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.

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.

Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Head injury and 25-year risk of dementia.

INTRODUCTION: Head injury is associated with significant morbidity and mortality. Long-term associations of head injury with dementia in community-based populations are less clear. METHODS: Prospective cohort study of 14,376 participants (mean age 54 years at baseline, 56% female, 27% Black, 24% with head injury) enrolled in the Atherosclerosis Risk in Communities (ARIC) Study. Head injury was defined using self-report and International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. Dementia was defined using cognitive assessments, informant interviews, and ICD-9/10 and death certificate codes. RESULTS: Head injury was associated with risk of dementia (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.3-1.57), with evidence of dose-response (1 head injury: HR = 1.25, 95% CI = 1.13-1.39, 2+ head injuries: HR = 2.14, 95% CI = 1.86-2.46). There was evidence for stronger associations among female participants (HR = 1.69, 95% CI = 1.51-1.90) versus male participants (HR = 1.15, 95% CI = 1.00-1.32), P-for-interaction < .001, and among White participants (HR = 1.55, 95% CI = 1.40-1.72) versus Black participants (HR = 1.22, 95% CI = 1.02-1.45), P-for-interaction = .008. DISCUSSION: In this community-based cohort with 25-year follow-up, head injury was associated with increased dementia risk in a dose-dependent manner, with stronger associations among female participants and White participants.

The Curing Coma Campaign: Framing Initial Scientific Challenges-Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting.

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.

Aerial drones for blood delivery.

Aerial drone technology is now in use to improve medical care, especially blood delivery. The use of aerial drones is broader than just this and includes aerial photography, express shipping and delivery, disaster management, search and rescue operations, crop monitoring, weather tracking, law enforcement, and structural assessment. This wide use promises to accelerate and, ideally, reduce the cost of technological advances of drones. By doing so, drone use offers the opportunity of improving health care, particularly in remote and/or underserved environments by decreasing lab testing turnaround times, enabling just-in-time lifesaving medical supply/device delivery, and reducing costs of routine prescription care in rural areas.

Management of moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.

Practice Guideline Update Recommendations Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research.

OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition on minimally conscious state (MCS) and provide care recommendations for patients with prolonged disorders of consciousness (DoC). METHODS: Recommendations were based on systematic review evidence, related evidence, care principles, and inferences using a modified Delphi consensus process according to the AAN 2011 process manual, as amended. RECOMMENDATIONS: Clinicians should identify and treat confounding conditions, optimize arousal, and perform serial standardized assessments to improve diagnostic accuracy in adults and children with prolonged DoC (Level B). Clinicians should counsel families that for adults, MCS (vs vegetative state [VS]/ unresponsive wakefulness syndrome [UWS]) and traumatic (vs nontraumatic) etiology are associated with more favorable outcomes (Level B). When prognosis is poor, long-term care must be discussed (Level A), acknowledging that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults (Level B); no tests are shown to improve prognostic accuracy in children. Pain always should be assessed and treated (Level B) and evidence supporting treatment approaches discussed (Level B). Clinicians should prescribe amantadine (100-200 mg bid) for adults with traumatic VS/UWS or MCS (4-16 weeks post injury) to hasten functional recovery and reduce disability early in recovery (Level B). Family counseling concerning children should acknowledge that natural history of recovery, prognosis, and treatment are not established (Level B). Recent evidence indicates that the term chronic VS/UWS should replace permanent VS, with duration specified (Level B). Additional recommendations are included.

Comprehensive Systematic Review Update Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research.

OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days. METHODS: Articles were classified per the AAN evidence-based classification system. Evidence synthesis occurred through a modified Grading of Recommendations Assessment, Development and Evaluation process. Recommendations were based on evidence, related evidence, care principles, and inferences according to the AAN 2011 process manual, as amended. RESULTS: No diagnostic assessment procedure had moderate or strong evidence for use. It is possible that a positive EMG response to command, EEG reactivity to sensory stimuli, laser-evoked potentials, and the Perturbational Complexity Index can distinguish MCS from vegetative state/unresponsive wakefulness syndrome (VS/UWS). The natural history of recovery from prolonged VS/UWS is better in traumatic than nontraumatic cases. MCS is generally associated with a better prognosis than VS (conclusions of low to moderate confidence in adult populations), and traumatic injury is generally associated with a better prognosis than nontraumatic injury (conclusions of low to moderate confidence in adult and pediatric populations). Findings concerning other prognostic features are stratified by etiology of injury (traumatic vs nontraumatic) and diagnosis (VS/UWS vs MCS) with low to moderate degrees of confidence. Therapeutic evidence is sparse. Amantadine probably hastens functional recovery in patients with MCS or VS/UWS secondary to severe traumatic brain injury over 4 weeks of treatment. Recommendations are presented separately.

Early Fever As a Predictor of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is characterized by episodic, hyperadrenergic alterations in vital signs after traumatic brain injury (TBI). We sought to apply an objective scale to the vital sign alterations of PSH in order to determine whether 1 element might be predictive of developing PSH. SETTING/PARTICIPANTS/DESIGN: We conducted an observational study of consecutive TBI patients (Glasgow Coma Scale score ≤12) and monitored the cohort for clinical evidence of PSH. PSH was defined as a paroxysm of 3 or more of the following characteristics: (1) tachycardia, (2) tachypnea, (3) hypertension, (4) fever, (5) dystonia (rigidity or decerebrate posturing), and (6) diaphoresis, with no other obvious causation (ie, alcohol withdrawal, sepsis). MAIN MEASURES: The Modified Clinical Feature Severity Scale (mCFSS) was applied to each participant once daily for the first 5 days of hospitalization. RESULTS: Nineteen (11%) of the 167 patients met criteria for PSH. Patients with PSH had a higher 5-day cumulative mCFSS score than those without PSH (median [interquartile range] = 36 [29-42] vs 29 [22-35], P = .01). Of the 4 components of the mCFSS, elevated temperature appeared to be most predictive of the development of PSH, especially during the first 24 hours (odds ratio = 1.95; 95% confidence interval, 1.12-3.40). CONCLUSION: Early fever after TBI may signal impending autonomic dysfunction.

The need for VA leadership in advancing traumatic brain injury care.

Traumatic brain injury (TBI) afflicts veterans, active duty service members and the civilian community. An estimated 5.3 million US men, women, and children live with a permanent TBI-related disability. There is no cure for TBI, and the discovery of new and effective treatments is complicated by the fact that TBI is multifaceted and varies from individual to individual. Due to its established research centers, wealth of veteran health data, and commitment to veteran health, the VA should be considered a natural leader for expanded TBI research.

Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache.

Traumatic brain injury (TBI) is defined as an alteration in brain function caused by an external force. Mild TBI or concussion is now well recognized to be a risk of military service as well as participation in athletic sports such as football. Posttraumatic headache (PTH) is the most common symptom after mTBI in US service members. PTH most commonly presents with migraine-like headache features. The following is an overview of the epidemiology, pathophysiology, clinical course, prognosis, complications, and treatment of mTBI and associated comorbidities with a focus on PTH. There is a particular emphasis on emerging evidence-based clinical practice. One important medical consequence of the recognition that mTBI is a highly prevalent among military service members is that the Department of Defense (DoD) is dedicating significant financial and intellectual resources to better understanding and developing treatments for TBI. The identification of the importance of TBI among the US military population has had the added benefit of increasing awareness of this condition among civilian populations, particularly those engaged in both professional and youth sports. The NIH and NSF are also supporting important TBI research. President Obama's Brain Initiative is also providing additional impetus for these efforts. Unfortunately, the understanding of the acute and chronic effects of mTBI on the brain remains limited. Gratefully, there is hope that through innovative research, there will be advances in elucidating the underlying pathophysiology, which will lead to clinical and prognostic indicators, ultimately resulting in new treatment options for this very complicated set of disorders.

Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings.

Application of Tauroursodeoxycholic Acid for Treatment of Neurological and Non-neurological Diseases: Is There a Potential for Treating Traumatic Brain Injury?

The objective of this review was to evaluate the potential of tauroursodeoxycholic acid (TUDCA) for neuroprotection in traumatic brain injury (TBI) patients in the neurocritical care setting. Specifically, we surveyed preclinical studies describing the neuroprotective and systemic effects of TUDCA, and the potential therapeutic application of TUDCA. Preclinical studies have provided promising data supporting its use in neurological disease characterized by apoptosis-induced neuronal loss. TUDCA inhibits multiple proteins involved in apoptosis and upregulates cell survival pathways. In addition, TUDCA exhibits anti-inflammatory effects in models of neuroinflammation and attenuates neuronal loss in chronic neurodegenerative diseases. This may be applicable to TBI, which also triggers inflammatory and apoptotic processes. Additionally, preliminary data support the use of pharmacological therapies that reduce apoptosis and inflammation associated with TBI. The anti-apoptotic and anti-inflammatory mechanisms of TUDCA could prove promising in the treatment of TBI. Currently, there are no published data supporting improvement in clinical outcomes of TBI by treatment with TUDCA, but future studies should be considered.

Sleep disturbances in athletic concussion.

BACKGROUND: Sleep disturbances are a common symptom following concussions to include athletic concussion. REVIEW: This review applies literature on sleep following traumatic brain injury and concussion to sport concussions and places these considerations in the context of sleep and athletic performance. It also includes a description of sleep abnormalities in sleep duration, quality and timing as well as recommended treatment approaches. Finally, it includes a brief discussion of emerging paradigms of sleep and concussion recovery.

MRSI of the medial temporal lobe at 7 T in explosive blast mild traumatic brain injury.

PURPOSE: Up to 19% of veterans returning from the wars in Iraq and Afghanistan have a history of mild traumatic brain injury with 70% associated with blast exposure. Tragically, 20-50% of this group reports persistent symptoms, including memory loss. Unfortunately, routine clinical imaging is typically normal, making diagnosis and clinical management difficult. The goal of this work was to develop methods to acquire hippocampal MRSI at 7 T and evaluate their sensitivity to detect injury in veterans with mild traumatic brain injury. METHODS: At 7 T, hippocampal MRSI measurements are limited by: (1) poor B(0) homogeneity; (2) insufficient B(1)(+) strength and homogeneity; and (3) chemical shift dispersion artifacts. To overcofme these limitations we: (1) used third degree B(0) shimming; (2) an inductively decoupled transceiver array with radiofrequency shimming; and (3) a volume localized single slice sequence using radiofrequency shimming-based outer volume suppression. RESULTS: In 20 controls and 25 veterans with mild traumatic brain injury due to blast exposure with memory impairment, hippocampal N-acetyl aspartate to choline (P < 0.001) and N-acetyl aspartate to creatine (P < 0.001) were decreased in comparison to control subjects. CONCLUSION: With the appropriate methods robust spectroscopic imaging of the hippocampus can be carried out at 7 T. MRSI at 7 T can detect hippocampal injury in veterans with mild traumatic brain injury.

Moderate-to-severe traumatic brain injury.

Managing patients with moderate-to-severe traumatic brain injury (TBI), particularly those with combat-related blast injury, is exceptionally challenging. Optimal care requires the coordinated efforts of numerous providers, contributing to an interdisciplinary team. Given the complexities of TBI and the variety of physiologic, physical, cognitive, behavioral, and emotional manifestations of the injury, a holistic approach to patient care is needed throughout the entire continuum of care. In this article, the authors provide an overview of how interdisciplinary care is provided from the acute to the chronic settings, and illustrate the important role that rehabilitation plays throughout the continuum of care in facilitating maximizing recovery, functional independence, and quality of life. Common conditions associated with TBI are illustrated through a case presentation of an individual with blast-related polytrauma and help to frame a more detailed discussion of subtopics including neurointensive care, posttraumatic seizures, venous thromboembolic disease prevention, spasticity management, vestibular disorders, endocrine dysfunction, and psychological trauma.