title: Reduced neuroanatomic volumes in long-term survivors of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls.
  
  
  METHODS
  We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls.
  
  
  RESULTS
  Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume.
  
  
  CONCLUSIONS
  Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.
authors.affiliation: Department of Pediatric Medicine, Oslo University Hospital, Mailbox 4950 Nydalen, N-0424 Oslo, Norway. bernward.zeller@ous-hf.no
authors.forename: Bernward
authors.initials: B
authors.lastname: Zeller
authors.forename: Christian K
authors.initials: CK
authors.lastname: Tamnes
authors.forename: Adriani
authors.initials: A
authors.lastname: Kanellopoulos
authors.forename: Inge K
authors.initials: IK
authors.lastname: Amlien
authors.forename: Stein
authors.initials: S
authors.lastname: Andersson
authors.forename: Paulina
authors.initials: P
authors.lastname: Due-Tønnessen
authors.forename: Anders M
authors.initials: AM
authors.lastname: Fjell
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Walhovd
authors.forename: Lars T
authors.initials: LT
authors.lastname: Westlye
authors.forename: Ellen
authors.initials: E
authors.lastname: Ruud
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009445:Neuroanatomy; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D015996:Survival Rate; D017741:Survivors; D055815:Young Adult