Operations Desert Shield and Desert Storm: neurosurgical experience and transformative legacy for operational medicine.

Operation Desert Storm (ODS) was an astounding success for combat arms and logistical units of the US Military. In contrast, Department of Defense (DOD) medical units struggled to keep pace with combat operations and were fortunate that casualty estimates for a Cold War-era battle failed to materialize. The medical support plan included a large contingent of active-duty and reserve neurosurgeons in anticipation of care requirements for more than 500,000 deploying service members engaged in a large-scale combat operation. Here, the authors review the clinical experience and operational challenges encountered by neurosurgeons deployed in support of this conflict and discuss legacies of ODS for both surgeons and the military medical system.

Operation "NeuroTeam": rendering the absolute best care for the most deserving patients under the most difficult conditions.

The tenets of neurosurgery worldwide, whether in the civilian or military sector, espouse vigilance, the ability to adapt, extreme ownership, and, of course, an innate drive for developing a unique set of technical skills. At a time in history when the complexity of battlefield neurotrauma climaxed coupled with a chronic shortage of military neurosurgeons, modernized solutions were mandated in order to deliver world-class neurological care to our servicemen and servicewomen. Complex blast injuries, as caused by an increased incidence of improvised explosive devices, yielded widespread systemic inflammatory responses with multiorgan damage. In response to these challenges, the "NeuroTeam," originally a unit of two neurosurgeons as deployed during Operation Desert Storm, was redesigned to instead pair a neurosurgeon with a neurointensivist and launched itself during two specialized missions in Operations Iraqi Freedom and Enduring Freedom. Representing a hybridized version of present-day neurocritical care teams, the purpose of this unit was to optimize neurosurgical care by focusing on interdisciplinary collaboration in an Echelon III combat support hospital. The NeuroTeam provided unique workflow capabilities never seen collectively on the battlefield: downrange neurosurgical capability by a board-certified neurological surgeon within 60 minutes from the point of injury paired with a neurocritical care-trained intensivist. This also set the stage for intraoperative telemedicine infrastructure for neurosurgery and optimized the ability to evaluate, triage, and stabilize patients prior to medical evacuation. This novel military partnership ultimately allowed the neurosurgeon to focus on the tenets of the craft and thereby the dynamic needs of the patient first and foremost. Since the success of these missions, the NeuroTeam has evolved into a detachable unit, the "Head and Neck Team," comprising neurosurgeons, otolaryngologists, and ophthalmologists, supported by a postinjury hospital unit, which includes an embedded neurocritical care physician. The creation and evolution of the NeuroTeam, necessitated by a shortage of military neurosurgeons and the dangerous shift in military wartime tactics, best exemplifies multidisciplinary collaboration and military medicine agility. As neurocritical care continues to evolve into a highly complex, distinct specialty, the lessons learned by the NeuroTeam ultimately serve as a reminder for civilian and military physicians alike. Despite the conditions and despite one's professional ego, patients with highly complex morbid neurological disease deserve expert, multidisciplinary management for survival.

Rationale and Methods for Updated Guidelines for the Management of Penetrating Traumatic Brain Injury.

Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings.

Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.

The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6x10-4), IFN-γ (FDR = 1.3x10-3), IL-13 (FDR = 1.6x10-3), CCL11 (FDR = 2.1x10-3), IL-12p70 (FDR = 2.2x10-3), IL-8 (FDR = 2.2x10-3), CXCL10 (FDR = 3.1x10-3), CCL4 (FDR = 5.7x10-3), IL-12p40 (FDR = 7.1x10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2x10-7 and P = 2x10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.

Association of a Functional Polymorphism in the CHRFAM7A Gene with Inflammatory Response Mediators and Neuropathic Pain after Spinal Cord Injury.

The alpha 7 nicotinic acetylcholine receptor, α7 nAChR, plays a central role in regulating inflammatory responses. Previous studies showed that pharmacological inhibitors of α7nAChR have a pro-inflammatory effect, increasing the circulating levels of cytokines such as tumor necrosis factor alpha (TNFα). This study focused on how genetic polymorphisms of the partially duplicated α7nAChR gene (CHRFAM7A), which is highly expressed in peripheral blood cells, contribute to functional outcome after spinal cord injury (SCI). In a cohort of 27 SCI patients and 25 emergency room consented controls (% F/M: 15/85, 24/76; mean ± SE age: 35 ± 1.38 and 35 ± 2.0 respectively), a panel of circulating cytokines, noradrenergic metabolite (normetanephrine [NMN]) levels, and clinical data were available within the first 7 days post-injury (DPI) up to 90 DPI, and were investigated in the acute/subacute (DPI 1-21) and intermediate (DPI 22-90) temporal periods. Cytokine and NMN plasma levels on different DPI were analyzed as a function of CHRFAM7A genotype. TNFα levels, as a representative of some elevated inflammatory mediators, were nearly threefold higher in individuals carrying the del-2bp variant of the CHRFAM7A gene compared with that in the no-deletion genotype (p = 0.001 analysis of variance [ANOVA]) 3 weeks DPI, and twofold higher than genotype-matched acute/subacute non-SCI injury controls within 7 days DPI. In contrast, NMN levels were initially unchanged, although after 3 weeks, NMN levels were significantly decreased in SCI individuals carrying the del-2bp variant compared with non-carriers (p = 0.011 ANOVA). Numerical pain scores over this same period post-injury were significantly elevated in SCI patients carrying the del-2bp variant relative to non-carriers (p = 0.001 ANOVA). Taken together, these data reveal that pro-inflammatory responses associated with CHRFAM7A gene variation may also be associated with differences in pain experience in patients following SCI, at least during the intermediate phase.

Neurosurgical management in traumatic brain injury.

Severe traumatic brain injury (TBI) is one of the most complex and diverse pathologic medical conditions. Each year, approximately 100,000 patients require neurosurgical evacuation of an intracranial hematoma in the United States. It is essential, early in the clinical course, to distinguish those patients with severe TBI who require operative intervention from those who can be managed with only conservative measures. The surgical technique employed is determined primarily by the specific underlying pathology in conjunction with the patient's other comorbidities.

Acute management of military-related injury.

Since the dawn of armed conflict head trauma has remained one of the most challenging afflictions for surgeons and medical personnel to treat. Interventions for head trauma from antiquity through the American Civil War were met with dismal outcomes. In the 20th century, despite greater lethality of weapons, progressive advances in management led to improved outcomes for head injured patients. A triage system consisting of appropriate levels of care from the front lines, through combat support hospitals to reconstructive and rehabilitative hospitals, has also contributed to the improved outcomes of head injured patients. This chapter examines the progressive improvement in management strategies during major conflicts, the mechanisms causing head trauma during conflict, and the current medical and surgical therapies recommended in the care of head-injured patients during armed conflict.

Establishment of the Military Neurosurgeons Committee within the World Federation of Neurosurgical Societies.

In 2009, during the World Congress of Neurological Surgery in Boston, Massachusetts, the World Federation of Neurosurgical Societies (WFNS) Executive Committee decided to establish a Military Neurosurgeons Committee. A separate scientific session on military neurosurgery was held at the next WFNS Interim Meeting in September 2011 in Brazil. A further separate session on military neurosurgery will take place at the next WFNS Meeting in Seoul, South Korea.

Traumatic brain injury in modern war.

PURPOSE OF REVIEW: To review the emerging literature on traumatic brain injury (TBI) caused by explosive blast. RECENT FINDINGS: Efforts are underway to understand how explosive blast injures brain, what is the clinical presentation and how best to manage it. A major way blast injures brain is from detonation pressure waves coupling to a victim's head leading to brain deformation. The effect of other explosion-related elements is unknown. Because scientific insights take time to develop but injuries are occurring now, the military adopts existing civilian standard of care practices developed for similar diseases, such as the Guidelines for the Management of Severe Traumatic Brain Injury developed mainly for closed head TBI. When these do not exist, the military creates them, such as the Veterans Administration and Department of Defense Clinical Practice Guidelines for Concussion/Mild TBI. Another treatment advance is the creation of the first large system-wide approach to diagnosis and clinical management of TBI, which begins at the site of injury and extends through both the military and the Veterans' Administration medical care systems. SUMMARY: Explosive blast TBI is being addressed at all levels - basic research through clinical care. New clinical practice guidelines are being used in a standardized system-wide approach.

Surgical innovations arising from the Iraq and Afghanistan wars.

The delivery of combat casualty care poses numerous challenges including austere conditions, limited supplies and medical personnel, and multiple simultaneous patients. However, the exigent circumstances of the battlefield compel the development of research and the advancement of adaptive, practical medical technologies to support and sustain military health. In Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), modern changes in medical management, coupled with improved protective gear and evacuation capabilities, have facilitated the highest survival rate in combat history.

Explosive blast neurotrauma.

Explosive blast traumatic brain injury (TBI) is one of the more serious wounds suffered by United States service members injured in the current conflicts in Iraq and Afghanistan. Some military medical treatments for blast TBI that have been introduced successfully in the war theater include decompressive craniectomy, cerebral angiography, transcranial Doppler, hypertonic resuscitation fluids, among others. Stateside neurosurgery, neuro-critical care, and rehabilitation for these patients have similarly progressed. With experience, military physicians have been able to clinically describe blast TBI across the entire severity spectrum. One important clinical finding is that a significant number of severe blast TBI victims develop pseudoaneurysms and vasospasm, which can lead to delayed decompensation. Another is that mild blast TBI shares clinical features with post-traumatic stress disorder (PTSD). Observations suggest that the mechanism by which explosive blast injures the central nervous system may be more complex than initially assumed. Rigorous study at the basic science and clinical levels, including detailed biomechanical analysis, is needed to improve understanding of this disease. A comprehensive epidemiological study is also warranted to determine the prevalence of this disease and the factors that contribute most to the risk of developing it. Sadly, this military-specific disease has significant potential to become a civilian one as well.

An introductory characterization of a combat-casualty-care relevant swine model of closed head injury resulting from exposure to explosive blast.

Explosive blast has been extensively used as a tactical weapon in Operation Iraqi Freedom (OIF) and more recently in Operation Enduring Freedom(OEF). The polytraumatic nature of blast injuries is evidence of their effectiveness,and brain injury is a frequent and debilitating form of this trauma. In-theater clinical observations of brain-injured casualties have shown that edema, intracranial hemorrhage, and vasospasm are the most salient pathophysiological characteristics of blast injury to the brain. Unfortunately, little is known about exactly how an explosion produces these sequelae as well as others that are less well documented. Consequently, the principal objective of the current report is to present a swine model of explosive blast injury to the brain. This model was developed during Phase I of the DARPA (Defense Advanced Research Projects Agency) PREVENT (Preventing Violent Explosive Neurotrauma) blast research program. A second objective is to present data that illustrate the capabilities of this model to study the proximal biomechanical causes and the resulting pathophysiological, biochemical,neuropathological, and neurological consequences of explosive blast injury to the swine brain. In the concluding section of this article, the advantages and limitations of the model are considered, explosive and air-overpressure models are compared, and the physical properties of an explosion are identified that potentially contributed to the in-theater closed head injuries resulting from explosions of improvised explosive devices (IEDs).

From the battlefront: peripheral nerve surgery in modern day warfare.

Warfare historically causes a large number of peripheral nerve injuries. During the current global war on terror, an increased use of advanced regional anesthesia techniques appears to have significantly reduced pain syndromes that have been previously reported with missile-induced nerve injuries. Additionally, a new program has been established to develop advanced prosthetic devises that can interface with neural tissue to obtain direct neural control. As this technology matures, the functional restoration gained from these new generation prosthetic devices may exceed that which can be obtained by standard nerve repair techniques.

Effect of penetrating brain injury on aquaporin-4 expression using a rat model.

Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, including penetrating brain injury (PBI). Aquaporin-4 (AQP4) water channel is predominantly expressed by astrocytes and plays an important role in regulating water balance in the normal and injured brain. Using a rat model of PBI, we show that AQP4 immunoreactivity was substantially increased in the peri-injury area at both 24 and 72 h after PBI. The increase in AQP4 expression was paralleled by increased GFAP expression. The two proteins were co-expressed by peri-vascular astrocytes, whereas reactive astroglia identified by their stellar morphology did not express AQP4 at either time points after injury. Western analysis confirmed the increase in AQP4 immunoreactivity observed in the injured tissue. The apparent increase in AQP4 immunoreactivity was likely due to de novo AQP4 protein synthesis, as most of the increased AQP4 immunoreactivity was found in the soluble (cytosolic) fraction. Our results demonstrate dynamic spatial and temporal changes in AQP4 expression that contribute to the molecular pathophysiology of PBI.