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Evidence for cerebellar-frontal subsystem changes in children treated with intrathecal chemotherapy for leukemia:
P G Lesnik1, K T Ciesielski, B L Hart
1Department of Psychology, The University of New Mexico, Albuquerque 87131, USA. lesnik@unm.edu
Insights
Childhood acute lymphoblastic leukemia (ALL) treatment with intrathecal methotrexate impacts the developing cerebellar-frontal system. This study reveals structural and functional deficits in survivors, highlighting long-term effects on brain development.
Area of Science:
- Neuroscience
- Pediatric Oncology
- Radiology
Background:
- Early childhood brain insults can affect neocerebellar and frontal lobe development.
- Intrathecal methotrexate is a common treatment for childhood acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To investigate the structural and functional impact of intrathecal methotrexate treatment in childhood ALL on the cerebellar-frontal subsystem.
- To utilize advanced imaging and neuropsychological methods to assess treatment effects in survivors.
Main Methods:
- Quantitative magnetic resonance imaging (MRI) was used to compare cerebellar lobuli and prefrontal cortex morphometry.
- Neuropsychological tests assessed attention, memory, and visuomotor skills in ALL survivors and controls.
- Statistical effect size models and regression analysis were employed to interpret findings, especially in small sample sizes.
Main Results:
- ALL survivors showed significant deficits in cerebellar lobuli VI-VII and prefrontal cortex morphometry.
- Neuropsychological performance was impaired in ALL survivors, consistent with cerebellar-frontal subsystem involvement.
- Effect size modeling confirmed these structural and functional deficits.
Conclusions:
- Intrathecal methotrexate treatment before age 5 in children with ALL has lasting structural and functional consequences.
- The developing neocerebellar-frontal subsystem is particularly vulnerable to this treatment.
- Findings underscore the importance of monitoring neurodevelopmental outcomes in childhood cancer survivors.
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.