Official reprint from UpToDate

www.uptodate.com 2014 UpToDate

Traumatic brain injury: Epidemiology, classification, and pathophysiology
Authors
J Claude Hemphill, III, MD, MAS
Nicholas Phan, MD, FRCSC, FACS

Section Editor
Michael J Aminoff, MD, DSc

Deputy Editor
Janet L Wilterdink, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2014. | This topic last updated: Apr 13, 2013.
INTRODUCTION Traumatic brain injury (TBI) is the leading cause of death in North America for individuals between the
ages of 1 and 45. Many survivors live with significant disabilities, resulting in major socioeconomic burden as well. In 2000,
the economic impact of TBI in the United States was estimated to be $9.2 billion in lifetime medical costs and $51.2 billion
in productivity losses [1].
The focus of this topic is on the epidemiology, pathophysiology and classification of TBI. Other aspects of traumatic head
injury are discussed separately. (See "Management of acute severe traumatic brain injury" and "Concussion and mild
traumatic brain injury" and "Intracranial epidural hematoma in adults" and "Post-traumatic seizures and epilepsy" and
"Subdural hematoma in adults: Etiology, clinical features, and diagnosis" and "Skull fractures in adults".)
EPIDEMIOLOGY The overall incidence of TBI in the United States was estimated to be 538.2 per 100,000 population,
or around 1.5 million new cases in 2003 [1]. Somewhat lower rates are reported in Europe (235 per 100,000) and Australia
(322 per 100,000) [2,3].
Rates of TBI are highest in the very young (age group zero to four years) and in adolescents and young adults (15 to 24
years); there is another peak in incidence in the elderly (age >65 years) [1]. Approximately 78 percent of TBI are treated in
the emergency department only; 19 percent of patients require hospitalization, and 3 percent are fatal. Most cases treated
in emergency departments occur in the very young (ages zero to four years), while hospitalization rates are highest in
patients older than 65 years.
As with most traumatic injuries, the incidence of TBI is significantly higher in men compared to women, with ratios that vary
between 2.0 to 1 and 2.8 to 1 [4-6]. For severe TBI, the gender ratio is more pronounced, 3.5 to 1. Lower socioeconomic
status, and underlying psychiatric and cognitive disorders are also risk factors for head injury [7].
Falls are the leading cause of TBI (particularly in older patients), followed by motor vehicle accidents [6,8,9]. The
proportion of TBI secondary to violence has risen over the past decade and now accounts for 7 to 10 percent of cases
[10]. TBI related to military combat has received increased attention in the years from 2002 to 2009 [11]. Mechanistic
aspects of combat-related trauma may differ from TBI related to other causes, as the former usually involve blast
explosives.
Moderate and severe TBIs are associated with neurologic and functional impairments. The prevalence of long-term
disability related to TBI in the United States is variably estimated to be between 3.2 to 5.3 million, or approximately 1 to 2
percent of the population [12,13].
Epidemiologic trends more specific to mild TBI are discussed separately. (See "Concussion and mild traumatic brain
injury", section on 'Epidemiology'.)
CLASSIFICATION TBI is a heterogeneous disease. There are many different ways to categorize patients in terms of
clinical severity, mechanism of injury, and pathophysiology, each of which may impact prognosis and treatment.
The best prognostic models ideally include all of the factors described below, as well as age, medical comorbidity, and
laboratory parameters [14-16]. However, treatment decisions are likely best informed by considering these variables
individually rather than as a lump score. Further efforts at improved classification are ongoing as these may help to refine
treatment approaches [17].
Clinical severity scores TBI has traditionally been classified using injury severity scores; the most commonly used is
the Glasgow Coma Scale (GCS) (table 1) [18]. A GCS score of 13 to 15 is considered mild injury, 9 to 12 is considered
moderate injury, and 8 or less as severe traumatic brain injury.

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The GCS is universally accepted as a tool for TBI classification because of its simplicity, reproducibility, and predictive
value for overall prognosis. However, it is limited by confounding factors such as medical sedation and paralysis,
endotracheal intubation, and intoxication. These confounding issues are often particularly prominent in patients with a low
GCS score [19,20].
An alternative scoring system, the Full Outline of Unresponsiveness (FOUR) Score, has been developed in order to
attempt to obviate these issues, primarily by including a brainstem examination [21,22]. However, this lacks the long track
record of the GCS in predicting prognosis and is somewhat more complicated to perform, which may be a barrier for
nonneurologists [23].
Neuroimaging scales Traumatic brain injury can lead to several pathologic injuries, most of which can be identified on
neuroimaging [17]:
Skull fracture
Epidural hematoma
Subdural hematoma
Subarachnoid hemorrhage
Intraparenchymal hemorrhage
Cerebral contusion
Intraventricular hemorrhage
Focal and diffuse patterns of axonal injury with cerebral edema
Two currently used CT-based grading scales are the Marshall scale and the Rotterdam scale:
The Marshall scale uses CT findings to classify injuries in six different categories (table 2) [24]. It is widely used in
neurotrauma centers and has been shown to predict the risk of increased intracranial pressure and outcome in
adults accurately, but lacks reproducibility in patients with multiple types of brain injury.
The Rotterdam scale is a more recent CT-based classification developed to overcome the limitations of the Marshall
scale (table 3). It has shown promising early results but requires broader validation [25].
Other considerations There are other important considerations for prognosis and treatment in individuals with severe
traumatic brain injury.
Different disease mechanisms (eg, closed versus penetrating injuries, blast versus blunt trauma) may affect the type
of pathologic brain injury.
Extracranial injuries are present in about 35 percent of cases [26]. Multiple systemic traumatic injuries can further
exacerbate brain injury because of associated blood loss, hypoxia, and other related complications.
PATHOPHYSIOLOGY The pathophysiology of TBI-related brain injury is divided into two separate but related
categories: primary brain injury and secondary brain injury.
Current clinical approaches to the management of TBI center around these concepts of primary and secondary brain
injury. Surgical treatment of primary brain injury lesions is central to the initial management of severe head injury. Likewise,
the identification, prevention, and treatment of secondary brain injury is the principle focus of neurointensive care
management for patients with severe TBI. (See "Management of acute severe traumatic brain injury".)
Primary brain Injury Primary brain injury occurs at the time of trauma. Common mechanisms include direct impact,
rapid acceleration/deceleration, penetrating injury, and blast waves. Although these mechanisms are heterogeneous, they
all result from external mechanical forces transferred to intracranial contents. The damage that results includes a
combination of focal contusions and hematomas, as well as shearing of white matter tracts (diffuse axonal injury) along
with cerebral edema and swelling.

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Shearing mechanisms lead to diffuse axonal injury (DAI), which is visualized pathologically and on neuroimaging
studies as multiple small lesions seen within white matter tracts (image 1). Patients with severe DAI typically
present with profound coma without elevated intracranial pressure (ICP), and often have poor outcome. This
typically involves the gray-white junction in the hemispheres, with more severe injuries affecting the corpus callosum
and/or midbrain.
Focal cerebral contusions are the most frequently encountered lesions. Contusions are commonly seen in the basal

frontal and temporal areas, which are particularly susceptible due to direct impact on basal skull surfaces in the
setting of acceleration/deceleration injuries (image 2). Coalescence of cerebral contusions or a more severe head
injury disrupting intraparenchymal blood vessels may result in an intraparenchymal hematoma.
Extra-axial (defined as outside the substance of the brain) hematomas are generally encountered when forces are
distributed to the cranial vault and the most superficial cerebral layers. These include epidural, subdural, and
subarachnoid hemorrhage.
In adults, epidural hematomas (EDH) are typically associated with torn dural vessels such as the middle
meningeal artery, and are almost always associated with a skull fracture. EDHs are lenticular-shaped and tend
not to be associated with underlying brain damage. For this reason, patients who are found to have EDHs only
on CT scan may have a better prognosis than individuals with other traumatic hemorrhage types (image 3) [25].
Subdural hematomas (SDH) result from damage to bridging veins, which drain the cerebral cortical surfaces to
dural venous sinuses, or from the blossoming of superficial cortical contusions. They tend to be crescentshaped and are often associated with underlying cerebral injury (image 4).
Subarachnoid hemorrhage (SAH) can occur with disruption of small pial vessels and commonly occurs in the
sylvian fissures and interpeduncular cisterns. Intraventricular hemorrhage or superficial intracerebral
hemorrhage may also extend into the subarachnoid space.
Intraventricular hemorrhage is believed to result from tearing of subependymal veins, or by extension from
adjacent intraparenchymal or subarachnoid hemorrhage.
Approximately one-third of patients with severe TBI develop a coagulopathy, which is associated with an increased risk of
hemorrhage enlargement, poor neurologic outcomes and death [27-31]. While the coagulopathy may result from existing
patient medications such as warfarin or antiplatelet agents, acute TBI is also thought to produce a coagulopathy through
the systemic release of tissue factor and brain phospholipids into the circulation leading to inappropriate intravascular
coagulation and a consumptive coagulopathy [32].
Secondary brain Injury Secondary brain injury in TBI is usually considered as a cascade of molecular injury
mechanisms that are initiated at the time of initial trauma and continue for hours or days. These mechanisms include
[27,33-41]:
Neurotransmitter-mediated excitotoxicity causing glutamate, free-radical injury to cell membranes
Electrolyte imbalances
Mitochondrial dysfunction
Inflammatory responses
Apoptosis
Secondary ischemia from vasospasm, focal microvascular occlusion, vascular injury
These lead in turn to neuronal cell death as well as to cerebral edema and increased intracranial pressure that can further
exacerbate the brain injury. This injury cascade shares many features of the ischemic cascade in acute stroke. These
various pathways of cellular injury have been the focus of extensive preclinical work into the development of
neuroprotective treatments to prevent secondary brain injury in TBI. No clinical trials of these strategies have
demonstrated clear benefit in patients.
However, a critical aspect of ameliorating secondary brain injury after TBI is the avoidance of secondary brain insults,
which would otherwise be well-tolerated but can exacerbate neuronal injury in cells made vulnerable by the initial TBI.
Examples include hypotension and hypoxia (which decrease substrate delivery of oxygen and glucose to injured brain),
fever and seizures (which may further increase metabolic demand), and hyperglycemia (which may exacerbate ongoing
injury mechanisms). (See "Management of acute severe traumatic brain injury".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond
the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles are best for patients
who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are
best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to
your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)
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Basics topics (see "Patient information: Closed head injury (The Basics)")
SUMMARY Traumatic brain injury (TBI) encompasses a broad range of pathologic injuries to the brain of varying
clinical severity that result from head trauma.

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Among adults, TBI is most common in the young (<25 years), although there is another, smaller peak that occurs in
elder adults (>65 years). Motor vehicle accidents are a leading cause in younger adults, while falls are the most
likely cause of TBI in the older age group. (See 'Epidemiology' above.)
TBI is classically categorized as mild, moderate, and severe according to clinical severity using the Glasgow coma
scale (GCS) (table 1). (See 'Clinical severity scores' above.)
TBI can also be classified according to the type and severity of neuroimaging findings, the mechanism of brain
injury, and other variables. These factors individually, and in the aggregate, influence prognosis and treatment. (See
'Classification' above.)
The pathophysiology of TBI includes primary and secondary brain injury.
The pathoanatomical sequelae of primary TBI include intra- and extraparenchymal hemorrhages and diffuse
axonal injury. (See 'Primary brain Injury' above.)
Secondary TBI results from a cascade of molecular injury mechanisms, that are initiated at the time of initial
trauma and continue for hours or days. It is likely that secondary brain injury can be exacerbated by modifiable
systemic events such as hypotension, hypoxia, fever, and seizures. (See 'Secondary brain Injury' above.)
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Topic 4825 Version 9.0

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GRAPHICS
Glasgow coma scale
Score
Eye opening
Spontaneous

Response to verbal command

Response to pain

No eye opening

Best verbal response

Oriented

Confused

Inappropriate words

Incomprehensible sounds

No verbal response

Best motor response

Obeys commands

Localizing response to pain

Withdrawal response to pain

Flexion to pain

Extension to pain

No motor response

Total

The GCS is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of three
parameters: best eye response (E), best verbal response (V), and best motor response (M). The
components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS score of 9.
A score of 13 or higher correlates with mild brain injury; a score of 9 to 12 correlates with moderate
injury; and a score of 8 or less represents severe brain injury.
Graphic 81854 Version 2.0

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Marshall CT (computed tomography) classification of traumatic brain injury

Category

Definition

Diffuse injury I (no

visible pathology)

No visible intracranial pathology seen on CT scan

Diffuse injury II

Cisterns are present with midline shift of 0-5 mm and/or lesions densities
present; no high or mixed density lesion >25 cm 3 may include bone fragments
and foreign bodies

Diffuse injury III

(swelling)

Cisterns compressed or absent with midline shift 0-5 mm; no high or mixed
density lesion >25 cm 3

Diffuse injury IV (shift)

Midline shift >5 mm; no high or mixed density lesion >25 cm 3

Evacuated mass lesion

Any lesion surgically evacuated

V
Non-evacuated mass
lesion VI

High or mixed density lesion >25 cm 3; not surgically evacuated

Reproduced with permission from: Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical
management of severe traumatic brain injury in infants, children, and adolescents. Chapter 1: Introduction.
Pediatr Crit Care Med 2003; 4:S2. Copyright 2003 Lippincott Williams & Wilkins.
Graphic 67172 Version 10.0

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Rotterdam CT (computed tomography) classification of traumatic brain

injury
Predictor value

Score

Basal cisterns
Normal

Compressed

Absent

Midline shift
No shift or shift 5 mm

Shift >5 mm

Epidural mass lesion

Present

Absent

Intraventricular blood or subarachnoid hemorrhage

Absent

Present

Sum score

Total + 1

Reproduced with permission from: Maas Al, Hukkelhoven CW, Marshall LF, Steyerberg EW. 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 2005; 57:1173.
Copyright 2005 Lippincott Williams & Wilkins.
Graphic 70406 Version 11.0

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Diffuse axonal injury

CT scan of the brain showing diffuse axonal injury (DAI). Note the deep
shearing-type injury in or near the white matter of the left internal
capsule (arrow).
Reproduced with permission from: J Claude Hemphill II, MD and Nicholas
Phan, MD, FRCSC.
Graphic 67573 Version 3.0

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Frontal cerebral contusion

CT scan of the brain depicting cerebral contusions. The basal frontal

areas (as shown) are particularly susceptible.
Reproduced with permission from: J Claude Hemphill III, MD and Nicholas
Phan, MD, FRCSC.
Graphic 53951 Version 3.0

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TBI epidural hematoma

CT scan demonstrating a right epidural hematoma (EDH, arrow). Note

the lenticular shape.
Reproduced with permission from: J Claude Hemphill III, MD and Nicholas
Phan, MD, FRCSC.
Graphic 56200 Version 3.0

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TBI subdural hematoma

CT scan showing a left acute subdural hematoma (SDH, arrow).

Subdural hematomas are typically crescent-shape. In this case the SDH
is causing significant mass effect and shift of midline structures to the
right.
Reproduced with permission from: J Claude Hemphill III, MD and Nicholas
Phan, MD, FRCSC.
Graphic 68102 Version 3.0