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Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss

From the Division of Behavioral Medicine and Departments of Diagnostic Imaging, Radiation Oncology, and Hematology/Oncology, St Jude Children’s Research Hospital; Departments of Pediatrics and Radiology, University of Tennessee College of Medicine; and Departments of Electrical and Biomedical Engineering, University of Memphis, Memphis, TN.

Address reprint requests to Raymond K. Mulhern, PhD, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794; email raymond.mulhern{at}stjude.org

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma.

PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM.

RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory.

CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.

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