Interventional Treatment of Symptomatic Vasospasm in the Setting of Traumatic Brain Injury: A Systematic Review of Reported Cases.

Traumatic subarachnoid hemorrhage (tSAH) is frequently comorbid with traumatic brain injury (TBI) and may induce secondary injury through vascular changes such as vasospasm and subsequent delayed cerebral ischemia (DCI). While aneurysmal SAH is well studied regarding vasospasm and DCI, less is known regarding tSAH and the prevalence of vasospasm and DCI, the consequences of vasospasm in this setting, when treatment is indicated, and which management strategies should be implemented. In this article, a systematic review of the literature that was conducted for cases of symptomatic vasospasm in patients with TBI is reported, association with tSAH is reported, risk factors for vasospasm and DCI are summarized, and commonalities in diagnosis and management are discussed. Clinical characteristics and treatment outcomes of 38 cases across 20 studies were identified in which patients with TBI with vasospasm underwent medical or endovascular management. Of the patients with data available for each category, the average age was 48.7 ± 20.3 years (n = 31), the Glasgow Coma Scale score at presentation was 10.6 ± 4.5 (n = 35), and 100% had tSAH (n = 29). Symptomatic vasospasm indicative of DCI was diagnosed on average at postinjury day 8.4 ± 3.0 days (n = 30). Of the patients, 56.6% (n = 30) had a new ischemic change associated with vasospasm confirming DCI. Treatment strategies are discussed, with 11 of 12 endovascularly treated and 19 of 26 medically treated patients surviving to discharge. tSAH is associated with vasospasm and DCI in moderate and severe TBI, and patients with clinical and radiographic evidence of symptomatic vasospasm and subsequent DCI may benefit from endovascular or medical management strategies.

Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction.

Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain's vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.

Acupuncture and Spinal Stenosis: Considerations for Treatment.

Acupuncture has been a staple of Eastern medicine for thousands of years. Recent evidence has shown that benefits for spinal stenosis are strong. In this comprehensive review, we overview the history and available literature. We discuss how the techniques have evolved and the clinical utility. The process and progression of spinal stenosis is addressed. We discuss mechanism of action for acupuncture as well as relevant treatment implications. This is important in alleviating pain and providing strong quality of life. We highlight both the findings in the pre-operative, peri-operative, and post-operative periods. Finally, the pre-clinical data provides compelling evidence in terms of novel pathways being targeted. This resource will serve as a user-friendly guide for the clinician and scientist regarding this important topic. It will be the catalyst of ongoing investigation from both the clinical and pre-clinical side.

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents.

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI. Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment.

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB's role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes.

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders.

The potential dangers of neck manipulation & risk for dissection and devastating stroke: An illustrative case & review of the literature.

Chiropractic cervical manipulation is a common practice utilized around the world. Most patients are never cleared medically for manipulation, which can be devastating for those few who are at increased risk for dissections. The high velocity thrust used in cervical manipulation can produce significant strain on carotid and vertebral vessels. Once a dissection has occurred, the risk of thrombus formation, ischemic stroke, paralysis, and even death is drastically increased. In this case report, we highlight a case of a 32-year-old woman who underwent chiropractic manipulation and had vertebral artery dissection with subsequent brainstem infarct. She quickly deteriorated and passed away shortly after arrival to the hospital. Although rare, one in 48 chiropractors have experienced such an event. We utilize this case to highlight the risk associated with cervical manipulation and urge open dialogue between chiropractors and physicians. Receiving medical clearance prior to cervical manipulation in potential at risk patients would drastically reduce morbidity and mortality.

Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy.

The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3ß (GSK-3ß), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury.

Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.

In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2+ BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM.

Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

Crisis Management Simulation: Establishing a Dual Neurosurgery and Anesthesia Training Experience.

BACKGROUND: Simulation training has been shown to be an effective teaching tool. Learner management of an intraoperative crisis such as a major cerebrovascular bleed requires effective teamwork, communication, and implementation of key skill sets at appropriate time points. This study establishes a first of a kind simulation experience in a neurosurgery/anesthesia resident (learners) team working together to manage an intraoperative crisis. METHODS: Using a cadaveric cavernous carotid injury perfusion model, 7 neurosurgery and 6 anesthesia learners, were trained on appropriate vascular injury management using an endonasal endoscopic technique. Learners were evaluated on communication skills, crisis management algorithms, and implementation of appropriate skill sets at the right time. A preanatomic and postanatomic examination and postsimulation survey was administered to neurosurgery learners. Anesthesia learners provided posttraining evaluation through a tailored realism and teaching survey. RESULTS: Neurosurgery learners' anatomic examination score improved from presimulation (33.89%) to postsimulation (86.11%). No significant difference between learner specialties was observed for situation awareness, decision making, communications and teamwork, or leadership evaluations. Learners reported the simulation realistic, beneficial, and highly instructive. CONCLUSIONS: Realistic, first of kind, clinical simulation scenarios were presented to a neurosurgery/anesthesia resident team who worked together to manage an intraoperative crisis. Learners were effectively trained on crisis management, the importance of communication, and how to develop algorithms for future implementation in difficult scenarios. Learners were highly satisfied with the simulation training experience and requested that it be integrated more consistently into their residency training programs.

The Effect of Sporting Events on Medical Transport Time at a Level 1 Trauma Center: a Retrospective Cohort Study.

OBJECTIVE: We investigate how West Virginia University football games affect transport to Ruby Memorial Hospital, which shares a parking lot with Milan Puskar Football Stadium. METHODS: A retrospective chart review of a trauma registry from a level 1-trauma center was conducted from 2007 to 2011 for all home and away football games. Home games served as time period of interest and away games served as a control time period. Patient charts were collected for a 36-hour time window surrounding the game. 250 patient charts were complete for home games and 185 patient charts for away games. Data analyzed were time from scene to arrival at hospital, use of air transport, transport time in relation to kick-off, and comparison between demographic and emergency department disposition of patients arriving during home games vs. patients arriving during away games. RESULTS: No statistically significant differences were found for demographic data or emergency department disposition between groups. For ground transport directly from scene, the average time to arrival at the hospital was 44.9 minutes for home games and 45.1 minutes for away games. For air transport directly from the scene, the average time to arrival at the hospital was 44.9 minutes for home games and 44.0 minutes for away games. For ground transfer from another facility, the average time to arrival at the hospital was 76.4 minutes for home games and 52.9 minutes for away games. For air transport from another facility, the average time to arrival at the hospital was 37.4 minutes for home games and 24.0 minutes for away games. Air transportation utilization was increased in inter-facility transfers during home games (5/16, 31.3% vs. 4/20, 22.2%), and helicopters traveled a further distance (avg. 66.6 vs. 50.25 air miles). For patients coming from the scene during a home game, if the start of the game occurred after the trauma but before arrival to the trauma center, the average time of ground transport increased from 44.9 minutes to 120 minutes (p<0.0001). CONCLUSION: A mass gathering in close proximity to a rural trauma center does affect transport patterns and transport times for trauma patients. Further investigation is warranted in order to improve patient care during mass gathering events.

A mouse Model of Focal Vascular Injury Induces Astrocyte Reactivity, Tau Oligomers, and Aberrant Behavior.

Neuropsychiatric symptom development has become more prevalent with 270,000 blast exposures occurring in the past 10 years in the United States. How blast injury leads to neuropsychiatric symptomology is currently unknown. Preclinical models of blast-induced traumatic brain injury have been used to demonstrate blood-brain barrier disruption, degenerative pathophysiology, and behavioral deficits. Vascular injury is a primary effect of neurotrauma that can trigger secondary injury cascades and neurodegeneration. Here we present data from a novel scaled and clinically relevant mouse blast model that was specifically developed to assess the outcome of vascular injury. We look at the biochemical effects and behavioral changes associated with blast injury in young-adult male BALB/c mice. We report that blast exposure causes focal vascular injury in the Somatosensory Barrel Field cortex, which leads to perivascular astrocyte reactivity, as well as acute aberrant behavior. Biochemical analysis revealed that mild blast exposure also invokes tauopathy, neuroinflammation, and oxidative stress. Overall, we propose our model to be used to evaluate focal blood-brain barrier disruption and to discover novel therapies for human neuropsychiatric symptoms.

Corrigendum to "Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms".

[This corrects the article DOI: 10.1155/2016/8781725.].

Primary Endovascular Repair of Ilio-Caval Injury Encountered during Anterior Exposure Spine Surgery: Evolution of the Paradigm.

BACKGROUND: Rates of major venous injury are now being reported at between 1% and 15%. Risk factors for injury include the previous spine surgery, level of exposure, and number of retractors used. To review and describe the evolution of our use of stent grafts for repair of life-threatening ilio-caval injuries encountered during anterior exposure lumbosacral (L-S) spine surgery from rescue utilization after failed direct repair to preferred modality using occlusion balloons and covered stents akin to the modern management of the ruptured abdominal aortic aneurysm (AAA) with endovascular aneurysm repair. METHODS: Five-year retrospective review of all anterior and retroperitoneal spine procedures was performed at our institution. RESULTS: One hundred two procedures were done. Major ilio-caval injury occurred in 3/102 (2.9%) cases. Average blood loss per case decreased as our approach evolved from unsuccessful direct open repair with percutaneous endovascular rescue to primary percutaneous endovascular repair. All treated patients had patent venous repair in short-term follow-up with computed tomography angiography. CONCLUSIONS: Identification and rapid direct repair of major ilio-caval injuries during anterior approach spine surgery can be extremely challenging. When control of these potentially fatal injuries is required, our choice is primary endovascular repair using the modern techniques for endovascular management of ruptured AAA with endovascular aneurysm repair.

Blast Scaling Parameters: Transitioning from Lung to Skull Base Metrics.

Neurotrauma from blast exposure is one of the single most characteristic injuries of modern warfare. Understanding blast traumatic brain injury is critical for developing new treatment options for warfighters and civilians exposed to improvised explosive devices. Unfortunately, the pre-clinical models that are widely utilized to investigate blast exposure are based on archaic lung based parameters developed in the early 20th century. Improvised explosive devices produce a different type of injury paradigm than the typical mortar explosion. Protective equipment for the chest cavity has also improved over the past 100 years. In order to improve treatments, it is imperative to develop models that are based more on skull-based parameters. In this mini-review, we discuss the important anatomical and biochemical features necessary to develop a skull-based model.

Successful Treatment of Symptomatic Intracranial Carotid Artery Stenosis Using a 24-mm Long Bare Metal Coronary Stent.

BACKGROUND: Intracranial arterial atherosclerosis represents a common cause of stroke. Despite aggressive and optimal medical management, many patients will unfortunately suffer additional cerebrovascular events. The role of endovascular intervention for intracranial atherosclerotic disease continues to be uncertain, particularly in regard to extensive, symptomatic stenosis. CASE DESCRIPTION: We present a case of a 42-year-old man with a complex medical history who presented with recurrent ischemic stroke in the ipsilateral hemisphere despite optimal medical management. Given the length of stenosis and the luminal size of the intracranial cavernous and petrous segments of the internal carotid artery, we used a bare metal coronary stent (4.0 mm × 24 mm). This represents one of the longest stents deployed for intracranial disease reported in the literature. CONCLUSIONS: This case illustrates that a long coronary stent might be successfully used to manage extensive intracranial lesions. We also review the efficacy of using 1 very long stent versus multiple overlapping stents, with reference to the coronary angiography literature.