BACKGROUND:Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and health care costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. METHODS:A preliminary literature search informed a need for updated guidelines. Methodologists experienced in TBI guidelines supported 2 co-chairs, a diverse steering committee and three expert working groups. Over half of our panelists were active service military or military veterans and they addressed twenty-six Key Questions (KQs). We searched Ovid MEDLINE®, EMBASE, and Cochrane CENTRAL from inception to August 31, 2022, reference lists, and clinical trial registries. Penetrating, perforating and tangential penetrating brain injuries were included. Predefined criteria were used to identify studies; pre-specified methods were used to assess study quality and strength of evidence for key outcomes. Effects were analyzed qualitatively and quantitatively where appropriate. RESULTS:125 studies provided evidence and another 80 studies provided contextual data for these guidelines. In general there was a paucity of literature and most of the identified evidence was judged to be high risk of bias due to study design. We did not identify any studies meeting inclusion criteria for 12 KQs. The highest quality evidence, rated moderate in strength, was identified for four KQs that covered: cerebral angiography vs computed tomography angiography, the relationship between bihemispheric injury in adult pTBI and mortality, the ability of the Surviving Penetrating Injury to the Brain (SPIN) score to predict mortality, and the relationship between infection and cerebrospinal fluid fistula. Evidence for most KQs came from case series. CONCLUSIONS:The development of up-to-date evidence and consensus based clinical care guidelines and algorithms for pTBI provide guidance to care providers in the prehospital and emergency medicine, surgical and intensive care settings. Few moderately strong conclusions on the benefit of specific management strategies for penetrating brain injury could be made. Detailed reporting of patient outcomes in future studies could advance the field by providing greater evidence for specific treatments by patient population, mechanism of injury, severity of injury, and specific interventions employed.

The clinical development of implantable neural devices raises complex ethical questions about post-trial responsibilities to participants. Continued support for participants who continue to use investigational implantable neural devices requires ongoing specialist care, technical expertise, access to tertiary clinical infrastructure, and substantial financial resources to pay for the device and related procedures. However, continued access may not be possible if the trial shows no benefit, if financial barriers limit commercial viability, or if safety concerns lead to suspension or early termination. Specific ethical guidance on post-trial responsibility is urgently needed. To address this challenge within the Australian innovation context, we conducted a modified Delphi study with a multidisciplinary panel of 24 experts, including representatives from industry, bioethics, law, neurosurgery, clinical psychology/neuropsychology, clinical research, neural engineering, regulation and governance, and lived experience advocacy. The process involved two workshops and a survey, guided by established RAND/UCLA methods with context-specific modifications. Drawing on prior empirical research and regulatory review, the panel developed 11 consensus recommendations for responsible post-trial practices. All recommendations achieved high levels of agreement and were rated as highly important for addressing ethical risks in the Australian environment. These are the first jurisdiction-specific recommendations of their kind, and we anticipate they will substantially enhance ethical and practical standards for post-trial responsibility in implantable neural device research in Australia and internationally.

Importance The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. Objective To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS. Design, Setting, and Participants Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens. Interventions Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing. Main Outcomes and MeasuresThe primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; <1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164). Results Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. Conclusions and Relevance In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. Trial RegistrationClinicalTrials.gov Identifier: NCT04297683

INTRODUCTION AND IMPORTANCE:Bolt gun injuries to the head are rare and are usually in the context of suicide. Bolt guns are used in the meat processing industry to induce unconsciousness prior to slaughter. A bolt penetrates 7-10 cm through the skull into the brain and then is retracted by a spring. Mortality has been reported to be up to 80-90 %, with survivors left with severe neurological and functional deficits. CASE PRESENTATION:A 24-year-old man presented with a self-inflicted bolt gun injury to the central forehead. He presented confused and agitated to a rural emergency department and was subsequently intubated and transferred to a tertiary trauma centre. CT demonstrated a midline frontal bony defect with an underlying 8.5 cm wound tract into both frontal lobes. There was associated intracranial haemorrhage and impacted skin and bone fragments within the wound tract. CTA/V showed an injury to the superior sagittal sinus but intact arterial vessels. He underwent a bifrontal craniectomy, débridement and evacuation of haematoma with ICP monitor placement. The patient demonstrated a remarkable recovery at 3 months with only mild cognitive impairment. CLINICAL DISCUSSION:CT imaging including angiography assesses extent of parenchymal and vascular injury. Decompression of the brain and careful debridement off the brain reduced the risk of infection but prevented iatrogenic injury. Prophylactic treatment with broad-spectrum antibiotics prevented intracranial infection. CONCLUSION:This case report highlights multiple lessons which contributed to successful management of a bolt gun injury to the head: preoperative CT angiography, craniectomy if indicated, cautious debridement and prophylactic antibiotics.

To evaluate the potential for missed diagnoses of Lambert-Eaton myasthenic syndrome (LEMS) and autonomic dysfunction among patients with myasthenia gravis (MG) in the United States (US).

Brain-computer interfaces (BCIs) are devices that connect the human brain to an effector via a computer and electrode interface. BCIs may also transmit sensory data to the brain. We describe progress with the many types of surgically implanted BCIs, in which electrodes contact or penetrate the cerebral cortex. BCIs developed for restoration of movement in paralyzed limbs or control a robotic arm; restoration of somatic sensation, speech, vision, memory, hearing, and olfaction are also presented. Most devices remain experimental. Commercialization is costly, incurs financial risk, and is time consuming. There are many ethical principles that should be considered by neurosurgeons and by all those responsible for the care of people with serious neurological disability. These considerations are also paramount when the technology is used in for the purpose of enhancement of normal function and where commercial gain is a factor. A new regulatory and legislative framework is urgently required. The evolution of BCIs is occurring rapidly with advances in computer science, artificial intelligence, electronic engineering including wireless transmission, and materials science. The era of the brain-"cloud" interface is approaching.

BACKGROUND:The aim of this study was to test whether participation in an alcohol risk reduction program known as Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.) is effective in reducing the prevalence of risky drinking at 12 months' post-intervention in a sample of Royal Australian Navy (RAN) trainees.METHODS:A non-blinded randomized controlled trial of 952 RAN trainees comparing two forms of P.A.R.T.Y. plus RAN annual alcohol and other drug awareness training with annual alcohol and other drugs awareness training only (Control). Participants were screened at baseline and at 12-month follow-up using the Alcohol Use Disorders Identification Test (AUDIT). Participants were randomized to one of three arms: (1) in-hospital P.A.R.T.Y program, (2) on-base P.A.R.T.Y. program, or (3) control.The primary outcome measure was the percentage of participants reporting an AUDIT score of 8 or above at 12 months in each group. A secondary outcome considered was reports of alcohol-related incidents in the 12-month follow-up.RESULTS:There was no difference in the risk of reporting an AUDIT score of 8 or above in either the in-hospital (Relative Risk (RR) 0.96, 95% CI: 0.75-1.23; P = .75) or on-base (RR 1.11, 95% CI: 0.89-1.369; P = 0.35) intervention groups, compared to the control group. Compared to the on-base group, there was no difference in the risk of reporting an AUDIT score of 8 or above in the in-hospital group (RR 1.16, 95% CI: 0.90-1.48; P = .24). The rate of reporting an alcohol-related incident was not different for the in-hospital (Hazard Ratio (HR) 0.60, 95% CI: 0.27-1.33; P = .21) or on-base (HR 0.50, 95% CI: 0.21-1.16; P = .11) intervention groups when compared to the control group.CONCLUSION:Participation in either an on-base or an in-hospital P.A.R.T.Y. program did not affect the proportion of naval trainee participants screening positive for risky drinking on the AUDIT.

OBJECTIVES:To investigate beliefs and factors associated with padded headgear (HG) use in junior (<13 years) and youth (≥13 years) Australian football.DESIGN:Online survey.SETTING:Junior and youth athletes in Australia.PARTICIPANTS:Australian football players aged U8 to U18.ASSESSMENT OF VARIABLES:Survey questions regarding demographics, HG use, concussion history, beliefs about HG, and risk-taking propensity.MAIN OUTCOME MEASURES:Rates of padded HG use, and beliefs associated with HG use.RESULTS:A total of 735 players (including 190, 25.9% female) representing 206 clubs participated. Headgear was worn by 315 players (42.9%; 95% CI: 39.3-46.4). Most (59.5%) HG users wore it for games only and wore it voluntarily (59.7%), as opposed to being mandated to do so. Junior players were more likely than youth players to agree to feeling safer ( P < 0.001) and being able to play harder while wearing HG ( P < 0.001). Median responses were "disagree" on preferring to risk an injury than wear HG, and on experienced players not needing to wear HG. Beliefs did not differ between males and females. Headgear use was associated with players belonging to a club where HG was mandated for other age groups (OR 16.10; 95% CI: 7.71-33.62, P < 0.001), youth players (OR 2.79; 95% CI: 1.93-3.93, P < 0.001), and female players (OR 1.57; 95% CI: 1.07-2.30, P = 0.019).CONCLUSIONS:Club HG culture, older age and being female were prominent variables associated with voluntary HG use. Players reported believing that HG offers protection. The rate of voluntary and mandated HG use identified is at odds with current scientific evidence that does not support HG as effective concussion prevention.

Brain Computer Interface (BCI) devices are being developed to restore or improve the function of people suffering with neurological disabilities such as limb paralysis, sensory loss, blindness, deafness, movement disorders, memory loss, loss of speech and epilepsy. BCI technology is advancing rapidly but major challenges remain, such as biocompatibility, developing micro-electrodes which function effectively for many years, maintenance of device hermeticity, improved wireless functionality and the ability to simultaneously stimulate and record from a neural network of thousands or millions of neurons. Non-invasive devices are attractive but are far less capable compared with the spatial or functional resolution of implanted devices. Engineers need to collaborate with neurosurgeons to develop devices that significantly benefit the patient, are practical to implant with low and acceptable surgical risks, have a record of long-term safety, and can be safely explanted. Neurosurgeons should be involved in the preclinical (animal) testing of prototype devices and they need to understand the technical capability of the BCI and its experimental results to be able to discuss the BCI with the potential recipients and their families so that they can give informed consent. This chapter describes the neurosurgery/engineering collaboration necessary to successfully develop test and commercialize BCIs and also presents the full range of BCI applications. The ethical considerations concerning the development and application of BCIs will also be presented.

BACKGROUND:Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE:To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS:We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS:Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION:Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Best practice guidelines have advanced severe traumatic brain injury (TBI) care, however, little currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, acceptability of neurological outcomes as well as putative means of improving decisions which may limit care. 97.6% of the 42 SIBICC panelists completed the survey. Responses were highly variable to most questions. Overall panelists reported infrequent use of prognostic calculators and observing variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a 'nihilism guard'. Over 50% of panelists felt that if it was certain to be enduring, a vegetative state or lower severe disability would justify a withdrawal of care decision while 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, a 64-69% chance of a poor outcome on average was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes which might prompt consideration of care withdrawal, however imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care limiting decisions. Keywords: nihilism, withdrawal of care, survey, SIBICC, brain injury, prognosis.

Evidence from recent trials evaluating efficacy of antifibrinolytic agents in the context of traumatic brain injury may lead to changes in the management of patients with traumatic brain injury. Tranexamic acid (TXA) reduces the proteolytic action of plasmin on fibrin clots, resulting in an inhibition of fibrinolysis and stabilisation of established blood clots. There has been significant interest in use of the drug as a therapeutic agent in the context of severe haemorrhage; however, considerable controversies regarding its efficacy remain. A number of trials have demonstrated a small but significant decrease in mortality following its administration, but the results have been somewhat inconsistent and may not be generalisable. The results of the CRASH-3 trial were that there was no statistical difference in the number of traumatic brain injury related deaths (18.5% with TXA and 19.8% with placebo; relative risk [RR] 0·94; 95% confidence interval [CI] 0·86-1·02). Nonetheless, there was a subgroup of patients for whom TXA appeared to provide benefit, and this was in patients with mild and moderate injury (with a Glasgow Coma Score > 8). This is potentially a very important finding that may have huge potential implications; however, we believe it does not currently provide indisputable evidence to support the administration of TXA to all patients with TBI. Further work is required to better define the subset of patients who may benefit as well as to evaluate the long-term functional benefit in order to determine which types of severe traumatic brain injury patients would derive more benefits than harms from TXA.

The advent of the COVID-19 pandemic with its extreme pressure on resources and intensive care beds has prompted many healthcare providers to consider more fully the potentially futile nature of some treatments and how resources might be better managed. This is especially relevant in the context of neurosurgery which is highly resource dependent in terms of technology, funding, and manpower and it may be difficult to balance fair, equitable and sustainable resource allocation, especially in circumstances where those healthcare resources become limited or completely exhausted. Indeed, it may be necessary to consider limiting the availability of certain neurosurgical services or perhaps reconsider the utility or otherwise of performing procedures that commit very restricted resources, such as intensive care beds, to patients who are arguably receiving limited long-term benefit. In these circumstances, the decision-making paradigm is challenging and there are several ethically disparate viewpoints that need to be reconciled. These include but are not limited to, Futility, Utilitarianism and the Rule of rescue

The wide-spread use of an initial ‘Glasgow Coma Scale (GCS) 8 or less’ to define and dichotomise ‘severe’ from ‘mild’ or ‘moderate’ traumatic brain injury (TBI) is an out-dated research heuristic that has become an epidemiological convenience transfixing clinical care. Triaging based on GCS can delay the care of patients who have rapidly evolving injuries. Sole reliance on the initial GCS can therefore provide a false sense of security to caregivers and fail to provide timely care for patients presenting with GCS greater than 8. Nearly 50 years after the development of the GCS – and the resultant misplaced clinical and statistical definitions – TBI remains a heterogeneous entity, in which ‘best practice’ and ‘prognoses’ are poorly stratified by GCS alone. There is an urgent need for a paradigm shift towards more effective initial assessment of TBI.

BackgroundGiven the neurotrauma that soldiers might face during wars, a byproduct of such devastating neurosurgical conditions can be novel data, which can act as a catalyst for potentially paradigm-shifting research. We aimed to identify the impact of major U.S. military campaigns on military neurosurgery literature across defined time periods.MethodsA comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies from 1915 to 2021 relevant to military neurosurgery. A discrete set of validated informetric metadata parameters were extracted and analyzed using productivity analysis, citation analysis, keyword analysis, text mining, content analysis, and collaboration network mapping.ResultsOur search yielded 2216 documents. Annual scientific production since 1915 grew at a compounded rate of 6.1% per year, with the most significant increases during U.S. military campaigns (coefficient = 42.9, P < 0.001) and following the introduction of the Department of Defense Trauma Registry in 2007 (coefficient = 114.5; P < 0.001). Each war had a direct influence on military neurosurgery literature growth (P < 0.05), with the most prominent following the Afghanistan war. The journals with the most publications on military neurosurgery were Military Medicine (n = 168) and Journal of Head Trauma. The topmost cited author was Hoge et al. (N = 2083), while the topmost cited country was the United States (N = 1098).ConclusionsSince World War II, the military has contributed significant historical developments to neurosurgery, the most prominent being after the Iraq and Afghanistan wars and the introduction of the Department of Defense Trauma Registry.

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.

Over the course of history, human conflict has been responsible for immeasurable loss of life.Care for the wounded evolved desultorily during this time, and though many believe that war has accelerated medical and surgical progress to the benefit of both military and civilian lives, many believe that the benefit may not be as significant as one might hope or believe.One cannot deny, however, that war has influenced medicine in many ways.From the evolution of the ambulance, triage medicine, and ventilated, open-spaced "hospitals," to the development of antibiotics, mobile x-ray units, and concepts in wound care, military medicine was borne from the dire circumstances of the wounded and the desire and need to heal and maintain a healthy fighting force.More recent military medical advancements in trauma systems, prehospital resuscitation, hemostatic agents, damage control surgery, burn care, endovascular stents, and many others have influenced civilian practice.The field of neurological surgery experienced a similar revolution during years of war.This issue of Neurosurgical Focus highlights original contributions to the progress of neurosurgery forged from war.The reader will learn about the legacy and contributions to trauma surgery and neurosurgery during the Renaissance by Paré and Dalla Croce.Brief biographical