User Tools

Site Tools


Traumatic brain injury (TBI)

Traumatic brain injury (TBI) is defined as a result of a bump, blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. This trauma can lead to temporary or permanent impairments of cognitive, physical and psychosocial functions, and an associated diminished or altered state of consciousness 1).



Risk Factors

Head impact direction has been identified as an influential risk factor in the risk of traumatic brain injury (TBI) from animal and anatomic research.

Increased risk of incurring a subdural hematoma exists from impacts to the frontal or occipital regions, and parenchymal contusions from impacts to the side of the head. There was no definitive link between impact direction and subarachnoid hemorrhage. In addition, the results indicate that there is a continuum of stresses and strain magnitudes between lesion types when impact location is isolated, with subdural hematoma occurring at lower magnitudes for frontal and occipital region impacts, and contusions lower for impacts to the side.

This hospital data set suggests that there is an effect that impact direction has on TBI depending on the anatomy involved for each particular lesion 2).


After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation.

Following TBI, various mediators are released which enhance vasogenic and/or cytotoxic brain edema. These include glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but no compound inhibiting mediators/mediator channels showed beneficial results in conducted clinical trials, despite successful experimental studies.

White matter injury is an important contributor to long term motor and cognitive dysfunction after traumatic brain injury. During brain trauma, acceleration, deceleration, torsion, and compression forces often cause direct damage to the axon tracts, and pathways that are triggered by the initial injury can trigger molecular events that result in secondary axon degeneration. White matter injury is often associated with altered mental status, memory deficits, motor or autonomic dysfunction, and contribute to the development of chronic neurodegenerative diseases. The presence and proper functioning of oligodendrocyte precursor cells offer the potential for repair and recovery of injured white matter. The process of the proliferation, maturation of oligodendrocyte precursor cells and their migration to the site of injury to replace injured or lost oligodendrocytes is known as oligodendrogenesis 3).


The neuropathology of traumatic brain injury (TBI) from various causes in humans is not as yet fully understood.

Penetrating head injury and closed head injury (CHI) that are moderate to severe are more likely than mild TBI (mTBI) to cause gross disruption of the cerebral vasculature. Axonal injury is classically exhibited as diffuse axonal injury (DAI) in severe to moderate CHI. Diffuse axonal injury is also prevalent in penetrating head injury (PHI). It is less so in mTBI. There may be a unique pattern of periventricular axonal injury in explosive blast mTBI. Neuronal injury is more prevalent in PHI and moderate to severe CHI than mTBI. Astrocyte and microglial activation and proliferation are found in all forms of animal TBI models and in severe to moderate TBI in humans. Their activation in mTBI in the human brain has not yet been studied 4).

Neurologic exam


The goals of imaging include:

(1) detecting injuries that may require immediate surgical or procedural intervention

(2) detecting injuries that may benefit from early medical therapy or vigilant neurologic supervision

(3) determining the prognosis of patients to tailor rehabilitative therapy or help with family counseling and discharge planning 5).

Missed or delayed detection of progressive neuronal damage and secondary brain damage after intracranial injuries may have a negative impact on the outcome of patients with traumatic brain injury (TBI) 6).

Although CT, MRI, and TCD were determined to be the most useful modalities in the clinical setting, no single imaging modality proved sufficient for all patients due to the heterogeneity of TBI. All imaging modalities demonstrated the potential to emerge as part of future clinical care 7).

Despite the obvious advantages of MRI in terms of delineating the extent and severity of brain injury, the MRI suite is not immediately accessible, and CT remains the modality of choice in the acute phase.

Due to its sensitivity to venous blood SWI is commonly used in traumatic brain injury (TBI)



CT imaging is limited by beam hardening effects, which can partially obscure the posterior fossa, temporal and frontal regions, and partial volume errors. The latter occur when a region of injured tissue has one or more dimensions that are smaller than the resolution of the acquired data 8). This can mean that haemorrhage or other evidence of intracranial pathology may remain undetected. Such issues are of particular concern within the brain stem and spinal cord, where a small area of pathology can result in devastating injury, and in many patients who exhibit evidence of diffuse axonal injury (DAI) after trauma. DAI is a frequent finding after TBI, accounting for up to 50% of trauma patients 9). The regions of the brain that are commonly injured include the grey–white matter interface, corpus callosum and deep white matter, periventricular and hippocampal areas, and brainstem 10). Such regions are best visualized using MRI 11).

Gradient echo MRI

Gradient echo MRI is sensitive to changes in magnetic susceptibility which results in lesions of low intensity after haemorrhage within the brain due to local magnetic field inhomogeneities caused by the paramagnetic properties of haemosiderin. By employing a variety of different MR sequences, the extent of brain injury can be demonstrated with high resolution across the brain.

Micro-hemorrhages are a common result of traumatic brain injury (TBI), which can be quantified with susceptibility weighted imaging and mapping (SWIM), a quantitative susceptibility mapping approach.


Blood tests

Unlike other organ-based diseases where rapid diagnosis employing biomarkers from blood tests are clinically essential to guide diagnosis and treatment, there are no rapid, definitive diagnostic blood tests for TBI. Over the last decade there has been a myriad of studies exploring many promising biomarkers. Despite the large number of published studies there is still a lack of any FDA-approved biomarkers for clinical use in adults and children. There is now an important need to validate and introduce them into the clinical setting 12).

Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl groups, indicating that markers of oxidative stress could be of predictive value for the selection of therapeutic strategies 13).


Traumatic brain injury is a significant cause of morbidity and mortality in children.

The use of prognostic models is becoming increasingly important in traumatic brain injury (TBI) research for baseline risk stratification in clinical trials and standardization of case-mix in comparative effectiveness research 14)

The traumatic brain injury (TBI) category accounted for the highest annual mean years of potential life lost (YPLL) at 361,748 (33.9% of total neurologic YPLL). Intracerebral hemorrhage, cerebral ischemia, subarachnoid hemorrhage, and anoxic brain damage completed the group of five diagnoses with the highest YPLL. TBI accounted for 12.1% of all inflation adjusted neurologic hospital charges and 22.4% of inflation adjusted charges among neurologic deaths. The in-hospital mortality rate has been stable or decreasing for all of these diagnoses except TBI, which rose from 5.1% in 1988 to 7.8% in 2011.

Missed or delayed detection of progressive neuronal damage after traumatic brain injury (TBI) may have negative impact on the outcome.

Wurmb et al, investigated whether routine follow-up CT is beneficial in sedated and mechanically ventilated trauma patients in a retrospective chart review. A routine follow-up cCT was performed 6 hours after the admission scan in 2 groups of patients, group I: patients with equal or recurrent pathologies and group II: patients with new findings or progression of known pathologies.

A progression of intracranial injury was found in 63 patients (42%) and 18 patients (12%) had new findings in cCT 2 (group II). In group II a change in therapy was found in 44 out of 81 patients (54%). 55 patients with progression or new findings on the second cCT had no clinical signs of neurological deterioration. Of those 24 patients (44%) had therapeutic consequences due to the results of the follow-up cCT.

They found new diagnosis or progression of intracranial pathology in 54% of the patients. In 54% of patients with new findings and progression of pathology, therapy was changed due to the results of follow-up cCT, concluding that in trauma patients who are sedated and ventilated for different reasons a routine follow-up CT is beneficial 15).

The mortality in severe TBI (STBI) ranges from 35 to 45% 16) 17) 18) 19).

Insurance and racial disparities continue to exist for TBI patients. Insurance status appears to have an impact on short- and long-term outcomes to a greater degree than patient race 20).

Quality of Life after Brain Injury


Cerebral contusion

Cerebral cortical contusions are one of the most common computed tomography (CT) findings in head injury 21) 22).

Brain edema

Brain edema can result from a combination of several pathological mechanisms associated with primary and secondary injury patterns in traumatic brain injury (TBI).

As pressure within the skull increases, brain tissue displacement can lead to brain herniation, resulting in disability or death.

see Anticoagulation in traumatic brain injury.

Harris et al, suggest a link between head injury and Parkinson's disease and indicates further scrutiny of workplace incurred head injuries is warranted 23).

Pituitary dysfunction

Posttraumatic epilepsy

Olfactory loss

Olfactory loss due to head trauma is a frequent finding. It is attributed to the tearing or severing of the olfactory fibers at the cribriform plate. In contrast, posttraumatic gustatory loss is observed and reported rarely and the underlying mechanism is less understood. Rahban et al. present a case of a concomitant post-traumatic anosmia and ageusia. Imaging showed a considerable frontobasal brain damage and it is speculated that the gustatory impairment is due to a central injury of the secondary taste cortex. Based on this observation, Rahban et al.we believe that this clinical presentation might be much more frequent than previously reported 24).

Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored.



Due to the marked heterogeneity of human traumatic brain injury (TBI), none of the available animal model can reproduce the entire spectrum of TBI, especially mild focal TBI.

A stereotaxic coupled weight drop device was designed. Principle arm of device carries up to 500g weights which their force was conveyed to animal skull through a thin nail like metal tip. To determine the optimal configuration of the device to induce mild TBI, six different trials were designed. The optimal configuration of the instrument was used for evaluation of behavioral, histopathological and molecular changes of mild TBI.

Neurologic and motor coordination deficits observed sharply within 24h post injury period. Histological studies revealed a remarkable increase in the number of dark neurons in trauma site. TBI increased the expression of apoptotic proteins, Bax, BCl2 and cleaved caspase-3 in the hippocampus.

This device is capable to produce variable severity of TBI from mild to severe. The main advantage of the new TBI model is induction of mild local unilateral brain injury instead of traumatization of the whole brain. This model does not require craniotomy for induction of brain injury.

This novel animal TBI model mimics human mild focal brain injury. This model is suitable for evaluation of pathophysiology as well as screening of new therapies for mild TBI 25).

Mechanical TBI models


Brain Injury Association of Tasmania

Brain Injury Network of South Australia

Brain Injury Association of NSW


The QOLIBRI-OS assesses a similar construct to the QOLIBRI total score and can be used as a brief index of HRQoL for traumatic brain injury TBI 26).

Case series


Cicuendez et al. retrospectively analyzed 264 TBI patients to whom a MR had been performed in the first 60 days after trauma. All clinical variables related to prognosis were registered, as well as the data from the initial computed tomography. The MR imaging protocol consisted of a 3-plane localizer sequence T1-weighted and T2-weighted fast spin-echo, FLAIR and gradient-echo images (GRET2*). Traumatic axonal injury (TAI) lesions were classified according to Gentry and Firsching classifications. They calculated weighted kappa coefficients and the area under the ROC curve for each MR sequence. A multivariable analyses was performed to correlate MR findings in each sequence with the final outcome of the patients.

TAI lesions were adequately visualized on T2, FLAIR and GRET2* sequences in more than 80% of the studies. Subcortical TAI lesions were well on FLAIR and GRET2* sequences visualized hemorrhagic TAI lesions. We saw that these MR sequences had a high inter-rater agreement for TAI diagnosis (0.8). T2 sequence presented the highest value on ROC curve in Gentry (0.68, 95%CI: 0.61-0.76, p<0.001, Nagerlkerke-R2 0.26) and Firsching classifications (0.64, 95%CI 0.57-0.72, p<0.001, Nagerlkerke-R2 0.19), followed by FLAIR and GRET2* sequences. Both classifications determined by each of these sequences were associated with poor outcome after performing a multivariable analyses adjusted for prognostic factors (p<0.02).

They recommend to perform conventional MR study in subacute phase including T2, FLAIR and GRET2* sequences for visualize TAI lesions. These MR findings added prognostic information in TBI patients 27).


634 consecutive neurosurgical trauma patients, who presented with mild-to-severe traumatic brain injury (TBI) from January 2013 to April 2014 at a tertiary care center in rural Nepal. All pertinent medical records (including all available imaging studies) were reviewed by the neurosurgical consultant and the radiologist on call. Patients' worst CT image scores and their outcome at 30 days were assessed and recorded. They then assessed their independent performance in predicting the mortality and also tried to seek the individual variables that had significant interplay for determining the same.

Both imaging score Marshall CT classification and Rotterdam CT score can be used to reliably predict mortality in patients with acute TBI with high prognostic accuracy. Other specific CT characteristics that can be used to predict early mortality are traumatic subarachnoid hemorrhage, midline shift, and status of the peri-mesencephalic cisterns.

They demonstrated in this cohort that though the Marshall CT classification has the high predictive power to determine the mortality, better discrimination could be sought through the application of the Rotterdam CT score that encompasses various individual CT parameters. They thereby recommend the use of such comprehensive prognostic model so as to augment the predictive power for properly dichotomizing the prognosis of the patients with TBI. In the future, it will therefore be important to develop prognostic models that are applicable for the majority of patients in the world they live in, and not just a privileged few who can use resources not necessarily representative of their societal environment 28).


Manual of Traumatic Brain Injury: Assessment and Management

Management of Adults With Traumatic Brain Injury

Understanding Traumatic Brain Injury: Current Research and Future Directions

Textbook of Traumatic Brain Injury

Brain Injury Medicine, 2nd Edition: Principles and Practice


Traumatic Brain Injury Center. (n.d.). Centers for Disease Control and Prevention. Retrieved May 1, 2012, from
Post A, Hoshizaki TB, Gilchrist MD, Brien S, Cusimano M, Marshall S. Traumatic Brain Injuries: The Influence of the Direction of Impact. Neurosurgery. 2015 Jan;76(1):81-91. PubMed PMID: 25525694.
Takase H, Washida K, Hayakawa K, Arai K, Wang X, Lo EH, Lok J. Oligodendrogenesis after traumatic brain injury. Behav Brain Res. 2016 Nov 6. pii: S0166-4328(16)30726-4. doi: 10.1016/j.bbr.2016.10.042. [Epub ahead of print] Review. PubMed PMID: 27829126.
de Lanerolle NC, Kim JH, Bandak FA. Neuropathology of Traumatic Brain Injury: Comparison of Penetrating, Nonpenetrating Direct Impact and Explosive Blast Etiologies. Semin Neurol. 2015 Feb;35(1):12-19. Epub 2015 Feb 25. PubMed PMID: 25714863.
Wintermark M, Sanelli PC, Anzai Y, Tsiouris AJ, Whitlow CT; ACR Head Injury Institute. Imaging Evidence and Recommendations for Traumatic Brain Injury: Conventional Neuroimaging Techniques. J Am Coll Radiol. 2014 Nov 25. pii: S1546-1440(14)00676-0. doi: 10.1016/j.jacr.2014.10.014. [Epub ahead of print] PubMed PMID: 25456317.
Becker DP, Miller JD, Ward JD. The outcome from severe head injury with early diagnosis and intensive management. Journal of Neurosurgery. 1977;47(4):491–502.
Pacifico A, Amyot F, Arciniegas D, Brazaitis MP, Curley K, Diaz-Arrastia R, Gandjbakhche A, Herscovitch P, Hinds SR, Manley GT M D Ph D, Razumovsky A, Riley J, Salzer W, Shih R, Smirniotopoulos JG, Stocker D. A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury. J Neurotrauma. 2015 Jul 15. [Epub ahead of print] PubMed PMID: 26176603.
Lee B, Newberg A. Neuroimaging in traumatic brain imaging. NeuroRx 2005;2:372-83.
9) , 10)
Hammoud DA, Wasserman BA. Diffuse axonal injuries: pathophysiology and imaging. Neuroimaging Clin N Am 2002;12:205-16.
Pierallini A, Pantano P, Fantozzi LM, et al. Correlation between MRI findings and long-term outcome in patients with severe brain trauma. Neuroradiology 2000;42:860-7.
Papa L, Edwards D, Ramia M. Exploring Serum Biomarkers for Mild Traumatic Brain Injury. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 22. PubMed PMID: 26269900.
Mendes Arent A, de Souza LF, Walz R, Dafre AL. Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury. Biomed Res Int. 2014;2014:723060. Epub 2014 Feb 13. Review. PubMed PMID: 24689052.
Maas AI, Murray GD, Roozenbeek B, et al. Advancing care for traumatic brain injury: findings from the IMPACT studies and perspectives on future research. Lancet Neurol. 2013;12(12):1200-1210.
Wurmb TE, Schlereth S, Kredel M, Muellenbach RM, Wunder C, Brederlau J, Roewer N, Kenn W, Kunze E. Routine follow-up cranial computed tomography for deeply sedated, intubated, and ventilated multiple trauma patients with suspected severe head injury. Biomed Res Int. 2014;2014:361949. doi: 10.1155/2014/361949. Epub 2014 Jan 20. PubMed PMID: 24563862.
Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81-4.
Mahapatra AK, Jindal A. Prognosis and outcome in Head Injury. In: Mahapatra AK, Rajkamal, editors. A textbook of head injury. 3 rd ed. New Delhi. CBS Publishers; 2005. p. 197-204.
Martins ET, Linhares MN, Sousa DS, Schroeder HK, Meinerz J, Rigo LA, et al. Mortality in severe traumatic brain injury: A multivariated analysis of 748 Brazilian patients from Florianópolis City. J Trauma 2009;67:85-90.
Lu J, Marmarou A, Choi S, Maas A, Murray G, Steyerberg EW. Impact and Abic Study Group. Mortality from traumatic brain injury. Acta Neurochir Suppl 2005;95:281-5.
Schiraldi M, Patil CG, Mukherjee D, Ugiliweneza B, Nuño M, Lad SP, Boakye M. Effect of Insurance and Racial Disparities on Outcomes in Traumatic Brain Injury. J Neurol Surg A Cent Eur Neurosurg. 2015 Mar 23. [Epub ahead of print] PubMed PMID: 25798799.
Becker DP, Miller JD, Ward JD, Greenberg RP, Young HF, Sakalas R. The outcome from severe head injury with early diagnosis and intensive management. J Neurosurg. 1977 Oct;47(4):491-502. PubMed PMID: 903803.
Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger J; Surgical Management of Traumatic Brain Injury Author Group.. Surgical management of traumatic parenchymal lesions. Neurosurgery. 2006 Mar;58(3 Suppl):S25-46; discussion Si-iv. Review. PubMed PMID: 16540746.
Harris MA, Shen H, Marion SA, Tsui JK, Teschke K. Head injuries and Parkinson's disease in a case-control study. Occup Environ Med. 2013 Dec;70(12):839-44. doi: 10.1136/oemed-2013-101444. Epub 2013 Sep 18. PubMed PMID: 24142978.
Rahban C, Ailianou A, Jacot E, Landis BN. [Concomitant anosmia and ageusia: a case report]. Rev Med Suisse. 2015 Sep 30;11(488):1787-90. French. PubMed PMID: 26619700.
Garjan TG, Sharifzadeh M, Khodagholi F, Musavi SM, Hasanzadeh G, Zarindast M, Gorji A. A novel traumatic brain injury model for induction of mild brain injury in rats. J Neurosci Methods. 2014 Jun 3. pii: S0165-0270(14)00203-9. doi: 10.1016/j.jneumeth.2014.05.035. [Epub ahead of print] PubMed PMID: 24906055.
von Steinbuechel N, Wilson L, Gibbons H, Muehlan H, Schmidt H, Schmidt S, Sasse N, Koskinen S, Sarajuuri J, Höfer S, Bullinger M, Maas A, Neugebauer E, Powell J, von Wild K, Zitnay G, Bakx W, Christensen AL, Formisano R, Hawthorne G, Truelle JL. QOLIBRI overall scale: a brief index of health-related quality of life after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2012 Nov;83(11):1041-7. doi: 10.1136/jnnp-2012-302361. Epub 2012 Jul 31. PubMed PMID: 22851609.
Cicuendez M, Castaño-León A, Ramos A, Hilario A, Gómez PA, Lagares A. [Magnetic resonance in traumatic brain injury: A comparative study of the different conventional magnetic resonance imaging sequences and their diagnostic value in diffuse axonal injury]. Neurocirugia (Astur). 2017 Jul 17. pii: S1130-1473(17)30070-2. doi: 10.1016/j.neucir.2017.06.001. [Epub ahead of print] Spanish. PubMed PMID: 28728755.
Munakomi S, Bhattarai B, Srinivas B, Cherian I. Role of computed tomography scores and findings to predict early death in patients with traumatic brain injury: A reappraisal in a major tertiary care hospital in Nepal. Surg Neurol Int. 2016 Feb 19;7:23. doi: 10.4103/2152-7806.177125. eCollection 2016. PubMed PMID: 26981324; PubMed Central PMCID: PMC4774167.
traumatic_brain_injury.txt · Last modified: 2018/06/23 10:56 by administrador