Evidence for cerebellar-frontal subsystem changes in children treated with intrathecal chemotherapy for leukemia: enhanced data analysis using an effect size model.
BACKGROUND
Following brain insult in early childhood, the later maturing neocerebellum and frontal lobes frequently show abnormalities.


OBJECTIVE
To investigate the morphologic characteristics and function of a proposed cerebellar-frontal subsystem in children treated for acute lymphoblastic leukemia (ALL) with intrathecal methotrexate using quantitative magnetic resonance imaging, neuropsychological measures, nonlinear multiple regression analysis, and a statistical effect size model that augments interpretive validity of nonsignificant statistical findings, particularly from small sample size studies.


METHODS
Comparison and relationship of magnetic resonance imaging morphometry of cerebellar lobuli I-V and VI-VII and prefrontal cortices, and performance on 5 neuropsychological tests assessing visual-spatial attention, short-term memory, and visuomotor organization and coordination between childhood survivors of ALL and a matched control group.


METHODS
Ten childhood survivors of ALL treated between 1982 and 1989 with standard 3-year intrathecal chemotherapy, and matched control subjects.


METHODS
Morphometric results of cerebellar lobuli I-V and VI-VII and prefrontal cortices, and results of Trail-Making Tests, Rey-Osterreith Complex Figure Test, WISC-III Coding.


RESULTS
Significant effect size model values for outcome measures in the ALL group support deficits in lobuli VI-VII and prefrontal cortices, and neuropsychological performance. Multiple regression analysis results were consistent with hypothesized involvement of a cerebellar-frontal brain subsystem.


CONCLUSIONS
Treatment of children with ALL with intrathecal methotrexate before 5 years of age has structural and functional effects on the developing neocerebellar-frontal subsystem.
Lesnik
P G
PG
Department of Psychology, The University of New Mexico, Albuquerque 87131, USA. lesnik@unm.edu
Ciesielski
K T
KT
Hart
B L
BL
Benzel
E C
EC
Sanders
J A
JA
D000293:Adolescent; D000886:Anthropometry; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D002531:Cerebellum / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development*; D002648:Child; D003071:Cognition / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate