White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

BACKGROUND: While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. METHODS: Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation.

Feasibility of conducting long-term follow-up of children and infants treated for CNS tumors on the same cooperative group clinical trial protocol.

Given the barriers to conducting long-term assessment of neurocognitive and psychosocial functioning of those treated in infancy for central nervous system (CNS) tumors, a multi-site feasibility study was conducted. The primary objective was to demonstrate that it is feasible to identify, locate and assess the functioning of children treated on the same protocol 10-years post-treatment. Six sites obtained institutional approval, identified and recruited subjects, and obtained comprehensive neurocognitive and psychosocial data. All feasibility objectives were met. Barriers to participation included length of time for Institutional Review Board submission and review, clinical demands, limited eligible participants at individual institutions, difficulty locating long-term subjects and stipend/reimbursement concerns. Results indicate that long-term studies are feasible and essential given the need to address long-term issues of children treated at a young age for CNS tumors, especially as they relate to later academic and vocational planning, but require significant coordination and commitment of cooperative group and institutional resources.

Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: impact on working memory.

Brain tumors are the leading cause of death and disability from childhood disease in developed countries. Pediatric posterior fossa tumors are often effectively controlled with a combination of surgery, radiation, and chemotherapy, depending on tumor type. White matter injury following resection of tumor and radiation treatment is associated with cognitive declines, including working memory deficits. We investigated how brain injury following treatment for posterior fossa tumors results in deficits in working memory. We used diffusion tensor imaging and probabilistic tractography to examine the structural integrity of cerebello-thalamo-cerebral tracts in patients and healthy children. We also compared working memory outcome in patients versus controls, and related this function to integrity of cerebello-thalamo-cerebral tracts. Bilateral cerebello-thalamo-cerebral tracts were delineated in all participants. Patients treated with a combination of surgery and radiation had lower mean anisotropy and higher mean radial diffusivity within the cerebellar regions of the cerebello-thalamo-cerebral tract compared to patients treated with surgery only and healthy controls. Poorer working memory scores were observed for the cranial radiation group relative to controls. Reduced anisotropy and higher radial diffusivity within the entire cerebello-thalamo-cerebral pathway predicted lower working memory. Our finding that working memory function is related to the integrity of cerebello-thalamo-cerebral connections is a novel contribution to the understanding of cerebral-cerebellar communication. Identifying differences in the structural integrity of white matter for specific pathways is an essential step in attempting to localize the effects of posterior fossa tumors and their treatment methods.

Cognitive outcome in pediatric brain tumor survivors: delayed attention deficit at long-term follow-up.

BACKGROUND: Treatment of childhood brain tumors has often been associated with long-term cognitive morbidity in children. Our previous research identified age at diagnosis, polytherapy and brain radiation dose as treatment factors affecting neuropsychological outcome most strongly in children with cancer 1. Our current goal was to measure the change across different cognitive functions. PROCEDURE: This study examined the cognitive outcome over repeat testing in a heterogeneous sample of 18 children with brain tumors. Tumor types included medulloblastoma and glioma. ANOVA's for repeated measures were used to evaluate the changes in cognitive domains across follow-up evaluations. RESULTS: Consistent with previous findings, the most deleterious effects were seen on IQ indices of non verbal cognitive ability, visual perceptual skills and information processing speed. Analyses reveal that the attentional factor, Freedom from Distractibility, is the only IQ index that declines over subsequent testing. The statistical decline was attributable to a significant decline on the arithmetic subtest, as well as a non-significant trend for the auditory attention span subtest. CONCLUSIONS: This study reveals that while most indices remained stable over repeat testing, auditory attention and concentration skills decline. Long-term outcome is discussed in light of the high prevalence of attention and mathematic difficulties reported in these children and the need for preventive and remedial approaches.

Evening and morning EEG differences between young men and women adults.

Evening and morning waking EEG (eyes closed) was recorded in 16 women and 13 men aged 18-26 years old. Participants were fitted with a 13-electrode montage (Fp1, Fp2, FZ, F7, F8, C3, C4, T3, T4, P3, P4, O1, and O2) referred to linked ears. For each recording electrode, EEG total spectral amplitude power (microV/Hz, 0.75-19.75 Hz) was compared using 2 (Gender) x 2 (Moments) analyses of variance for repeated measures and LSD post-hoc tests. We found significant simple Gender effects, with women displaying higher EEG values for Central, Frontal, Parietal, and left Temporal leads. Simple Moment effects were also found, with lower morning values in Temporal and left Frontal recording sites. A Gender x Moment interaction was found at the right Frontal recording site. No significant effects were found for Prefrontal and Occipital recording sites, whatsoever. These results bring new understandings of gender and time of day effects in waking EEG and point to different sensitivity in different cortical areas. The present results could explain some of the observations related to gender differences in cognitive performance.

Correlation between evening and morning waking EEG and spatial orientation.

The prefrontal, frontal, and parietal EEG of 16 healthy young adults (seven men, nine women; age=22.57+/-4.2) was recorded during the waking state (eyes closed) in the evening before and the morning following a second consecutive night spent in a sleep laboratory. Following the morning EEG recording session, participants were tested in a human-size maze upon five learning trials of a four-intersection route. Results on the fifth trial served as the learning index. We found a significant positive correlation between time taken to carry out the route and prefrontal, frontal EEG alpha-2 (10.0-12.75 Hz), and sigma (11.5-14.5 Hz) frequency bands. We also found that prefrontal and frontal theta activity correlated negatively with number of errors. No correlation was found between performance and neither alpha-1 (8.0-9.75 Hz) nor parietal EEG activity. These results confirm the involvement of the prefrontal and frontal cortices in the mechanisms responsible for modulating spatial orientation.