A preliminary examination of prolonged exposure therapy with iraq and afghanistan veterans with a diagnosis of posttraumatic stress disorder and mild to moderate traumatic brain injury

Authors: Wolf GK, Strom TQ, Kehle SM, Eftekhari A.

OBJECTIVE:  Preliminary examination of the effectiveness of prolonged exposure (PE) therapy for the treatment of posttraumatic stress disorder (PTSD) with Operation Enduring Freedom and Operation Iraqi Freedom Veterans who have experienced traumatic brain injury (TBI).
PARTICIPANTS: Ten Veterans with a history of mild to moderate TBI and chronic PTSD.
SETTING: Outpatient Mental Health/PTSD clinics and polytrauma centers at 2 VA medical centers.
MEASURES: Comprehensive evaluation that included clinical interview, neuropsychologic evaluation, and/or neuroimaging; Posttraumatic Stress Disorder Checklist and Beck Depression Inventory-Second Edition.
PROCEDURES: Standard implementation of the PE manual was used in all cases with slight adjustments to account for Veterans' residual cognitive deficits. Veterans completed between 8 and 18 sessions.
RESULTS: Veterans demonstrated significant reductions in total PTSD and depression symptoms from pre- to posttreatment. Within-group effect sizes were large.
CONCLUSIONS: These findings suggest that PE can be safely and effectively implemented with Veterans with PTSD, a history of mild to moderate TBI, and current cognitive impairment.

Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy

Authors: Stern RA, Riley DO, Daneshvar DH, Nowinski CJ, Cantu RC, McKee AC.

Chronic traumatic encephalopathy (CTE) has been linked to participation in contact sports such as boxing and American football. CTE results in a progressive decline of memory and cognition, as well as depression, suicidal behavior, poor impulse control, aggressiveness, parkinsonism, and, eventually, dementia. In some individuals, it is associated with motor neuron disease, referred to as chronic traumatic encephalomyelopathy, which appears clinically similar to amyotrophic lateral sclerosis. Results of neuropathologic research has shown that CTE may be more common in former contact sports athletes than previously believed. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, is responsible for neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and TDP-43 proteins. Given the millions of youth, high school, collegiate, and professional athletes participating in contact sports that involve repetitive brain trauma, as well as military personnel exposed to repeated brain trauma from blast and other injuries in the military, CTE represents an important public health issue. Focused and intensive study of the risk factors and in vivo diagnosis of CTE will potentially allow for methods to prevent and treat these diseases. Research also will provide policy makers with the scientific knowledge to make appropriate guidelines regarding the prevention and treatment of brain trauma in all levels of athletic involvement as well as the military theater.

Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide

Authors: Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, Fitzsimmons RP.

Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.

Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury

Authors: Davenport ND, Lim KO, Armstrong MT, Sponheim SR.

Mild traumatic brain injury (mTBI) due to explosive blast is common among military service members and often associated with long term psychological and cognitive disruptions. Little is known about the neurological effects of blast-related mTBI and whether they differ from those of civilian, non-blast mTBI. Given that brain damage from blasts may be diffuse and heterogeneous, we tested the hypothesis that blast mTBI is associated with subtle white matter disruptions in the brain that are spatially inconsistent across individuals. We used diffusion tensor imaging to examine white matter integrity, as quantified by fractional anisotropy (FA), in a group of American military service members with (n=25) or without (n=33) blast-related mTBI who had been deployed as part of Operation Iraqi Freedom or Operation Enduring Freedom. History of civilian non-blast mTBI was equally common across groups, which enabled testing of both blast and non-blast mTBI effects on measures sensitive to (1) concentrated, spatially consistent (average FA within a region of interest ), (2) concentrated, spatially variable (number of ROIs with low average FA), and (3) diffuse (number of voxels with low FA) disruptions of white matter integrity. Blast mTBI was associated with a diffuse, global pattern of lower white matter integrity, and this pattern was not affected by previous civilian mTBI. Neither type of mTBI had an effect on the measures sensitive to more concentrated and spatially consistent white matter disruptions. Additionally, individuals with more than one blast mTBI tended to have a larger number of low FA voxels than individuals with a single blast injury. These results indicate that blast mTBI is associated with disrupted integrity of several white matter tracts, and that these disruptions are diluted by averaging across the large number of voxels within an ROI. The reported pattern of effects supports the conclusion that the neurological effects of blast mTBI are diffuse, widespread, and spatially variable.

Characteristics of an Explosive Blast-Induced Brain Injury in an Experimental Model

Authors: de Lanerolle NC, Bandak F, Kang D, Li AY, Du F, Swauger P, Parks S, Ling G, Kim JH.

Mild traumatic brain injury resulting from exposure to an explosive blast is associated with significant neurobehavioral outcomes in soldiers. Little is known about the neuropathologic consequences of such an insult to the human brain. This study is an attempt to understand the effects of an explosive blast in a large animal gyrencephalic brain blast injury model. Anesthetized Yorkshire swine were exposed to measured explosive blast levels in 3 operationally relevant scenarios: simulated free field (blast tube), high-mobility multipurpose wheeled vehicle surrogate, and building (4-walled structure). Histologic changes in exposed animals up to 2 weeks after blast were compared to a group of naive and sham controls. The overall pathologic changes in all 3 blast scenarios were limited, with very little neuronal injury, fiber tract demyelination, or intracranial hemorrhage observed. However, there were 2 distinct neuropathologic changes observed: increased astrocyte activation and proliferation and periventricular axonal injury detected with β-amyloid precursor protein immunohistochemistry. We postulate that the increased astrogliosis observed may have a longer-term potential for the exacerbation of brain injury and that the pattern of periventricular axonal injury may be related to a potential for cognitive and mood disorders.

Factors Affecting Blast Traumatic Brain Injury

Authors: Kamnaksh A, Kovesdi E, Kwon SK, Wingo DL, Ahmed F, Grunberg NE, Long JB, Agoston D.

The overlapping pathologies and functional outcomes of blast induced TBI (bTBI) and stress-related neurobehavioral disorders like PTSD are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis, treatment, as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naïve rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I through C III animals exhibited increased anxiety but serum CORT levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated IFNγ and IL-6 levels in their amygdala (AD) and ventral hippocampus (VHC). GFAP levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in Iba1 and GFAP immunoreactivities as well as increased numbers of TUNEL+ cells in their VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors on the development of post-traumatic symptoms and to establish a differential diagnosis for PTSD and bTBI.


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