolidation consisted of cranial irradiation, 1800 cGy in 12 fractions of 150 cGy each, four doses of intrathecal MTX, intravenous Cytoxan and cytarabine. Prior to start of maintenance, he received reinduction/ reconsolidation treatment along with two doses of intrathecal methtrexate. Maintenance consisted of monthly pulses of intravenous vincristine, oral prednisone, weekly oral MTX and daily oral 6-merceptopurine, with intrathecal MTX every 3 months.He was admitted as an emergency, 14 days after the last intrathecal MTX in May 1999, with left focal seizures approximately 20 months after diagnosis. He had received atotal dose of 156 mg MTX intrathecally. A computerized tomography (CT) scan of the brain on the 27 th of May revealed bilateral symmetrical periventricular hypodence white matter changes in the frontoparietal region. There were no calcifications orintracranial bleeding (Figure 1). Magnetic resonance imaging (MRI) on the 30 th of May revealed multiple high intensity areas in the subcortical and periventricular white matter on fluid attenuated inversion recovery (FLAIR) imaging representing leukoencephalopathy (Figure 2). Seizures were aborted with lorazepam, and patient was discharged on carbamezapine. Two weeks later, he was readmitted because he had changed from a talkative boy of superior intelligence into a child that only answered questions with strong stimulation. He was also having seizures. A repeat MRI on the 27 th of June, four weeks after the first MRI, revealed stable diffuse white matter changes described previously, but with emergence of bilateral cortical changes in the parietooccipital lobes, with more on the right, probably representing cortical edema ( Figure 3A). These cortical changes were more readily apparent on FLAIR sequence ( Figure 3B). Lumbar puncture ruled out ...