Moderate and severe traumatic brain injury in adults

doi:10.1016/S1474-4422(08)70164-9

The Lancet Neurology

Volume 7, Issue 8, August 2008, Pages 728-741

https://doi.org/10.1016/S1474-4422(08)70164-9 Get rights and content

Summary

Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. In recent years, patterns of injury have been changing, with more injuries, particularly contusions, occurring in older patients. Blast injuries have been identified as a novel entity with specific characteristics. Traditional approaches to the classification of clinical severity are the subject of debate owing to the widespread policy of early sedation and ventilation in more severely injured patients, and are being supplemented with structural and functional neuroimaging. Basic science research has greatly advanced our knowledge of the mechanisms involved in secondary damage, creating opportunities for medical intervention and targeted therapies; however, translating this research into patient benefit remains a challenge. Clinical management has become much more structured and evidence based since the publication of guidelines covering many aspects of care. In this Review, we summarise new developments and current knowledge and controversies, focusing on moderate and severe TBI in adults. Suggestions are provided for the way forward, with an emphasis on epidemiological monitoring, trauma organisation, and approaches to management.

Introduction

Traumatic brain injury (TBI) constitutes a major health and socioeconomic problem throughout the world.1, 2 It is the leading cause of mortality and disability among young individuals in high-income countries, and globally the incidence of TBI is rising sharply, mainly due to increasing motor-vehicle use in low-income and middle-income countries. WHO has projected that, by 2020, traffic accidents will be the third greatest cause of the global burden of disease and injury.³ In higher income countries, traffic safety laws and preventive measures have reduced the incidence of TBI due to traffic accidents,⁴ whereas the incidence of TBI caused by falls is increasing as the population ages, leading to a rise in the median age of TBI populations (table 1). This has consequences for the type of brain damage currently seen, and contusions (falls in older patients) are becoming more frequent than diffuse injuries (high-velocity traffic accidents in younger patients).

Violence is now reported as the cause of closed head injury in approximately 7–10% of cases,9, 10 a substantial increase from earlier studies. The incidence of penetrating brain injury is also increasing, particularly in the USA, due to the use of firearms in violence-related injuries. Worldwide, armed conflicts and terrorist activities are causing more brain injuries, often due to improvised explosive devices, to the extent that blast injuries of the brain are now recognised as a specific entity. The changing patterns of injury and treatment approaches have challenged current concepts of classification. Moreover, basic research has greatly advanced our knowledge of what happens in the brain after TBI, offering opportunities to limit processes involved in secondary brain damage. However, translating advances from basic research into clinical benefit has proven complex. Here, we discuss current knowledge and novel insights and controversies in the study of adults with moderate and severe TBI, with the aim of integrating basic science and clinical research to provide guidelines on the epidemiological monitoring of TBI, trauma organisation, and management at the acute stage.

Section snippets

Epidemiology and cost

In the USA, monitoring by the Centers for Disease Control and Prevention shows the annual incidence of emergency department visits and hospital admissions for TBI to be 403 per 100 000 and 85 per 100 000, respectively.¹¹ Epidemiological data on TBI from the European Union are scarce, but do indicate an annual aggregate incidence of hospitalised and fatal TBI of approximately 235 per 100 000,¹² similar to that found in Australia,¹³ although substantial variation exists between European

Classification

TBI can be isolated, but is associated with extracranial injuries (limb fractures, thoracic or abdominal injuries) in about 35% of cases,¹⁹ which increases the risk of secondary brain damage due to hypoxia, hypotension, pyrexia, and coagulopathy. The recording of the severity of extracranial injuries should therefore form an integral part of TBI classification (panel).

Traditionally, TBI has been classified by mechanism (closed vs penetrating), by clinical severity (Glasgow coma scale [GCS]²⁰),

Primary damage

TBI is a heterogeneous disorder with different forms of presentation. The unifying factor is that brain damage results from external forces, as a consequence of direct impact, rapid acceleration or deceleration, a penetrating object (eg, gunshot), or blast waves from an explosion. The nature, intensity, direction, and duration of these forces determine the pattern and extent of damage.

On the macroscopic level, damage includes shearing of white-matter tracts, focal contusions, haematomas

Diagnosis

Head injury does not always implicate TBI. A diagnosis of TBI is established on the basis of clinical symptoms: for example, the presence of any documented loss of consciousness and/or amnesia (retrograde or post-traumatic). Additional clinical investigations can be driven by the patient's level of awareness, presence of risk factors, and mechanisms of injury (figure 2).

CT is the preferred method of assessment on admission to determine structural damage and to detect (developing) intracranial

Guidelines and individualised management

Over the past 10 years, much of the treatment of TBI has evolved towards standardised approaches that follow international and national guidelines (table 2). International guidelines for severe head injury are mostly evidence based, and address specific aspects of management. National guidelines focus more on organisational issues, such as admission and referral policy; however, these remain limited to the constraints of existing trauma systems, and clear statements on the best trauma

Pre-hospital emergency care

The main goals of prehospital management are to prevent hypoxia and hypotension, because these systemic insults lead to secondary brain damage.68, 81 When assessed before hospital admission (by ambulance or helicopter crews), oxygen saturation below 90% is found in 44–55% of cases and hypotension in 20–30%.81, 82, 83 Trauma renders the brain more vulnerable to these insults,⁸⁴ and hypoxia and hypotension are strongly associated with poor outcome (hypoxia: odds ratio [OR] 2·1, 95% CI 1·7–2·6;

Outcome and prognosis

Outcome after head injury is generally assessed at 6 months after injury, representing a compromise between true final outcome and logistic limitations. Experience shows that about 85% of recovery occurs within this time period, but further recovery can occur later. Accurate and consistent outcome determination at a fixed timepoint is a prerequisite for any TBI study. The most frequently used global outcome measure in TBI is the Glasgow outcome scale. More specific tools are required for

Neuroprotection and clinical trials

The original concept of neuroprotection involved the initiation of treatment before the onset of the event, and was aimed at minimising the intensity of an insult or its immediate effects on the brain by interrupting the harmful cascades of biochemical events. A major new focus of neurobiology now revolves around cell replacement, aimed at promoting neuroplasticity, and regeneration or replacement of lost neuronal and glial cells and neuronal circuits. Over the past 25 years, over 20 agents

Future directions

Here, we have illustrated the seriousness and complexity of the problems posed by TBI to patients, relatives, doctors, authorities, and society alike. Great advancements have been achieved over the past 10–15 years, but advances in basic science have not yet led to new treatments of clinically proven benefit, and advanced monitoring has not routinely resulted in individualised management. Current classification systems are no longer sufficient and not all patients have access to the best care.

Search strategy and selection criteria

References for this Review were identified through searches of PubMed, by use of the search terms “traumatic brain injury” or “head injury” and other appropriate targets, such as “epidemiology”, “pathophysiology”, and “guidelines”, up to May, 2008. Papers were also identified from the authors' own files and from references cited in relevant articles. An electronic search of resources, such as international and national guidelines and book chapters, was also done. The final reference list

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Decellularized brain extracellular matrix based NGF-releasing cryogel for brain tissue engineering in traumatic brain injury
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Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.
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Traumatic brain injury (TBI) is a major health concern globally, which is characterized by high morbidity and mortality rates. Since the 21st century, TBI has received increasing attention and the number of publications is growing rapidly. This study aimed to characterize the volume and quality of scholarly output on TBI and identify the most impactful literature, research trends, and hotspots from the year 2000–2022. We searched publications on TBI through the Web of Science Core Collection-Science Citation Index Expanded database which were published from 2000 to 2022. Basic information of each paper, including publication year, countries, authors, affiliations, journal, fundings, subject areas, and keywords were collected for further analysis by using Microsoft Excel, VOSviewer, and CiteSpace software. A total of 47231 TBI-related publications were identified through database retrieval. The annual number of publications on TBI has increased steadily over the past twenty years and the number in the year 2022 is sevenfold higher than that in 2000. The United States of America (USA) was the leading country in both numbers of publications and citations, which is consistent with the finding that it had the most funding agencies. Menon DK was the author with the highest influence and the University of California System was the most productive affiliation. Moreover, keywords analysis suggested that the research topics can be mainly divided into six categories: management, rehabilitation, mechanisms, concussion, neuroimaging, and neuroendocrine. This study visualized the trends and focuses of scientific research related to TBI, both quantitatively and qualitatively. The USA had a relatively high academic impact owing to its productive experts and institutions in this field. Neuroinflammation, machine learning, tranexamic acid, and extracellular vesicles are currently hot topics in the field of TBI.
Admission S100B fails as neuro-marker but is a good predictor for intrahospital mortality in major trauma patients
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S100 B is an extensively studied neuro-trauma marker, but its specificity and subsequently interpretation in major trauma patients might be limited, since extracerebral injuries are known to increase serum levels. Thus, we evaluated the potential role of S100B in the assessment of severe traumatic brain injury (TBI) in multiple injured patients upon emergency room (ER) admission and the first days of intensive care unit (ICU) stay.
Retrospective study employing trauma registry data derived from a level 1 trauma center. Four cohorts of patients were grouped: isolated TBI (iTBI), polytrauma patients with TBI (PT + TBI), polytrauma patients without TBI (PT-TBI) and patients without polytrauma or TBI (control). S100B-serum levels were assessed immediately after admission in the emergency room and during the subsequent ICU stay. Values were correlated with injury severity score (ISS), Glasgow Coma Score (GCS) and in-hospital mortality.
780 predominantly male patients (76 %) with a median age of 48 (30–63) and a median ISS of 24 (17–30) were enrolled in the study. Admission S100B correlated with ISS and TBI severity defined by the GCS (both p < 0.0001) but not with head abbreviated injury score (AIS) (p = 0.38). Compared with survivors, non-survivors had significantly higher median S100B levels in the ER (6.14 μg/L vs. 2.06 μg/L; p < 0.0001) and at ICU-day 1 (0.69 μg/L vs. 0.17 μg/L; p < 0.0001). S100B in the ER predicted mortality with an area under curve (AUC) of 0.77 (95 % CI 0,70–0,83, p < 0.0001), vs. 0.86 at ICU-day 1 (95 % CI 0,80–0,91, p < 0.0001).
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ReviewModerate and severe traumatic brain injury in adults

Summary

Introduction

Section snippets

Epidemiology and cost

Classification

Primary damage

Diagnosis

Guidelines and individualised management

Pre-hospital emergency care

Outcome and prognosis

Neuroprotection and clinical trials

Future directions

Search strategy and selection criteria

Lancet

Resuscitation

Lancet

Lancet

Exp Neurol

Lancet

Ophthalmology

J Clin Neurosci

Lancet

Chest

Global road safety crisis remedy sought: 1·2 million killed, 50 million injured annually

JAMA

The Traumatic Coma Data Bank; design, methods and baseline characteristics

J Neurosurg

Head injuries in four British neurosurgical centres

Br J Neurosurg

The European Brain Consortium survey of head injuries

Acta Neurochir (Wien)

Severe traumatic brain injury in Austria. I: Introduction to the study

Wien Klin Wochenschr

The prognostic value of cause of injury in traumatic brain injury: results from the IMPACT study

J Neurotrauma

Violent trauma in China: report of 2254 cases

Surg Neurol

Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths

A systematic review of brain injury epidemiology in Europe

Acta Neurochir (Wien)

Epidemiology of traumatic brain injury in South Australia

Brain Inj

Disability in young people and adults one year after head injury: prospective cohort study

BMJ

Cost estimation of injury-related hospital admissions in 10 European countries

J Trauma

Assessing the burden of injury in six European countries

Bull World Health Organ

Epidemiology and economics of head trauma

Brain research has high returns but Europe is lagging behind

Eur J Neurol

Mortality in patients with head injury and extracranial injury treated in trauma centers

J Trauma

A new classification of head injury based on computerized tomography

J Neurosurg

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years

J Neurol Neurosurg Psychiatry

Inaccurate early assessment of neurological severity in head injury

J Neurotrauma

Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors

Neurosurgery

Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients

BMJ

Prognostic modelling in traumatic brain injury

BMJ

Trauma

Traumatic brain injury in the war zone

N Engl J Med

Scientists: brain injuries from war worse than thought

USA Today

Blast-related traumatic brain injury: what is known?

J Neuropsychiatry Clin Neurosci

Wartime traumatic cerebral vasospasm: recent review of combat casualties

Neurosurgery

Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury

J Neurosurg

Coagulation disorders after traumatic brain injury

Acta Neurochir (Wien)

Autophagy is increased in mice after traumatic brain injury and is detectable in human brain after trauma and critical illness

Review
Moderate and severe traumatic brain injury in adults