Dataset Information

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

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.

SUBMITTER: King TZ

PROVIDER: S-EPMC4492692 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

King Tricia Z TZ Wang Liya L Mao Hui H

PloS one 20150706 7

<h4>Background</h4>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.<h4>Methods</h4>Fifty-four participants underwent diffusion tensor imaging in addition to structural M ...[more]

PMID: 26147736

Similar Datasets

Project description:Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL.In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (? 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations.Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E'; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E']; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DL(co)(corr); P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E', although impaired sustained attention and naming speed were associated with DL(co)(corr). Neurocognitive performance was associated with academic and vocational functioning.These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.

Project description:PurposeProspective and longitudinal neuroimaging studies of posterior fossa tumors are scarce. Here we evaluate the early changes in white matter and intellectual outcome up to 3 years after diagnosis.Patients and methodsTwenty-two children with posterior fossa tumors and 24 similarly-aged healthy children participated. Patients included: (a) 12 individuals who received surgery, cranial-spinal radiation (CSR), and focal radiation to the tumor bed (CSR group) and (b) 10 individuals who received local therapy, either surgery only or surgery and focal radiation to the tumor bed (Local group). Diffusion tensor imaging (DTI) and intelligence measures were obtained an average of 3 months after diagnosis and then at 12, 24, and 36 months later. DTI tractography and voxel-wise approaches were employed. The Neurological Predictor Scale was used to summarize the type and amount of treatment for PF tumor patients. Linear mixed modelling was used to evaluate group differences at baseline and changes over time in DTI metrics for both the specific white matter tracts and voxel-wise, as well as for intelligence measures.ResultsBased on tractography, patients treated with CSR had significantly higher Axial and Mean diffusivity in the cortical-spinal tracts (CST) 3 month after diagnosis - particularly on the right side, p < .003, compared to healthy children. Mean diffusivity in right CST decreased over time in this group of patients, p = .001. No differences compared to controls were evident in specific tracts for the Local group, p > .10. Voxel-wise analyses revealed multiple areas of white matter compromise in both patients groups. Notably, both patient groups had lower scores on intelligence measures compared to the Control group: The CSR group displayed lower performance 3 months following diagnosis, ps < 0.001, and their performance remained stable over time ps > 0.10, whereas the Local group displayed no differences at 3 months, ps> 0.10, but their performance declined over time, ps < 0.01. At baseline, higher MD in right CST predicted lower Perceptual Reasoning scores across all participants, p = .001. Furthermore, lower FA in left IFOF at baseline predicted decline in Processing Speed over time, p = .001. In patients, more aggressive treatment protocols and presence of mutism were related to lower performance on intelligence measures at baseline, ps < 0.04.ConclusionsChildren treated with CSR displayed diffuse white matter compromise and poor intellectual outcome shortly after radiation treatment. There was evidence of subsequent growth of white matter structure, but stable intellectual insult. Conversely, in children treated with either surgery only or surgery and focal radiation to the tumor bed we observed less compromise of white matter early following treatment and no intellectual insult compared to healthy children. However, declines in intellectual function were evident for these children, though their performance remained within the average normative range. Overall, results suggest that early intervention is necessary to circumvent these deficits.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets