White Matter Abnormalities in Veterans With Mild Traumatic Brain Injury

Department of Child and Adolescent Psychiatry, Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands
American Journal of Psychiatry (Impact Factor: 12.3). 12/2012; 169(12):1284-91. DOI: 10.1176/appi.ajp.2012.12050600
Source: PubMed


It has been estimated that 10%-20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI.

DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy ("potholes") were used. Veterans also underwent psychiatric and neuropsychological assessments.

Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks.

Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.

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Available from: Ricardo E. Jorge, Aug 14, 2015
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    • "In addition, recent results in animal models and humans suggest that DTI indices in GM might reveal important information about mTBI, but most DTI analysis tools available today concentrate only on the analysis of the white matter (Budde et al. 2011; Bouix et al. 2013). Recent techniques have tried to address this problem by creating full brain subject-specific profiles of injury based on a reference atlas built from healthy subjects (Bouix et al. 2013; Kim et al. 2013; Mayer et al. 2014; Jorge et al. 2012; Davenport et al. 2015). This issue is even more interesting in military population with blast exposure where one could expect both subject specific abnormalities and a common pattern of injury from exposure to blast. "
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    ABSTRACT: Traumatic brain injury (TBI) remains one of the most prevalent forms of morbidity among Veterans and Service Members, particularly for those engaged in the conflicts in Iraq and Afghanistan. Neuroimaging has been considered a potentially useful diagnostic and prognostic tool across the spectrum of TBI generally, but may have particular importance in military populations where the diagnosis of mild TBI is particularly challenging, given the frequent lack of documentation on the nature of the injuries and mixed etiologies, and highly comorbid with other disorders such as post-traumatic stress disorder, depression, and substance misuse. Imaging has also been employed in attempts to understand better the potential late effects of trauma and to evaluate the effects of promising therapeutic interventions. This review surveys the use of structural and functional neuroimaging techniques utilized in military studies published to date, including the utilization of quantitative fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), volumetric analysis, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), positron emission tomography (PET), magnetoencephalography (MEG), task-based and resting state functional MRI (fMRI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). The importance of quality assurance testing in current and future research is also highlighted. Current challenges and limitations of each technique are outlined, and future directions are discussed.
    Brain Imaging and Behavior 09/2015; DOI:10.1007/s11682-015-9444-y · 4.60 Impact Factor
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    • "Recent DTI studies that have examined the impact of blast-induced mTBI on white matter integrity have reported mixed findings (Bazarian et al., 2013; Davenport et al., 2012; Jorge et al., 2012; Levin et al., 2010; Mac Donald et al., 2011). Whereas Mac Donald et al. (2011) reported that specific regions such as the cerebellum are impacted by blast, others have provided evidence for diffuse abnormalities in white matter not constrained to particular regions (Davenport et al., 2012; Jorge et al., 2012). Still other studies have not found a link between white matter abnormalities and blast-related mTBI using region-of-interest (ROI; Levin et al., 2010) or voxel-based (Bazarian et al., 2013) analyses. "
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    ABSTRACT: Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF Veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI-LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.
    Clinical neuroimaging 04/2015; 28. DOI:10.1016/j.nicl.2015.04.001 · 2.53 Impact Factor
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    • "h to characterize the complexity and heterogeneity of TBI pathophysiology . Novel imaging techniques need to be further developed to identify WM injury , neuroinflammation , and astrogliosis across different stages . A recent study reported that veterans with a history of mTBI could not be differentiated from those without TBI at the acute stage ( Jorge et al . , 2012 ) . However , several years after the trauma , veterans with a history of mTBI were found to have abnormal DTI results , highlighting the importance of identifying injury at the acute stage so that treatment can be provided to prevent further degeneration . In addition , a com - binational use of both molecular biomarkers and advanced i"
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    ABSTRACT: An improved understanding and characterization of glial activation and its relationship with white matter injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination after brain trauma. Traumatic brain injury (TBI) is a significant public healthcare burden and a leading cause of death and disability in the United States. Particularly, traumatic white matter (WM) injury or traumatic axonal injury has been reported as being associated with patients' poor outcomes. However, there is very limited data reporting the importance of glial activation after TBI and its interaction with WM injury. This article presents a systematic review of traumatic WM injury and the associated glial activation, from basic science to clinical diagnosis and prognosis, from advanced neuroimaging perspective. It concludes that there is a disconnection between WM injury research and the essential role of glia which serve to restore a healthy environment for axonal regeneration following WM injury. Particularly, there is a significant lack of non-invasive means to characterize the complex pathophysiology of WM injury and glial activation in both animal models and in humans. An improved understanding and characterization of the relationship between glia and WM injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination. GLIA 2014
    Glia 11/2014; 62(11). DOI:10.1002/glia.22690 · 6.03 Impact Factor
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