SPORTS SCIENCE (Quality Work, No Plagarism, A++)
LAGNIAPPE
Blast-induced_traumatic_brain_injury_and_post-traumatic_stress_disor....pdf
Section 1 Traumatic Brain Injury Chapter
3 Blast-induced traumatic brain injury and post-traumatic stress disorder Ankit I. Mehta, Gerald A. Grant, and Lawrence F. Marshall
Introduction “Only the dead have seen the end of war.” Plato
As modern warfare has been transformed with the use of improvised explosive devices (IEDs) resulting in blast injury, the medical community has been adapt- ing new treatment strategies. Despite a decreased mor- tality on the battlefield through improved mobilized medical units and armor, the devastation that soldiers suffer is prolonged beyond the battlefield especially in the setting of traumatic brain injury (TBI).
With the recent conflicts in Iraq and Afghanistan, a renewed interest in the physiological basis of TBI has provoked much discussion regarding the attribution of cause for symptoms surrounding blast injury [1]. Since the neurocognitive symptoms of TBI and post-traumatic stress disorder (PTSD) have significant overlap, it has been difficult to categorize patients [2]. The symptoms that overlap amongst these two entities are confounded by co-morbidities of depression, insomnia, fatigue, irritability, trouble concentrating, avoidance and hyperarousal.
The overlap between PTSD and TBI continues to be a subject of significant debate due to two main fac- tors: (1) an increased prevalence of blast injury in our troops returning from recent conflicts and (2) non- categorized screening criteria for soldiers. From a his- torical perspective, two different groups of medical professionals have dealt with these disease entities. PTSD has been treated by mental health professionals and is diagnosed at least 3 to 6 months after repeated, disturbing memories from situations that are reminis- cent of a stressful experience [3]. Mild blast TBI, in contrast, has been treated mostly by neurosurgeons and neurologists and is characterized by an alteration
in the level of consciousness or loss of consciousness for up to 30 minutes after injury [4]. Due to the clin- ical divide in management, there has been an impe- tus in the field to dissociate these diseases of TBI and acute stress disorder. One or both may contribute to the development of PTSD.
However, there have been multiple studies in the recent literature that have linked the disease entities of PTSD and mild TBI retrospectively. In one study, 44% of soldiers returning from the Iraqi war with mild TBI also met criteria for PTSD [5]. Mild TBI in another study doubled the risk of consequently devel- oping PTSD [6]. In screening for mild TBI in veter- ans, those who tested positive for TBI had a preva- lence of 85% with PTSD [7]. When 2525 US Army infantry soldiers were screened, 4.9% reported loss of consciousness (LOC), 10.3% had altered mental sta- tus and 17.2% had other injuries during deployment [5]. On further questioning of the patients who expe- rienced LOC, 43.9% met criteria for PTSD, compared to 27.3% with altered mental status, 16.2% with other injuries and 9.2% with no injuries. This study con- founds previous factors in determining the difference between mild TBI and PTSD.
Historical overview of blast injuries Many of the challenges in managing blast injury were recognized initially from the period of World War (WW) I. It was reported that the British Army phys- icians Drs Fred Mott and Gordon Holmes had diffi- culty distinguishing between physical brain injury and psychological trauma associated with blast injury [8]. In WWII, there continued to be controversy about the organic basis of psychological trauma. A group of clinicians believed no physical damage occurred
Traumatic Brain and Spinal Cord Injury, ed. Cristina Morganti-Kossmann, Ramesh Raghupathi, and Andrew Maas. Published by Cambridge University Press. C© Cambridge University Press 2012.
30 <i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
during blast injury, thus describing “shell shock” as a pure neuropsychological disorder, while another group found EEG changes in blast injury patients which were very similar to those seen in patients with closed head injuries [9]. This second group there- fore concluded that there were physical changes in the brain after blast injury which account for symp- toms. Interestingly, the neuropsychological role in blast injury continues to be questioned today despite our improved understanding of blast injury, TBI and PTSD, and with improved neuroimaging tools (i.e. computerized tomography (CT), magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and magnetoencephalography (MEG)).
Fuel-air explosives were introduced to warfare in the Vietnam and Korean wars. As improvements in weapons and protective measures have developed, the patterns of injuries have evolved from the Vietnam era to the current conflicts in Afghanistan and Iraq [10]. The trend of blast injuries related to fragments has increased in prevalence in comparison to bullet injuries from the Vietnam era. The ratio of injuries in Vietnam of fragment to bullet was 5:3. In contrast, the Iraqi war in 1991 had reported rates of 19:1 [11] and 8:1 [12]. When assessing the pattern of injuries to the head and neck from fragments and bullets, there was a decrease in modern warfare due to an improvement in armor and head protection. The rate of head and neck injuries was 43% during the Vietnam War, which dropped to 16–21% in Afghanistan and Iraq in 2003 [13, 14]. It has been postulated that this drop was due to improvements in armor both on vehicles and on sol- diers. IEDs have been responsible for one-third of all American deaths in Iraq. The US military as of 2005 invested $3.3 billion dollars in IED countermeasures including armor [15] and preventive measures due to the increased morbidity from blast injury due to IEDs.
Mechanism of blast injury An explosive blast produces a transient pressure wave that transcends through a medium such as water and air after the detonation of an explosive device. There are peaks and troughs of pressure that vary from a maximum pressure to a vacuum transferring expand- ing gas into thermal, mechanical, electromagnetic and radiation energy to the surrounding space. Forces on the soldier involved with blast injury are determined not only by the peak pressure but also by the length of
time that the injury is sustained. The peak overpres- sure and range determine survival in the vicinity of an explosion [16].
Body armor developed for protection of soldiers could mitigate penetrating ballistic injury and reduce secondary blast injury. However, armor may not have provided the same protection to the blast overpressure causing primary blast injury. The pressure differential is thought to affect air-filled organs and air-fluid inter- faces more significantly where the differential of den- sity is the greatest. However, the clinical experience has suggested that the brain is uniquely more vulnerable to blast-induced injury than the bowels and lungs. This finding is surprising and the mechanism behind this increased susceptibility remains unknown. The blast injury sustained to the brain is more likely to cause axonal swelling and edema rather than hemorrhage. In civilian TBI, there is a 3–10% frequency of hemorrhage on CT scans although the population seen at Level I or II trauma centers markedly will affect the rate of posi- tive CTs seen in patients following a TBI [16]. Another unique characteristic of blast injury is that in animal models, neurons and astrocytes develop scarring due to a re-entry into the cell cycle. Neurons die upon this re-entry via caspase-dependent apoptosis. Astrocytes proliferate as they re-enter the cell cycle and produce gliosis [17]. After blast injury in animal models, the brain demonstrates changed gene expression of regu- latory proteins of cell cycling [18, 19].
Prevalence of traumatic brain injury There has been an increasing prevalence of TBI among soldiers serving in Afghanistan and Iraq. Overall, one- quarter of evacuated troops from Iraq and Afghanistan suffer head and neck injuries including severe brain trauma [7, 14, 24]. The causality of TBI is asso- ciated with an increased use of IEDs but also an increased aptitude amongst clinicians in diagnosis and screening. Two-thirds of war zone evacuees to Wal- ter Reed Army Medical Center in 2006 had blast injuries [20]. In Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF), explosive blasts account for 60% of casualties [21]. Another study found IEDs responsible for 88% of mili- tary injuries treated at the Echelon II medical center in Iraq; of which 47% involved head injuries [22]. A con- tinued trend was noted in a third study that demon- strated 97% of injuries to a Marine unit in Iraq were due to explosions (32% mines, 65% IEDs) where 53%
31<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
Figure 3.1. Blast-induced TBI may result in penetrating fragments of any size which can penetrate the skull. Axial CT scans are shown from three different patients who suffered a blast-induced penetrating brain injury.
involved the head and neck [23]. Members of an Army unit (n = 3973) that served in Iraq were assessed for TBI. The study found 22.8% of soldiers serving in a Brigade Combat Team suffered clinically confirmed TBI according to the American Congress of Rehabil- itation Medicine mild TBI criteria [24].
Defining traumatic brain injury Traumatic brain injury (TBI) is a largely generalized term that refers to a spectrum of injury from a con- cussion to severe traumatic brain injury. Mechanism is important to the definition of a TBI. TBI has been clas- sically defined as penetrating TBI (pTBI) and closed TBI (cTBI); however, in light of the usage of IEDs, a third category of blast TBI (bTBI) has emerged. Penetrating TBI involves a foreign object penetrat- ing into the bony skull, traversing the parenchyma of the brain causing cavitation injury. Closed TBI involves a disruption of neurological function from brain motion and deformation. cTBI induces inflam- mation and the release of free radicals throughout the brain parenchyma.
Blast TBI occurs from physical forces associated with pressure waves however, it also incorporates com- ponents of cTBI and pTBI [21] (Figures 3.1 and 3.2). The Center for Disease Control defines blast injury as primary, secondary, tertiary, quaternary and quinary (Figure 3.3) [25]. Primary blast injury occurs from the physical forces from the explosion where a blast wave induces changes in the pressure with high pressure followed by a vacuum. Barotrauma associated with primary blast injury causes damage
to vasculature and neurons and perforated tympanic membranes [26]. Secondary blast injury involves blast injury putting shrapnel in motion causing penetrating and blunt brain injuries. The secondary blast injury is dependent upon the surrounding environment around the blast, where debris and weapon casing are turned into projectiles. Tertiary blast injury places the sol- dier or patient in motion where they develop coup and countercoup injuries from the brain striking the fixed calvarium, causing damage. These inertial forces of ter- tiary injury could create subdural hemorrhages at the points of impact of the brain against the calvarium. Quaternary blast injury includes chemical and ther- mal burn injuries. Quinary blast injury is due to toxic byproducts from the blast, which include radiation, bacteria, metals and gases.
The clinical spectrum for bTBI ranges from a period of confusion to severe coma (Table 3.1). Mild bTBI is defined as a brief (�5 minutes) loss of con- sciousness or awareness. The Glasgow Coma Scale (GCS) for these patients is 13 to 15. Mild TBI can lead to symptoms of headache, confusion, amnesia, difficulty concentrating, mood alteration, sleep distur- bance and anxiety [27]. These symptoms are short- lived and usually resolve in a few hours or days. However, approximately 15% of patients develop a post-concussive syndrome that can present days later and last with only modest late improvement [27, 28]. Therapy for mild bTBI involves reassurance and treat- ing the symptoms specifically. Thereby, patients with headaches are given anti-migraine medication and non-narcotic analgesics. Symptoms of depression are treated with anti-depressants. Moderate bTBI involves
32<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
Table 3.1. Blast TBI varies from mild to severe with associated symptoms. Therapy for mild bTBI includes strategies to treat the clinical symptoms. Neurosurgeons care for moderate and severe bTBI. In severe bTBI, neurocritical care is needed with intracranial pressure monitoring
Blast TBI GCS Symptoms Therapy
Mild 14–15 � Brief (�5 min) LOC � Headache, confusion, amnesia, difficulty concentrating, mood alteration, anxiety, sleep disturbance
� Symptoms resolve in few hours or days � Develop post-concussive syndrome
� Reassurance � Anti-migraine medications for headaches
� Non-narcotic analgesics
Moderate 9–13 � Prolonged LOC and/or neurological deficit � Mild also develop post-concussive syndrome
� Support at a combat hospital � May require neurosurgical care
Severe �8 � Obtunded or comatose � Significant neurological injury � Radiographic abnormal injury: skull fracture, intracerebral hemorrhage, early diffuse cerebral edema, subarachnoid hemorrhage
� Intubation-airway protection � Neurocritical/neurosurgery care � Intracerebral pressure monitoring
Figure 3.2. Traumatic brain injury has been classically defined as penetrating TBI (pTBI) and closed TBI (cTBI). Primary blast TBI (bTBI) is the third category and has components of pTBI and cTBI in addition to damage caused by pressure waves. See plate section for color version.
a GCS score of 9 to 12, and involves patients who have prolonged loss of consciousness and/or a neurologic- al deficit [29]. Patients should be moved to a combat hospital and may require ongoing neurosurgical care. These patients might also develop a post-concussive syndrome like mild bTBI.
Severe bTBI causes a patient to be comatose or obtunded with a GCS of 8 or less. Physiologically there is often diffuse cerebral edema and hyperemia with a loss of cerebral autoregulation. There is a sig- nificant neurological injury involving radiographic changes which include skull fracture, ICH, early
diffuse cerebral edema and subarachnoid hemorrhage (SAH) [29]. Treatment involves neurocritical care, pri- marily protecting the airway with intubation and sub- sequently using intracranial pressure (ICP) monitor- ing. The SAH involved with severe bTBI indicates a more severe injury and an increased risk of secondary neurological injury from cerebral vasospasm [30]. Mil- itary neurosurgeons are more apt to perform a decom- pressive craniectomy for severe bTBI than cTBI or pTBI [10, 16]. Decompressive craniectomy for severe bTBI can quickly decrease ICP and can ease trans- port of soldiers to tertiary medical centers that have
33<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
Figure 3.3. Blast TBI causes primary injury through a blast wave with a sinusoidal wave of high pressure followed by a vacuum. This causes barotrauma and perforation of the tympanic membranes. Secondary bTBI results from penetrating shrapnel entering the cranium. Tertiary blast injury causes blunt injury resulting in subdural hemorrhages after soldiers are sent into motion from the blast. Quaternary blast injury includes chemical and thermal burn injuries. Quinary blast injury is due to toxic byproducts from the blast that include radiation, bacteria, metals and gases. See plate section for color version.
dedicated neurointensive care units. In severe TBI, there is a prolonged recovery and often it is incomplete. A significant number of patients do not live beyond 1 year [10].
Screening for TBI in the military populations Part of the difficulty in determining the presence of TBI has been in the screening process to diagnose particularly mild TBI. The difficulty of screening for TBI is inherent due to the subjectivity in self-report and tendency for patients to telescope, and only report the most severe or recent experience [25]. Furthermore, self-reporting TBI through a structured
interview and questionnaire has inherent pitfalls, with the patient having to acknowledge they were injured. In a single questionnaire of prisoners who suffered a TBI, only 19% of TBIs were identified by structured interviews [26]. The military has been using the War- rior Administered Retrospective Casualty Assessment Tool (WARCAT) to assess soldiers for TBI through clinical interviews about the injury history, somatic symptoms (headache, dizziness) and neuropsychiatric symptoms (memory, irritability) after an injury event that is followed by altered consciousness [24]. A stan- dardized initial evaluation of concussion performed by combat medics involves using the Military Acute Concussion Evaluation (MACE), a three-part exam- ination to assess mild TBI [27]. Preliminary results
34<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
assessed in injured and uninjured athletes demon- strate a sensitivity and specificity of 94% and 76%, respectively. The increased sensitivity but decreased specificity makes this assessment a useful screening tool in the field. However, there are issues surrounding military culture where there is a reluctance of soldiers to report symptoms due to concern of being relieved from military missions [28]. The VA screen requires that the individual had symptoms consistent with a concussion at the time of the event and is still having some of those symptoms which are attributable to the putative TBI. The Post Deployment Health Assessments (PDHA) ask about TBI symptoms but do not require that the soldier has persistent symptoms, in contrast to the Defense Veterans Brain Injury Center TBI Screening Tool, which asks about current symptoms which might be related to a possible head injury or concussion. Because of the perceived lack of reliability in screening and difficulty validating retrospectively, there is now a concerted effort by interdisciplinary teams to administer structured interviews to better diagnose TBI retrospectively using a combination of the credible account of the traumatic event, post-traumatic signs and symptoms and/or neurological changes. The military and civilian surveillance instruments for TBI screening agree on the core components of mild TBI, which included a loss of consciousness for less than 30 minutes or an alteration or disturbance in consciousness manifested by confusion or disorientation as well as lack of mem- ory of the events after the injury for less than 24 hours.
Defining post-traumatic stress disorder Post-traumatic stress disorder occurs through behav- ioral symptoms of autonomic hyperactivity, avoidance, and “flashbacks” or re-experiencing from an origin of a threatening traumatic event that caused fear or helplessness [31]. More specifically, the criteria for diagnosis according to the DSM IV specify 4 weeks or more of symptoms causing distress or impairment from social, occupational or other areas of function- ing [31]. Among soldiers returning from OIF/OEF in the recent conflicts of Iraq and Afghanistan, there is a prevalence of PTSD that ranges from 5% to 20% [32].
The pathophysiology of PTSD has been thought to be attributable to an increased activation of the amygdala by stimuli that create an acute and chronic stress response [33]. The amygdala mediates mem- ory through consolidating emotional response with
spatial learning from the hippocampus. It is thought that the normal threshold for amygdala activation decreases after PTSD, causing smaller stimuli to create fear responses [1].
Consequencesoftraumaticbraininjury
Mortality An increasing body of evidence suggests that trau- matic brain injury reduces life expectancy. This is understandable given the mechanisms beyond blast injury inducing a pathophysiological process that lasts through patients’ lifetime. One year after moderate or severe TBI, 2178 patients in a 2004 study had a reduction of 7 years in life expectancy [34]. Follow-up studies in 2006 found that patients who lived beyond a year after TBI had the following causes associated with death: 37 times more likely to die of seizures, 12 times more likely to develop sepsis, 3 times more likely to develop respiratory disorders, and 4 times more likely to develop pneumonia [35]. The cause of death of patients with TBI from a retrospective chart review was shown as: 49 times more likely to die from aspiration pneumonia, 22 times more likely to die of seizures, 3 times more likely to die from suicide and 2.5 times more likely to die from digestive disorders [34]. Mild TBI also reduces life expectancy; however, to a lesser degree than moderate and severe TBI. In a population-based, retrospective study of 1448 patients with TBI, the mortality risk-ratio was 5.29 in moderate and severe TBI after a year, and 1.33 in mild TBI compared to the general population. In this study, patients with a mild TBI had an increased incidence of seizures, sleep disorders, neurodegen- erative diseases, neuroendocrine dysregulation and psychiatric diseases. Since there are a larger number of mild TBI patients than moderate and severe TBI patients, this is a real and considerable increase in mortality [36].
Epilepsy TBI accounts as a cause of 5% of epilepsy in the general population [37]. Due to blast injury causing multiple modalities of TBI, there is an increased prevalence of epilepsy. More specifically, patients with pTBI have higher epilepsy rates than cTBI. In a study of 309 patients with moderate to severe TBI, 9% needed treatment for epilepsy in a 24-year post-injury follow-up [38]. Initial GCS score was associated with
35<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
late post-traumatic seizures at 24 months: GCS score of 3 to 8, 16.8%; GCS score of 9 to 12, 24.3%; and GCS score of 13 to 15, 8.0%. After a traumatic event, the first-time epileptic event could occur as far as 12 years post event as noted in a case report [39]. The trauma literature has consistently shown that post-traumatic epilepsy has a higher propensity when dural penetra- tion is noted by bone or shrapnel, parietal contusions, subdural hematoma and increased midline shift. There has been a recent report where 1221 Vietnam War veterans were followed longitudinally after primarily penetrating head injury. Interestingly 12.6% of the 87 patients that developed seizures developed their seizures more than 14 years after the injury. Therefore, patients after war injury have a prolonged high risk of seizures decades after injury [40].
Sleep disorders On a subjective analysis, both PTSD and TBI can result in disorders of sleep, making categorizing the cause of the symptomology difficult. In TBI patients, 70% of patients have subjective claims of sleep dis- turbance [41]. Interestingly on objective analysis of polysomnography, at 3 years post-injury 45% of 71 patients with TBI had a disturbed sleep [42]. In deter- mining the etiology of the disturbed sleep, TBI patients had an increased incidence of obstructive sleep apnea [43]. The specific etiology of this is unknown, but may be associated with ultrastructural changes in the brain- stem [44].
Substance abuse A higher incidence of substance abuse is noted in patients after TBI and PTSD. There was an 11.7% rate of alcohol abuse or dependence that was noted in a group of 60 patients who were followed up to 30 years post-injury [45]. This finding was in line with larger studies of 361 patients with TBI where 14% had alco- hol abuse or dependence and 10.9% developed drug dependence [46]. Interestingly, more patients devel- oped substance abuse issues at 5 years post-injury than at 2 years post-injury, suggesting a more chronic devel- opment of substance disorders [47]. All of these stud- ies suggest an increased risk of substance abuse; how- ever, the question arises whether the subpopulation that develops TBI symptoms had pre-existing sub- stance abuse disorders prior to the injury. Since these are retrospective observational studies, it is difficult to answer the causality of these disorders.
Figure 3.4. The symptoms associated with PTSD, mTBI and depression overlap considerably, thereby making diagnosis difficult in patients.
Stress Stress is a co-morbidity associated with both TBI and PTSD. There has been evidence that the precondition- ing and protective effect of repeated low-level repeated stresses decreases the development of PTSD [48]. When animals had induced heat stress over repeated intervals they had a quicker functional recovery from a primary blast injury. This provides some insight into the benefit of preconditioning.
Depression Depression is a common co-morbidity with both PTSD and TBI (Figure 3.4). Major depressive disorder is characterized by sadness with somatic complaints of decreased appetite, change in sleep patterns, suici- dal thoughts, inability to concentrate and fatigue [31]. TBI is associated with an increased risk of depression. Major depressive disorder is significantly associated with TBI, with an odds ratio of 1.63 [5]. In troops returning from Iraq who suffered from mild TBI, defined with loss of consciousness (LOC) or altered consciousness, there was an increased risk of major depression compared to other injury with LOC (22.9% vs. 6.6%; p � 0.001) but not with altered consciousness (8.4% vs. 6.6%; p = 0.39).
Biomarkers of blast injury Since there is such a clinical overlap between PTSD and TBI, the Holy Grail in the field has been to deter- mine a biomarker to discriminate TBI from PTSD. An ideal biomarker would be sensitive enough to pick up patients on routine screening but specific enough to prevent false positives. In addition, it would be ideal to have an easy biomarker that could be obtained in a combat hospital where soldiers can be adequately treated.
36<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
Current imaging modalities such as CT scan are inadequate since in mild and moderate TBI imaging is negative in most cases [49]. In the battlefield, more advanced neuroimaging proves to be almost impossi- ble to obtain in blast injury patients. Therefore a blood- based biomarker using human serum to detect a spe- cific protein has been heavily investigated. A current serum biomarker, S100�, has been studied in the set- ting of civilian TBI. S100� is a nonspecific marker since it is expressed in Schwann cells. S100� has a relatively short half-life of 30 minutes to 1 hour and is therefore an early marker of TBI [50]. There have been studies that demonstrate a correlation between S100� and the severity of traumatic head injury on the Marshall CT classification [51–53]. Despite being correlative of severity of TBI, S100� has been a poor predictor of outcomes by itself, especially for mild TBI [54].
Another biomarker that has recently gone out of favor is neuron-specific enolase (NSE). NSE despite its name is not specific, with expression as well in non- neuronal tissue such as platelets and red blood cells. In addition is has a long half-life of 20 hours, which makes it not as useful alone as an acute biomarker for neuro- trauma [55]. Studies have demonstrated that NSE and S100� in combination correlated with mortality and were higher in the first hours post-injury in patients with poor outcomes compared to good outcomes [50, 56].
A more specific marker that is in the CNS is glial fibrillary acidic protein (GFAP). It has been found to be a predictor of mortality in TBI [53, 57]. GFAP is a monomeric intermediate filament protein of astro- cytes. When analyzing all three biomarkers (S100�, NSE, GFAP) for a group of 85 patients after severe TBI, the factors are strongly predictive of poor outcome, with odds ratios of 5.12 [S100�], 8.82 [GFAP], and 3.95 [NSE]. All of these biomarkers may be elevated in severe TBI but have been shown to have limited or no application in less severe injuries. Other potential proteins that are currently under investigation include c-Tau, �II-spectrin breakdown products and NMDA fragments. The results of these as predictors for mild TBI are not as encouraging. c-Tau has been shown to be a poor predictor for 3-month outcome after mild TBI [54]. Therefore, further research is necessary to assess the presence of mild TBI since thus far there has not been a reliable panel of biomarkers available which in combination are both sensitive and specific enough for clinical use.
Clinical signs may also serve as markers of blast injury. An interesting study has assessed the other clin- ical effects of blast injury and correlated them with neurological injury. As stated previously, primary blast injury induces atmospheric pressure changes to cause damage to air-filled organs and vulnerable structures such as the tympanic membrane. The tympanic mem- brane is vulnerable to blast exposures since a relatively low pressure differential is needed to cause damage to the structure. In a study of 210 US soldiers, the inci- dence of loss of consciousness and tympanic mem- brane perforation was assessed. The findings of the study demonstrated significant association between loss of consciousness and tympanic membrane per- foration, with a relative risk of 2.76 [58]. In addi- tion, the authors concluded that there is a high index of neurological injury for patients with bilateral tym- panic membrane perforation which can be easily diag- nosed in the field. The caveat is that a blast-induced TBI might be underestimated since we know from the sports literature that patients do not necessarily need to lose consciousness to have a concussion.
Neuroimaging of blast injury A head CT scan is the standard of care neuroimag- ing tool in the assessment of blast injury victims. CT scans can diagnose some of the effects of blast injury including shrapnel embedded in the skull, subdural hemorrhage, epidural hemorrhage, skull fractures and subarachnoid blood. CT scans are easily accessible to both military personnel and civilians. Despite 85% of patients with TBI having normal CT scans, 15% of this group have symptoms of blast injury that last from months to years after the time of injury [59] and may be associated with permanent neuropsychological sequelae in a subset of these.
In civilian TBI, magnetic resonance imaging (MRI) has been the modality of choice to assess patients with ongoing clinical symptoms but with a negative CT scan. The MRI images have been noted to identify 50% more pathological lesions than CT scan alone, espe- cially on fluid-attenuation inversion recovery (FLAIR) and T2 weighted sequences that demonstrate non- hemorrhagic contusions and diffuse axonal injury (DAI) [60]. However, MRI findings have not corre- lated with neurological outcomes associated with TBI despite an increased ability to detect pathology [61].
More advanced imaging modalities have been used mostly for research purposes. Positron emission
37<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
tomography (PET) and single-photon emission com- puterized tomography (SPECT) measure cerebral glu- cose metabolism and cerebral blood flow, respectively, thereby giving investigators insight into the patho- physiology of TBI.
Proton MR spectroscopy (MRS) has identified an increase in lactate concentrations after TBI that has been found to clinically correlate with poor clinical outcomes and neurophysiological symptoms [62]. MRS has been shown to indicate cellular injury with increases in N-acetylaspartate (NAA) and choline in areas that appear normal on MRI and CT scans [63]. The increased sensitivity of MRS towards cellular damage provides some encouraging data from a research perspective.
There have been certain imaging biomarkers that have shown differences in the disease entities such as functional neuroimaging. In patients with PTSD, the amygdala and insular cortex have increased activation [64]. In contrast, in TBI patients the orbital prefrontal cortex and subcortical white matter were more vul- nerable to hyperemia. This means of determination between the disease entities is not feasible immediately after injury, especially in combat medical units, and at this time it is still under investigation.
Diffusion tensor imaging (DTI) is used to assess white matter tracts and can demonstrate lesions that correlate with a decreased cognitive speed of process- ing [65]. DTI uses Brownian motion of water through tissues distinguishing microstructure through diffu- sivity [66]. By understanding the cognitive function associated with lesions in the white matter tracts, clinicians can determine what deficits blast injury patients will suffer. DTI has demonstrated white mat- ter changes especially within the thalamus in blast- related TBI patients compared to TBI patients and nor- mal controls [67].
Subarachnoid hemorrhage due to TBI can induce vasospasm after severe TBI. At the National Naval Medical Center, of soldiers who were evacuated and underwent cerebral angiography in 2003–2005, 47% developed vasospasm [30]. CTA and TCDs are sensi- tive in assessing vasospasm as well, and the capabilities for obtaining a CTA can be utilized at the same time as a CT. In cases of severe TBI, vascular imaging through CTA is indicated to provide therapy and management for patients with potential vasospasm.
Imaging modalities of CT and MRI are not sensi- tive enough to pick up changes associated with mild TBI. Encouraging preliminary data using MEG scans
may potentially give insight into patients’ symptoms with mild TBI. MEG is an imaging modality that meas- ures the magnetic signal due to neuronal activation, providing accurate localization and resolution. Injured tissue from TBI or other causes creates delta waves (1– 4 Hz) that can be differentiated from neuronal activ- ity at 8 Hz [68]. In a small group of patients (n = 10), MEG scans have been shown to be more sensitive than DTI in detecting neuronal damage of TBI, with better representation of symptoms associated with changes [69]. A study in patients with post-concussive symp- toms after mild TBI demonstrated that 45% of patients had abnormal MEG scans compared to 20% with EEG and 20% with MRI scans. When using the modali- ties of MEG and MRI in combination, 65% of patients with post-concussive symptoms were detected [70]. The data are encouraging, but larger studies need to be completed and accessibility of MEG scanners needs to be improved to implement this neurodiagnostic strat- egy for troops with blast injury.
A recent study demonstrated how DTI could detect traumatic axonal injury in patients with blast-related TBI. Of 63 patients with mild TBI after blast injury who produced DTI images within 90 days after injury, 18 patients had abnormalities seen on DTI [71]. DTI after blast injury was significantly associated with abnormalities in the middle cerebral peduncles (p � 0.001), cingulum bundles (p = 0.002) and right orbitofrontal white matter (p = 0.007) [71]. These data were encouraging and could eventually constitute a biomarker but the authors emphasize that the diagno- sis of TBI is clinical since not all of the blast injury patients developed abnormalities on DTI.
Personal protective equipment (PPE) for TBI There have been advances in personal protective equipment (PPE) for TBI that have dramatically increased survival rates beyond previous conflicts [21, 72]. The advanced combat helmet (ACH), along with improved medical care on the field, has been associ- ated with dramatically increased survival among sol- diers in current conflicts. Despite extensive research regarding ACH design to withstand blunt injury and penetrating injury, there has been a lack of evidence of ACH efficacy for mitigating blast concussive injury [73]. As explained above, blast injury induces pressure differentials that have not been effectively tested with usage of an ACH. A recent stimulation suggested that a
38<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
helmeted head had a wave-focused effect in space between the head and helmet creating a higher pres- sure differential than an unhelmeted head [73, 74]. This is a computer simulation that lacks padding in the helmet and lacks realistic geometric configurations [73].
Researchers at MIT and the Defense and Veter- ans Brain Injury Center utilized the Full Head Model to determine the intensity of stress waves in brain tissues after exposure to blast waves [75]. Using a finite-element model of 10 atm of overpressure for the blast wave, the authors compared brain stress waves of an unhelmeted head, a head with an ACH and a head with an ACH with face shield. In contrast to previous simulations, the model demonstrated that when comparing a head with an ACH to an unhel- meted head, there is a slight decrease in stress in the helmeted head. Interestingly, the combination of an ACH with a facemask impeded direct transmission of stress to the intracranial cavity, thereby decreas- ing intracranial stress [73]. This computational model suggests that adding a facial mask to an ACH could be a possible strategy for mitigating concussion after blasts.
Future advances in PPE will need to be tested with more advanced computational models that account for forces delivered during blast injuries. As materials improve to help reduce blast pressures they can be ade- quately tested in these models before implementation on troops in the field.
Future directions Blast injury accounts for a high degree of morbidity and mortality in recent conflicts in both operations in Afghanistan and Iraq. Blast injury-induced TBI is the most prevalent injury suffered by troops. Major ques- tions and issues have been raised in the management of blast injury including how to diagnose it, biomarkers of injury, neuroimaging, protective measures and the consequences from blast injury. The important ques- tion of diagnosis is critical when differentiating blast injury causing TBI versus PTSD since the symptoms overlap considerably. Co-morbidities also cloud our ability to discriminate these injuries. As neuroimaging and biomarkers have an increased ability to determine neuronal damage, TBI diagnosis after blast injury is increasing. The future of blast injury lies in our ability of diagnosis, and the practical treatment of its cogni- tive and behavioral sequelae.
Secondarily, using the information that is present in diagnosis, protective measures can be used to pre- vent injuries from occurring. We hope that through advanced computer simulations and improved materi- als that prevent the different types of injury sustained from a blast, veterans will have an improved mortality and morbidity.
References 1. McAllister TW, Stein MB. Effects of psychological and
biomechanical trauma on brain and behavior. Ann NY Acad Sci 2010;1208:46–57.
2. Stein MB, McAllister TW. Exploring the convergence of posttraumatic stress disorder and mild traumatic brain injury. Am J Psychiatry 2009;166(7):768–76.
3. Boals A, Schuettler D. PTSD symptoms in response to traumatic and non-traumatic events: the role of respondent perception and A2 criterion. J Anxiety Disord 2009;23(4):458–62.
4. Warden DL, French L. Traumatic brain injury in the war zone. New Engl J Med 2005;353(6):633–4.
5. Hoge CW, et al. Mild traumatic brain injury in U.S. soldiers returning from Iraq. New Engl J Med 2008;358(5):453–63.
6. Schneiderman AI, Braver ER, Kang HK. Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent postconcussive symptoms and posttraumatic stress disorder. Am J Epidemiol 2008;167(12):1446–52.
7. Hill JJ, 3rd, Mobo BH, Jr., Cullen MR. Separating deployment-related traumatic brain injury and posttraumatic stress disorder in veterans: preliminary findings from the Veterans Affairs traumatic brain injury screening program. Am J Phys Med Rehab/Association of Academic Physiatrists 2009;88(8):605–14.
8. Mott FW. The Chadwick Lecture on mental hygiene and shell shock during and after the war. BMJ 1917;2(2950):39–42.
9. Kocsis JD, Tessler A. Pathology of blast-related brain injury. J Rehab Res Dev 2009;46(6):667–72.
10. Rustemeyer J, Kranz V, Bremerich A. Injuries in combat from 1982–2005 with particular reference to those to the head and neck: a review. Brit J Oral Maxillofacial Surg 2007;45(7):556–60.
11. Carey ME. Analysis of wounds incurred by U.S. Army Seventh Corps personnel treated in Corps hospitals during Operation Desert Storm, February 20 to March 10, 1991. J Trauma 1996;40(3 Suppl): S165–9.
39<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
12. Burkle FM, Jr., et al. Emergency medicine in the Persian Gulf War–Part 3: battlefield casualties. Ann Emerg Med 1994;23(4):755–60.
13. Montgomery SP, Swiecki CW, Shriver CD. The evaluation of casualties from Operation Iraqi Freedom on return to the continental United States from March to June 2003. J Am Coll Surgeons 2005;201(1):7–12; discussion 12–3.
14. Xydakis MS, et al. Analysis of battlefield head and neck injuries in Iraq and Afghanistan. J Am Acad Otolaryngology-Head Neck Surgery 2005;133(4): 497–504.
15. Stuhmiller JH, Stuhmiller LM. A mathematical model of ventilation response to inhaled carbon monoxide. J Appl Physiol 2005;98(6):2033–44.
16. Youmans JR, Winn HR. Youmans Neurological Surgery, 6th ed. Philadelphia, PA: Saunders/Elsevier; 2011.
17. Cernak I, et al. Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 2005;4(9):1286–93.
18. Cernak I. Animal models of head trauma. NeuroRx J Am Soc Exp NeuroTherapeut 2005;2(3):410–22.
19. Natale JE, et al. Gene expression profile changes are commonly modulated across models and species after traumatic brain injury. J Neurotrauma 2003;20(10): 907–27.
20. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehab 2006; 21(5):398–402.
21. Ling G., et al. Explosive blast neurotrauma. J Neurotrauma 2009;26(6):815–25.
22. Murray CK, et al. Spectrum of care provided at an echelon II Medical Unit during Operation Iraqi Freedom. Military Med 2005;170(6):516–20.
23. Gondusky JS, Reiter MP. Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanized battalion during Operation Iraqi Freedom II. Military Med 2005;170(6):546–9.
24. Terrio H, et al. Traumatic brain injury screening: preliminary findings in a US Army Brigade Combat Team. J Head Trauma Rehab 2009;24(1): 14–23.
25. Centers for Disease Control and Prevention. Explosions and Blast Injuries: A primer for clinicians. Atlanta, GA: CDC; 2006.
26. DePalma RG, et al. Blast injuries. New Engl J Med 2005;352(13):1335–42.
27. Ling G, Maher C. U.S. neurologists in Iraq: personal perspective. Neurology 2006;67(1):14–7.
28. Ryan LM, Warden DL. Post concussion syndrome. Int Rev Psychiatry 2003;15(4):310–6.
29. Ling GS, Marshall SA. Management of traumatic brain injury in the intensive care unit. Neurol Clin 2008;26(2):409–26, viii.
30. Armonda RA, et al. Wartime traumatic cerebral vasospasm: recent review of combat casualties. Neurosurgery 2006;59(6):1215–25; discussion 1225.
31. American Psychiatric Association Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, 4th ed. Washington DC: American Psychiatric Association; 2000.
32. Ramchand R, et al. Disparate prevalence estimates of PTSD among service members who served in Iraq and Afghanistan: possible explanations. J Traumatic Stress 2010;23(1):59–68.
33. Bremner JD. Neuroimaging in posttraumatic stress disorder and other stress-related disorders. Neuroimag Clin North Am 2007;17(4):523–38, ix.
34. Harrison-Felix CL, et al. Mortality over four decades after traumatic brain injury rehabilitation: a retrospective cohort study. Arch Phys Med Rehab 2009;90(9):1506–13.
35. Harrison-Felix C, et al. Causes of death following 1 year postinjury among individuals with traumatic brain injury. J Head Trauma Rehab 2006;21(1): 22–33.
36. Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma 2010;27(8):1529–40.
37. Hauser WA, Annegers JF, Kurland LT. Prevalence of epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia 1991;32(4):429–45.
38. Yasseen B, Colantonio A, Ratcliff G. Prescription medication use in persons many years following traumatic brain injury. Brain Injury 2008;22(10): 752–7.
39. Aarabi B, et al. Prognostic factors in the occurrence of posttraumatic epilepsy after penetrating head injury suffered during military service. Neurosurg Focus 2000;8(1):e1.
40. Raymont V, et al. Correlates of posttraumatic epilepsy 35 years following combat brain injury. Neurology 2010;75(3):224–9.
41. McLean A, Jr., et al. Psychosocial functioning at 1 month after head injury. Neurosurgery 1984;14(4):393–9.
42. Masel BE, et al. Excessive daytime sleepiness in adults with brain injuries. Arch Phys Med Rehab 2001;82(11):1526–32.
43. Castriotta RJ, et al. Prevalence and consequences of sleep disorders in traumatic brain injury. J Clin Sleep Med 2007;3(4):349–56.
40<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Chapter 3: Blast-induced traumatic brain injury
44. Wilde MC, et al. Cognitive impairment in patients with traumatic brain injury and obstructive sleep apnea. Arch Phys Med Rehab 2007;88(10):1284–8.
45. Koponen S, et al. Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study. Am J Psychiatry 2002;159(8):1315–21.
46. Silver JM, et al. The association between head injuries and psychiatric disorders: findings from the New Haven NIMH Epidemiologic Catchment Area Study. Brain Injury 2001;15(11):935–45.
47. Olver JH, Ponsford JL, Curran CA. Outcome following traumatic brain injury: a comparison between 2 and 5 years after injury. Brain Injury 1996;10(11): 841–8.
48. Shein NA, Horowitz M, Shohami E. Heat acclimation: a unique model of physiologically mediated global preconditioning against traumatic brain injury. Prog Brain Res 2007;161:353–63.
49. Svetlov SI, et al. Biomarkers of blast-induced neurotrauma: profiling molecular and cellular mechanisms of blast brain injury. J Neurotrauma 2009;26(6):913–21.
50. Herrmann M, et al. Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography. J Neurotrauma 2000;17(2):113–22.
51. Marshall LF, et al. The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma 1992;9(Suppl 1): S287–92.
52. Berger RP, et al. Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurgery 2005;103(1 Suppl): 61–8.
53. Pelinka LE, et al. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma 2004;21(11):1553–61.
54. Bazarian JJ, et al. Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury. Brain Injury 2006;20(7):759–65.
55. Johnsson P, et al. Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg 2000;69(3):750–4.
56. Ergun R, et al. Prognostic value of serum neuron-specific enolase levels after head injury. Neurol Res 1998;20(5):418–20.
57. Nylen K, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci 2006;240(1–2):85–91.
58. Xydakis MS, et al. Tympanic-membrane perforation as a marker of concussive brain injury in Iraq. New Engl J Med 2007;357(8):830–1.
59. Alexander MP, et al. Impaired concentration due to frontal lobe damage from two distinct lesion sites. Neurology 2005;65(4):572–9.
60. Lee, H, et al. Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. J Neurotrauma 2008;25(9):1049–56.
61. Hughes DG, et al. Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology 2004;46(7):550–8.
62. Condon, B, et al. Early 1H magnetic resonance spectroscopy of acute head injury: four cases. J Neurotrauma 1998;15(8):563–71.
63. Garnett MR, et al. Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. Brain 2000;123(Pt 10):2046–54.
64. Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research–past, present, and future. Biol Psychiatry 2006;60(4):376–82.
65. Niogi SN, et al. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR 2008;29(5):967–73.
66. Basser PJ, Pierpaoli C Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson Ser B 1996;111(3):209–19.
67. Benzinger TL, et al. Blast-related brain injury: imaging for clinical and research applications: report of the 2008 St. Louis workshop. J Neurotrauma 2009;26(12):2127–44.
68. Lewine JD, et al. Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. AJNR 1999;20(5):857–66.
69. Huang MX, et al. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma 2009;26(8):1213–26.
70. Gaetz M, Bernstein DM. The current status of electrophysiologic procedures for the assessment of mild traumatic brain injury. J Head Trauma Rehab 2001;16(4):386–405.
71. MacDonald CL, et al. Detection of blast-related traumatic brain injury in U.S. military personnel. New Engl J Med 2011;364(22):2091–100.
41<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
Section 1: Traumatic Brain Injury
72. Gawande A. Casualties of war–military care for the wounded from Iraq and Afghanistan. New Engl J Med, 2004;351(24):2471–5.
73. Nyein MK, et al. In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury. Proc Natl Acad Sci USA 2010;107(48):20703–8.
74. Moss WC, King MJ, Blackman EG. Skull flexure from blast waves: a mechanism for brain injury with implications for helmet design. Phys Rev Lett 2009;103(10):108702.
75. Moore DF, et al. Computational biology - modeling of primary blast effects on the central nervous system. Neuroimage 2009;47(Suppl 2):T10–20.
42<i>Traumatic Brain and Spinal Cord Injury : Challenges and Developments</i>, edited by Cristina Morganti-Kossmann, et al., Cambridge University Press, 2012. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=977156. Created from apus on 2019-08-05 13:08:36.
C op
yr ig
ht ©
2 01
2. C
am br
id ge
U ni
ve rs
ity P
re ss
. A ll
rig ht
s re
se rv
ed .
