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Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

King TZ, Wang L, Mao H - PLoS ONE (2015)

Bottom Line: The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors.TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups.Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology & Neuroscience Institute, Georgia State University, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood.

Methods: Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors.

Results: The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors.

Conclusions: Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

No MeSH data available.


Related in: MedlinePlus

White matter differences between survivors with no radiation treatment and healthy controls.Significant white matter differences between survivors with no radiation treatment (NRT) and healthy controls (HC) were found in the empirically-identified white matter regions from TBSS. White matter skeleton (color coded in green) is overlaid on a T1 weighted image. Clusters of significantly lower fractional anisotropy (FA) for survivor group are in orange and red. No statistically significant correlation between intellectual performance and the white matter FA was found in these areas.
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pone.0131744.g003: White matter differences between survivors with no radiation treatment and healthy controls.Significant white matter differences between survivors with no radiation treatment (NRT) and healthy controls (HC) were found in the empirically-identified white matter regions from TBSS. White matter skeleton (color coded in green) is overlaid on a T1 weighted image. Clusters of significantly lower fractional anisotropy (FA) for survivor group are in orange and red. No statistically significant correlation between intellectual performance and the white matter FA was found in these areas.

Mentions: Distinct from prior studies, we compared survivors without radiation treatment to healthy controls to investigate whether the neurological complications which are common among most brain tumor survivors (e.g., brain tumor itself and hydrocephalus) may disrupt white matter development without the factor of radiation treatment. In this case, lower FA was observed in the corpus callosum and the left frontal regions (Fig 3) in the NRT group. Although lower FA in these two regions also was observed in the RT groups, more brain regions appear to be affected in the RT group. Taking together, these observations suggest that the white matter in corpus callosum and the left frontal area may be particularly vulnerable to damage from common neurological factors (e.g. brain tumor itself, hydrocephalus). However, no statistically significant correlations with IQ were found between these empirically identified regions (Table 3) in NRT and HC groups. This lack of correlation is likely due to the similar and restricted range of intellectual performance within the high average range in both NRT and HC groups (and notably smaller standard deviations compared to the RT group). Yet, it appears that FA is sensitive to white matter differences in NRT versus HC groups.


Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

King TZ, Wang L, Mao H - PLoS ONE (2015)

White matter differences between survivors with no radiation treatment and healthy controls.Significant white matter differences between survivors with no radiation treatment (NRT) and healthy controls (HC) were found in the empirically-identified white matter regions from TBSS. White matter skeleton (color coded in green) is overlaid on a T1 weighted image. Clusters of significantly lower fractional anisotropy (FA) for survivor group are in orange and red. No statistically significant correlation between intellectual performance and the white matter FA was found in these areas.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492692&req=5

pone.0131744.g003: White matter differences between survivors with no radiation treatment and healthy controls.Significant white matter differences between survivors with no radiation treatment (NRT) and healthy controls (HC) were found in the empirically-identified white matter regions from TBSS. White matter skeleton (color coded in green) is overlaid on a T1 weighted image. Clusters of significantly lower fractional anisotropy (FA) for survivor group are in orange and red. No statistically significant correlation between intellectual performance and the white matter FA was found in these areas.
Mentions: Distinct from prior studies, we compared survivors without radiation treatment to healthy controls to investigate whether the neurological complications which are common among most brain tumor survivors (e.g., brain tumor itself and hydrocephalus) may disrupt white matter development without the factor of radiation treatment. In this case, lower FA was observed in the corpus callosum and the left frontal regions (Fig 3) in the NRT group. Although lower FA in these two regions also was observed in the RT groups, more brain regions appear to be affected in the RT group. Taking together, these observations suggest that the white matter in corpus callosum and the left frontal area may be particularly vulnerable to damage from common neurological factors (e.g. brain tumor itself, hydrocephalus). However, no statistically significant correlations with IQ were found between these empirically identified regions (Table 3) in NRT and HC groups. This lack of correlation is likely due to the similar and restricted range of intellectual performance within the high average range in both NRT and HC groups (and notably smaller standard deviations compared to the RT group). Yet, it appears that FA is sensitive to white matter differences in NRT versus HC groups.

Bottom Line: The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors.TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups.Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology & Neuroscience Institute, Georgia State University, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood.

Methods: Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors.

Results: The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors.

Conclusions: Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white matter integrity. Radiation and adjunct chemotherapy treatment may play a role in greater white matter disruption. The relationships between white matter integrity and IQ, as well as cumulative neurological risk factors exist in young adult survivors of childhood brain tumors.

No MeSH data available.


Related in: MedlinePlus