title: Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia.
abstract: BACKGROUND
  Limited information is available regarding neurocognitive outcomes of children who experience seizures during treatment for acute lymphoblastic leukemia (ALL). Accordingly, the main objectives of this study were to determine the incidence and risk factors for treatment-related seizures among children with ALL, and the neurocognitive outcomes associated with treatment-related seizures.
  
  
  METHODS
  Prospective neuropsychological assessment and magnetic resonance imaging (MRI) were planned for all 498 patients with newly diagnosed ALL enrolled on the St. Jude Total Therapy XV (TOTXV) protocol at three time points. The study database was reviewed retrospectively to identify those with treatment-related seizure. To assess neurocognitive changes associated with seizure, each patient with treatment-related seizure was matched with two cohort patients without seizure for age at treatment, gender, race, and treatment intensity.
  
  
  RESULTS
  Nineteen patients developed seizure, with a 2-year cumulative risk of 3.82 ± 0.86% (SE). No risk factors were identified to be associated with the development of seizure, with a possible exception of intensive chemotherapy used on the standard/high-risk arm as compared to the low-risk arm. Neuropsychological performance of the seizure group, as compared to normative scores and nonseizure control cohort, indicated problems in attention, working memory, and processing speed. Cognitive deficits persisted 2 years after therapy, with additional declines in intellectual function observed. MRI indicated early neurotoxicity among the seizure group, as evidenced by greater leukoencephalopathy on initial examinations.
  
  
  CONCLUSIONS
  Treatment-related seizures were associated with leukoencephalopathy and decreased neuropsychological performance. Prospective studies are needed to detect changes in neurocognitive status associated with long-term functional impairment.
authors.affiliation: Mental Health and Behavioral Science Services, James A. Haley Veterans' Hospital, Tampa, Florida.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Nassar
authors.affiliation: Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Conklin
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ashford
authors.affiliation: Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Wilburn E
authors.initials: WE
authors.lastname: Reddick
authors.affiliation: Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: John O
authors.initials: JO
authors.lastname: Glass
authors.affiliation: Department of Diagnostic Radiology, Children's Hospital Central California, Madera, California.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Laningham
authors.affiliation: Departments of Oncology and Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Departments of Oncology and Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D056784:Leukoencephalopathies / Q000453:epidemiology / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012307:Risk Factors; D012640:Seizures / Q000139:chemically induced* / Q000150:complications*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D015122:Mercaptopurine; D006854:Hydrocortisone; D008727:Methotrexate
keywords: cognitive late effects; leukemia; leukoencephalopathy; seizure; working memory