The Neurotoxicity On The Central Nervous System From Intrathecal Injections And High-dose Methotrexate Therapy In Children With Acute Lymphoblastic Leukemia

Purpose: The importance of prophylactic central nervous system (CNS) treatment to prevent CNS relapse of acute lymphoblastic leukemia (ALL) in childhood is generally accepted. CNS irradiation is gradually being replaced by systemic high-dose methotrexate as prophylactic, CNS-directed treatment. We hare an obligation to study prospectively the side effects of the new treatment. Enolase is a dimeric cytoplasmic enzyme whose double gamma isoenzyme, neuron-specific enolase (NSE), is predominantly found in neuronal and neuroendocrine tissues. Cell injury causes its release into the blood and cerebrospinal fluid (CSF). NSE has been established as a reliable marker of neuronal damage in various neurologic disorders. EEC recordings have become a popular approach for judgement on the functional integrity of CNS. We investigate possible side effects on the central nervous system from intrathecal injections and high-dose methotrexate therapy (HDMTX+IT) given during treatment for ALL in childhood.Patients and Methods: Forty-two children aged from 5 to 11 years with ALL participated in the study. Children who had the history of ALL less than one year were twenty .While twenty-two children had ALL more than one year . None of the children had any neurologic symptoms during the treatment. Cerebrospinal fluid was sampled for analyses of neuron-specific enolase at the beginning of treatment and after ten days of treatment. There were twenty-five children check CSF again after twenty-eight days of treatment. Electroencephalographic examinations were performed in 38 children at the beginning of treatment and after ten days of treatment.Results :NSE concentration was no different between children who had ALL more than one year and less than one year. The NSE content increased from (3.9 0.5) ng/ml before the start of treatment to (6. 5 0. 6) ng/ml at day 10 and then decreased to (4. 1 0. 6) ng/ml at day 28. 21 of 38 available EEGsshowed slight to moderate slowing already at the beginning of treatment . The most frequent EEG abnormalities observed were disturbances of the background activity. The EEGs remained abnormal but did not worsen further on day 10. There were no statistically significant changes .Conclusions : NSE is a useful marker for acute brain damage in acute lymphoblastic leukemia children. The evaluation of conventional EEC recordings is not a very helpful measure for predicting the degree of neurological disturbances in children with ALL.