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Open Access Research article

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

Marita Daams1, Ilse Schuitema23*, Bob W van Dijk4, Eline van Dulmen-den Broeder3, Anjo JP Veerman3, Cor van den Bos5 and Leo MJ de Sonneville2

Author Affiliations

1 Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands

2 Department of Clinical Child and Adolescent Studies, Faculty of Social Sciences & Leiden Institute for Brain and Cognition, Leiden University, Wassenaarseweg 52, P.O. Box 9555, 2300 RB, Leiden, The Netherlands

3 Department of Pediatrics, Division of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, The Netherlands

4 Department of Physics and Medical Technology and the department of Clinical Neurophysiology, VU University Medical Center, Amsterdam, The Netherlands

5 Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam Medical Center, Amsterdam, The Netherlands

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BMC Neurology 2012, 12:84  doi:10.1186/1471-2377-12-84

Published: 28 August 2012

Abstract

Background

Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.

Methods

Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.

Results

In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).

Conclusions

The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.

Keywords:
Late effects; Childhood cancer; Magnetoencephalography; Resting state; Oscillatory power; Neuropsychology; Accelerated aging