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. Design: 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. Participants: Ten childhood survivors of ALL treated between 1982 and 1989 with standard 3-year intrathecal chemotherapy, and matched control subjects. Main Outcome Measures: 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. Conclusion: Treatment of children with ALL with intrathecal methotrexate before 5 years of age has structural and functional effects on the developing neocerebellar-frontal subsystem.