The Science of Practice: Neurotrauma Review
The Egyptians in 2500 BC described spinal cord injury (SCI) as untreatable in the Edwin Smith Surgical Papyrus. For the next 4.5 millennia, the conventional wisdom did not change. It was not until luminaries like Dr. Donald Munro and Sir Ludwig Guttmann rejected this idea and introduced comprehensive SCI treatment that this condition went from fatal to treatable. Yet, neurotrauma remains a critical public health issue. Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in high-income countries.1 Fortunately, new trials and treatment algorithms have led to noteworthy progress in management over the last 150 years.
Mortality from neurotrauma has improved by 50 percent over the last 150 years, but there has been no improvement in mean mortality since 1990, which has remained stable at approximately 35 percent.1 Perhaps, the “low hanging fruit” has been plucked and harvested and now carefully researched guidelines are needed for further improvements/advancements. The recent 2017 guidelines for the management of Severe TBI 4th Edition aimed to synthesize available evidence and translate it into recommendations, although it is not intended to be a complete protocol for clinical use.2 The American College of Surgeons Trauma Quality Improvement Program did publish a detailed management outline for clinicians in 2017.3 This detailed synthesis of best practices covers the appropriate use of the Glasgow Coma Scale, surgical management, special populations and outcome assessment.
Beyond codifying current knowledge and disseminating it, numerous trials are underway to optimize TBI management from the bench, bedside and community. One of the most well-known recent advancements in neurotrauma is the demonstration of chronic traumatic encephalopathy (CTE) in contact-sport athletes and in military veterans with blast injuries.4 The neuropathology and pathogenesis of CTE espoused by the McKee criteria expanded current CTE understanding and consequently influenced school sports and National Football League rules.
Additionally, the Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (BOOST II) trial supported algorithms that minimize hypoxia and ischemia following severe TBI.5 By employing a multimodal LiCOX brain tissue oxygenation (pBrO2) monitoring and intracranial pressure device, it was possible to reduce the fraction of time that brain oxygen levels are below the critical threshold of 20 mm Hg, thus leading to lower mortality and favorable outcomes. Heightened neuropathology knowledge and pre-hospital resuscitation have impacted ICU practices in an attempt to minimize hypoxic brain damage, which is a key cornerstone of TBI management. Lastly, the NINDS-funded “Transforming Research and Clinical Knowledge in TBI” (TRACK-TBI) study is the largest funded (about $60 million) neurosurgical research endeavor in history. The goal is to collect detailed clinical data from 3,000 TBI subjects at 18 Level 1 trauma center sites across the United States. By using megadata and informatics, the study will improve TBI classification, outcome assessments and costs of clinical trials, while quantifying the health/economic impact of mild TBI. TRACK-TBI will effectively “reboot” TBI management by sifting through individual management protocols in order to identify best practices.
Trials are also efficacious in identifying and avoiding harmful management practices. The Corticosteroid Randomization After Significant Head injury (CRASH) trial analyzed the effects of early steroid use in head injury patients.7 The results demonstrated that steroids should not be employed in the treatment of acute TBI. Trials such as the North American Brain Injury Study: Hypothermia II (NABIS:H II) and the European Study of Therapeutic Hypothermia for Intracranial Pressure Reduction after Traumatic Brain Injury (Eurotherm3235) tested therapeutic hypothermia for intracranial pressure reduction in patients with severe TBI.8,9 These trials failed to confirm the utility of hypothermia as a primary neuroprotective intervention. However, the severe and lasting sequelae of mild TBI have been correlated with mild elevations in brain temperature.10 As a result, hyperthermia has also been found to be harmful and should be strictly avoided in TBI cases.
Worldwide, varying levels of available resources constrain regions in their ability to curtail the public health issue of neurotrauma. With the cohesive force of the North American Clinical Trials Network (NACTN), discoveries may be disseminated internationally. Public policy intervention has the potential to bolster primary prevention in areas in which secondary and tertiary prevention practices are unavailable. Ultimately, the scientific discoveries of research trials must be translated into useful practice algorithms. Guidelines may aid in the creation of such algorithms, but alone they are not sufficient to further decrease the burden of neurotrauma.
Clearly, the neurotrauma field has advanced beyond recognizing futile cases to refining the best medical practices. Ideally, the support of substantive scientific research and the dissemination of evidence-based practices will further diminish the morbidity and mortality of neurotrauma.
ReferencesClick to View All
1. Stein SC, Georgoff P, Meghan S, Mizra K, Sonnad SS. 150 years of treating severe traumatic brain injury: a systematic review of progress in mortality. J Neurotrauma. 2010;27(7):1343-1353.
2. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017;80(1):6-15.
3. Gill Cryer, H & , FACS & T. Manley, Geoffrey & David Adelson, P & Alali, Aziz & Calland, M.D., James & Cipolle, Mark & Cribrari MD FACS, Christopher & L. Davis, Matthew & Hemmila, Mark & Claude Hemphill, J & Huang, Michael & Jawa, Randeep & Kilbaugh, Todd & Kozar, Rosemary & Maas, Andrew & Merck, Lisa & Wright, David. (2015). American College of Surgeons Trauma Quality Improvement Program Guidelines, Traumatic Brain Injury. Committee on Trauma Expert Panel 1/2015, American College of Surgeons.
4. McKee AC, Abdolmohammadi B, Stein TD. The neuropathology of chronic traumatic encephalopathy. Handb Clin Neurol. 2018;158:297-307.
5. Okonkwo DO, Shutter LA, Moore C, et al. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017;45(11):1907-1914.
6. “Track-TBI & TED.” One Mind, onemind.org/research/tracktbi/.
7. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321-1328.
8. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011;10(2):131-139.
9. Andrews PJ, Sinclair HL, Rodriguez A, et al. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury. N Engl J Med. 2015;373(25):2403-2412.
10. Truettner JS, Bramlett HM, Dietrich WD. Hyperthermia and Mild Traumatic Brain Injury: Effects on Inflammation and the Cerebral Vasculature. J Neurotrauma. 2018.
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