Rocco A. Armonda

Throughout my career I have always moved to the direction of "gun-fire" in an effort to make a difference. As a military medical officer it was plainly expected, you "shadow" those in harm's way - you are there, ready and able when they need you. This was best exemplified 20 year ago operating out of a tent in the Iraqi desert because it was where we were needed. Today, I feel that same obligation in a major metropolitan tertiary care medical center in our nation's capital. However, I didn't expect to see the current level of penetrating trauma that we have seen in a combat zone. Unfortunately, in many ways the war has returned home. In this way, the number of pTBI victims and patterns of complex neurovascular injuries continues to challenge the limits of our resources and technology regardless of our geography.

Overseas recently this was evident to me assisting neurosurgeons in Dnipro, Ukraine. A large scale European land war has not been seen for over 80 years. The number of casualties is easily 5-10x the volume we saw in 20 years of Middle Eastern wars. At one hospital over 18,000 combat casualties have been treated. This includes civilians caught in the missile and artillery attacks on apartments, train stations, churches, schools, hospital and even theaters. During this period I witnessed the application of a generation of advances made in pTBI care. Over 30% of these patients had concomitant neurovascular injuries. These injuries were being treated only hours from the frontlines in a major 1200 bed hospital - Mechnikov Medical Center - with the most advanced neurosurgical and neuroendovascular techniques available in the world. Definitive decompression, debridement and reconstruction of complex skull-base injuries were being performed. In fact, this was the exact procedure performed for the first patient I assisted in treating. A transbasal bifrontal penetrating brain injury with embedded bone and metal fragments into the interhemispheric fissure and ventricular system with an anterior cerebral artery branch psuedoaneurysm and violation of the frontal air sinuses. All of his treatment was under the direction of Professor Andrii Sirko who leads the division and has performed over 700 pTBI surgeries. His experience was built on many of our lessons learned from Iraq/Afghanistan as well as over 9 years of war in the Donbas and Crimea since 2014. His team's experience is rewriting the book on advance management of wartime penetrating neurotrauma.

As we face an epidemic of gun violence in the US there is much we can learn from our Ukrainian compatriots. Unfortunately, over the past 20 years our neighborhoods, schools, places of worship, even community parades and celebrations have become site of mass casualties from gun violence. The burden of care for these victims has unequally fallen onto these families and the providers in safety net hospitals through out major US cities. Our paradigm for saving lives and function has been transformed by this experience as neurosurgeons.

US military casualty care over the past 20 years and ongoing lessons learning from Ukraine have increased our ability to treat these devastating injuries. No longer is a nihilist approach appropriate in most penetrating brain injuries. Military medical models of multi-modal management with whole blood resuscitation, avoiding hypotension, early screening for neurovascular injuries and early neurosurgical management has been extended into the civilian arena. Principals of "damage-control" surgery have been applied to neurosurgical treatment of pTBI.

These guidelines reflect the global efforts of multiple subspecialists to provide the best framework for caring for the pTBI patient. A variety of backgrounds from both military and civilian centers throughout the world is reflected in this compendium. The meticulous review of the world's literature and application to pressing practical decision making is our foundation. The ultimate goal being to elevate, standardize and optimize recovery in the pTBI patient.

Early and timely resuscitation, followed by appropriate surgical decompression, debridement, hemostasis and prevention of secondary injury is our focus. The role for management of occult neurovascular injures has rapidly expanded with the advent of neuro-endovascular technology. Devices and techniques not previously available 20 years ago are being applied throughout the world from Ukraine to Washington, DC for penetrating neurovascular injuries. The published literature does not yet reflected the current use of these techniques which will continue to evolve as the technology does. We have tried to capture early experience from military and civilian series on the application of these techniques for our current recommendations. However, publication of current techniques and applications will not be reflected in the literature for several more years.

This rapid shift in the treatment of pTBI patients begins with a fundamental shift in our approach to the disease. No longer should all pTBI patients be seen as "expectant", in fact we emphasize the reverse - that neurosurgical intervention should be considered a first priority. Reversing the sequalae of coagulopathy, brain swelling, herniation and neurovascular injury is our primary focus. Countering the self-fulfilling prophecy of non-intervention and therapeutic nihilism is one of our greatest challenges.

Reports in the press are replete with amazing recoveries from patients who were afforded the best of pTBI management. Recoverable patients whose care was delayed or not performed are rarely reported. We are hopeful that by codifying these treatments in easy-to-use algorithms that others can be saved. The first step involves neurosurgical leadership in the surgical management of these patients. The care of such complex patients should not be abdicated nor deferred. Timely intervention will require immediate applications of essential resources from the blood bank, operating room, and neurosurgical OR/NeuroIR teams.

Much like the 'golden hour' of trauma care we have identified outcomes related to timeliness and type of neurosurgical intervention. Limitations exist in establishing level I evidence for pTBI care. This reflects the nature of these injuries, whereby a control arm is ethically unfeasible. The majority of the recommendations have come down to expert opinion based on extensive literature review mixed with decades of both military and civilian experience. Additionally, given the hostile medical-legal environment in the US it is unconscionable to universally apply broad algorithms without individualization to specific patients, imaging and clinical evaluations.

The management of specific injury patterns in pTBI have also been addressed in this work. Involvement of the skull base with concomitant air-sinus involvement and orbito-facial skeleton have been outlined. The role for staging reconstructions and preventing secondary CSF leaks, encephaloceles, and delayed infections has been addressed. Additionally, the management of retained bone and metal fragment has been addressed. These principals need to be applied to specific individual patient cases as appropriate. Our consensus reflects what we feel to be the best management principals based on the available literature and expert opinion.

A rigorous approach has been made to avoid bias associated with commercial affiliations or personal preference. We have avoided advocating for use of a particular medical device in all instances. Authors of major publications who were part of the consensus ensured that other specialists reviewed their contributions objectively and per the structure established for grading strength of evidence and recommendations.

We hope that this effort will improve care for pTBI patients and lead to further advances in the care of victims of senseless violence that has plagued our streets and our world. May the algorithms, guidelines and consensus statements in these guidelines aid the individual neurosurgeons trying to reverse the otherwise inevitable outcome of pTBI. May these guidelines provide the path forward for more lives to be saved. Ultimately it is up to us as frontline neurosurgeons as no one else is better qualified to lead by example.

David Okonkwo, Guy Rosenthal

The patient who survives a penetrating traumatic brain injury is expected to have a good functional outcome and return to independent living. The modern experience with treatment of gunshot wounds to the head, and other forms of penetrating TBI reveals that rapid surgical management, intensive medical care, and prompt management of ensuing complications allows for lives to be saved and restored. To the less experienced, these outstanding outcomes appear "unexpected"; to those in the trenches, these outcomes are anticipated and intentional and the gift of expert care.

Herein, we issue the updated Guidelines for the Management of Penetrating TBI. The Guidelines represent a monumental team effort and collaboration from experts across the globe, with representation from civilian and military medicine.

Too often, the patient with a penetrating TBI is deemed "non-survivable". This determination is far too often a reflection of bias in the clinician and erroneous for the patient. The National Academy of Medicine issued a report in 2022 highlighting that the quality of care for TBI is driven in large measure by the zip code of the patient's injury. For victims of gunshot wounds to the head, the best proxy for "quality of care" is the degree of nihilism exhibited by clinicians at the local trauma center. On the contrary, early, aggressive neurosurgical, endovascular and critical care underscores the ethos of the centers with the best outcomes. This is best illustrated in the military conflicts of the last quarter century, with the highest survival rates and lowest disability rates of any cohort of gunshot wounds to the head in history. Great outcomes are achievable. These Guidelines, and the NASEM Forum on Traumatic Brain Injury, are calls to action for every trauma center in America to engage in self-reflection and seek self-improvement. We can all be inspired by our military medicine colleagues to do more and do better for every patient.

For survivors of pTBI, the injury morphs into a chronic disease. Seizures, hydrocephalus, delayed infections, soft tissue dilemmas, neuropsychological manifestations are a partial list of things that require ongoing care and attention. We need clinicians and TBI care pathways committed to seeing these patients through more than just the initial hospitalization.

The adage "an ounce of prevention is worth a pound of cure" is perhaps more relevant to gunshot wounds than many other medical conditions. Prevention strategies are beyond the scope of these Guidelines; yet, the authors covet a time where these guidelines are moot as there are no gunshot victims. Nevertheless, it is of vital importance to raise expectations in centers caring for penetrating TBI victims and endow clinicians with the evidence and tools needed to maximize outcomes.

There is no greater reward for the clinician than to see a patient emerge from crisis and again experience the joy of life's big and little moments. These victories are achieved every day following pTBI and the modern military experience proves this. Victories for patients and families can be achieved more frequently and in more hospitals around the globe if trauma centers embrace the challenge of difficult cases, eliminate nihilism, and commit to aggressive care.

Penetrating Brain Injury: New Guidelines for a New Paradigm

Christos Lazaridis MD, EDIC, Fernando D. Goldenberg MD, FNCS, Ali Mansour MD, MScBMI

Section of Neurocritical Care, Departments of Neurology and Neurosurgery, The University of Chicago, Chicago, IL, USA

Almost half of traumatic brain injury (TBI)-related deaths from 2016 to 2018 in the United States (US) were due to firearm-inflicted penetrating traumatic brain injury (pTBI) secondary to suicides and homicides. Young males in metropolitan areas, and non-Hispanic Blacks are disproportionally affected, with increasing rates among women in relation to domestic violence. In 2020, firearm-related injuries surpassed motor vehicle accidents as the leading cause of death in the ages 1-19 in the US. Penetrating brain injury has been reported to carry 60% to 90% all-comer mortality and accounts for approximately 20,000 civilian deaths per year in the US. For pediatric (mean age 15) and adult (mean age 36) patients who arrive to a level I or II trauma center with pTBI, mortality ranges 45-55%. Of note, these rates compare unfavorably with the observed mortality of 20-30% in contemporary cohorts of critically ill blunt TBI patients. Concurrently, a knowledge hiatus exists due to lack of dedicated investigation in combination with a systematic exclusion of pTBI from recent large prospective TBI research efforts. Admittedly, pTBI is relatively rare as it accounts for less than 2% of all TBI incidents. The low overall incidence in combination with projections of universally poor outcomes may have hampered efforts to develop new knowledge in the field. However, pTBI burden is unequally shared as it heavily concentrates in a few large cities, and specific communities and trauma centers within these cities. Firearm injuries have been shown to be a critical driver of health disparities in the US.

A recent cross-sectional study of almost 130,000 subjects found that individuals from zip codes with the most violence in Chicago and Philadelphia had a significantly higher risk of firearm-related death than US military personnel who served during the wars in Afghanistan and Iraq. Risks were overwhelmingly borne by young adult males from minoritized racial and ethnic groups. This reflects our experience at the University of Chicago Medical Center (UCMC), where we have been treating disproportionately high rates of pTBI. The UCMC Level 1 Adult Trauma Center opened in May 2018. In a period of about 5 years, we have cared for over 300 adult pTBI patients, half of them with isolated brain injury and an overall 50% mortality. For patients requiring intensive care for severe brain injury, most of our cohort comprised pTBI vs. blunt TBI. With this background in mind, we excitedly welcome the publication of the updated pTBI clinical practice guidelines, an effort by the Brain Trauma Foundation, in collaboration with an expert group and funding from the American Department of Defense. The update comes to replace the original version first published in 2001, and it reflects a paradigm shift towards more aggressive and targeted neurosurgical and critical care approaches. This is largely motivated by emerging evidence from military pTBI cohorts and comparative effectiveness research (CER) employing the National Trauma Data Bank (NTDB), jointly suggesting that increasing targeted therapeutic intensity may lessen pTBI mortality and improve outcomes. Another important feature is the increased recognition of pTBI as a complex cerebrovascular disease; this, in combination with the constant evolution of endovascular interventional techniques, generates anew attention to the study and management of these challenging injuries. We briefly expand on these changes below.

Early decompressive craniectomy (DC) has been a favored damage-control approach in the setting of combat-related pTBI, with one study showing mortality benefit if performed within 6 hours of injury. To investigate the role of early neurosurgical intervention in civilians (first 24 hours), we recently explored the Trauma Quality Improvement Program (TQIP) of the NTDB from 2017 to 2019. Following a CER approach, we compared propensity matched cohorts and showed that in patients 16-60 years of age, with predominantly isolated, moderate, or severe firearm-related PBI, management that includes early neurosurgery is associated with decreased mortality. This combined civilian and military data, point to an approach of early aggressive neurosurgical care as a means to decrease mortality in selected patients with firearm-induced brain injury. Concurrently, these results should motivate future prospective CER and randomized controlled trials to further define the role of acute resuscitative neurosurgery in the management of pTBI. A similar methodology was pursued to examine the role of clinical management that includes intracranial pressure (ICP) monitoring vs. no monitoring in matched pTBI cohorts. The inclusion of ICP monitoring was associated with higher chances of survival in patients with severe pTBI. These two studies taken together recommend against a nihilistic approach; aggressive resuscitation including neurocritical care and early neurosurgical intervention may be associated with survival. Notably, there are currently no published civilian pTBI treatment algorithms, and it is likely that large variability in practices exist among different centers. The above studies and the updated guidelines could serve as starting points to standardize pTBI management strategies. These findings require prospective validation in conjunction with precision medicine methodologies to optimize patient selection. Such approaches can contribute to further updating and transforming guidelines into a living repository of continuously updated evidence.

Penetrating brain injury may have important phenotypic differences from blunt TBI, and this becomes particularly evident in considering associated cerebrovascular injury (CVI). Recent single center studies where early vascular imaging is employed, reveal a prevalence of up to 50-60% of either arterial, venous, or combined insults. Reported injuries include dissections, pseudoaneurysms, large vessel occlusions, transections, high flow carotid-cavernous fistulas, venous sinuses ruptures and occlusions. Patient features that closely associate with CVI include projectiles penetrating the frontobasal skull region, trajectories crossing multiple lobes, bihemispheric injury, and presence of subarachnoid and intraventricular hemorrhage. Patients with CVI experience higher mortality and poorer functional outcomes. Screening all patients with early computed tomography arterio- and venography (CTA/CTV) is strongly recommended, followed by conventional cerebral angiography as indicated (particularly when pseudoaneurysms are identified), and prompt vascular imaging follow up.

We expect that the new PBI guidelines will bring more attention to the management and study of civilian and military pTBI. Furthermore, as it has happened in blunt TBI, adherence to guidelines holds potential to improve clinical outcomes and refine future research endeavors. For this to materialize adherence needs to be monitored in conjunction with auditing of short and long-term outcomes. The generation of prospective high-quality evidence should remain a priority. The TBI research community strongly supports CER in addition to clinical trials as a way of evidence generation. To be able to generate impactful evidence, and to further endotype the disease, it is imperative to consider the formation of a consortium of high-volume pTBI centers (including civilian and military cohorts), and to standardize data collection via common data elements (CDEs). We recently held the 1st Annual Chicago Neurotrauma Symposium: Penetrating Brain Injury: Toward a New Paradigm (Chicago, IL, September 29-30, 2023). This conference brought together experts from civilian and military medicine, basic scientists, policy, and funding stakeholders. Establishing a consortium that can arise by performing high quality prospective clinical and epidemiological data collection was uniformly endorsed as a priority for the field of pTBI.

The overarching aims of such a collaboration will be to characterize the disease itself and the care that is provided across centers. Eventually, this should provide the ability to develop performance indicators for quality assurance and quality improvement in pTBI care. Concurrent goals include building the infrastructure for repositories that will serve developing and validating biofluid and radiographic markers to further phenotype patients and understand their clinical trajectories. In terms of clinical approaches, CER methodologies are ideal in exploiting natural inter-center variabilities in structure, process, and outcomes to compare interventions. Specifically, for pTBI, ballistics and structural context as in civilian vs. military will be important to consider and adjust for. Concurrently, we recognize clear challenges related to the overall low incidence of pTBI in combination with large inter-regional discrepancies. Identification of eligible high-volume centers will have to anticipate that some of these may have no resources or experience with prospective multimodal data capture. A pragmatic challenge is also the imperative need for dedicated funding; as the condition is of significant epidemiologic concern for both civilians and military personnel, seeking support should meet the mission desiderata of both the National Institutes of Health and the Department of Defense. Networking with international collaborators will also be important, recognizing again significant structural differences in injury causation and management.

We reviewed above the motivation for updates in the clinical guidelines referring to acute neurosurgical management, ICP monitoring, and CVI, as well as sketched an outline for a pTBI consortium formation. In closing, we mention several more salient aspects of acute care that are of pressing need to refine and harness evidence for, such as optimal resuscitation strategies, initial blood pressure and blood product goals, the role of coagulopathy, and combined cranial-extracranial surgery. Development of clinical triage algorithms would be greatly enhanced by understanding imaging features and predictors of intervention responsiveness. Finally, it should not be missed the scarcity of long-term neurologic and psychosocial outcome data in pTBI survivors. Strategies for successful long-term follow up are as essential as identifying social determinants of disease and outcomes. Our current approach to pTBI remains lacking; the new guidelines mark a new start and paradigm.