Regional white matter volume and the relation with attentional functioning in survivors of malignant pediatric brain tumors

Author(s):  
John O. Glass ◽  
Raymond K. Mulhern ◽  
Holly A. White ◽  
Gina M. Wilkinson ◽  
Wilburn E. Reddick
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20023-20023
Author(s):  
M. M. Abdel Wahab ◽  
H. Hussien ◽  
K. M. Maher

20023 Purpose: To evaluate the delayed adverse changes in neuro-cognitive functions as well as white matter damage in radiated survivors of pediatric brain tumors. Methods: Forty two children (22 males) with primary brain tumors who were only treated with cranial radiation, were recruited. 28 patients were treated for low risk medulloblastoma, 10 patients for low grade astrocytoma, 3 patients for low grade ependymoma, and 1 patient for craniopharyngioma. Their ages ranged from 3 to 18 years (mean 10.3±3.98 years).They were subjected, initially just before radiotherapy and at follow-up 1–2 year after completion of cranial radiation, to serial clinical and neuropsychological assessments including Wechseler Intelligence Scale for Children, Vineland social maturity test, Benton Visual Memory Test, and Revised Behavior Problem Checklist. Magnetic resonance scans were also performed to detect the presence of white matter damage before radiotherapy and at follow up. Results: Initially, after surgery and before radiation, intelligence test scores were below normal scores for age and this was of high statistical significance (Total IQ: t= -3.02, P= 0.006). Visual memory test showed evidence of organicity in all cases. Social maturity showed a statistically significant decline as well (t= -2.11, P= 0.04). Follow-up after radiotherapy showed further decline with high statistical significance (Total IQ t= 3.228, P=0.003; visual memory t= 4.08, P= 0.001); An attentional problem has emerged (t= -6.12, P= 0.00). Both radiation dose and volume of radiation showed negative and statistically significant correlation with IQ. Age at diagnosis correlated positively and significantly with IQ ( r= 0.601, P=0.001). Multiple linear regression showed impaired neurocognitive function which was correlated with the degree of white matter damage. (standardized B= -0.577, P= 0.001) and young age at diagnosis (standardized B= -0.427, P= 0.014). Conclusions: Cranial radiation in pediatric brain tumors is associated with a decline in multiple neurocognitive functions including total IQ, visual memory, and attention; which are related to the toxic effect of cranial radiation on white matter of the brain especially in young age of childhood with high dose and whole cranial radiation. No significant financial relationships to disclose.


Cancer ◽  
2003 ◽  
Vol 97 (10) ◽  
pp. 2512-2519 ◽  
Author(s):  
Wilburn E. Reddick ◽  
Holly A. White ◽  
John O. Glass ◽  
Gregory C. Wheeler ◽  
Stephen J. Thompson ◽  
...  

2021 ◽  
Vol 22 (9) ◽  
pp. 4953
Author(s):  
Natalie M. Zahr ◽  
Kilian M. Pohl ◽  
Allison J. Kwong ◽  
Edith V. Sullivan ◽  
Adolf Pfefferbaum

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Lawrence A. Donehower ◽  
Michael E. Scheurer ◽  
Chad J. Creighton

AbstractThe global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.


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