The purpose of this chapter is to review current epidemiology of traumatic brain injury (TBI) and classify the different types of TBI according to underlying pathology. For the purpose of this review, TBI is defined as “a traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force.” Examples of such injuries include head strike by an object, rapid acceleration/deceleration-related injuries with damage to brain tissue, and penetration by a foreign body which induces brain injury. TBI is characterized by new onset or worsening of at least one of the following clinical signs or symptoms immediately following the event:
Any period of loss or a decreased level of consciousness (LOC)
Any loss of memory for events immediately before or after the injury (i.e., post-traumatic amnesia)
Any alteration in mental state at the time of injury (i.e., confusion, disorientation, slowed thinking)
Neurologic deficits (i.e., weakness, loss of balance, change in vision, praxis, sensory loss, aphasia) that may or may not be transient
The ever-growing body of epidemiological studies contributes to our current understanding of TBI. Worldwide, the incidence of TBI is 235 to 556 per 100,000 people. Data released in 2015 by the Centers for Disease Control and Prevention (CDC) and the National Center for Injury Prevention and Control (NCIPC)1 reported that approximately 1.7 million traumatic brain injuries annually. Eighty percent of these cases were reported from emergency department (ED) visits and 16.3% (275,000) from hospitalization. Three percent (52,000) resulted in death. In the United States, TBI comprises 30.5% of all injury-related deaths. According to the same CDC/NCIPC report, the total combined rates of TBI-related ED visits, hospitalizations, and deaths have increased from 521.0/100,000 in 2001 to 823.7/100,000 in 2010. This is largely due to the proportionate rise of ED visits in comparison to hospitalizations and deaths. It has been proposed that a greater awareness of TBI is what caused an increase in ED visits. In terms of prevalence, approximately 5.3 million individuals are living with TBI and its sequelae currently in the United States.
There are several striking gender differences among those with TBI. Rates are higher for males than for females, at a ratio of 2.5:1, and mortality rates in males are three to four times greater.
Regarding age, the populations most likely to sustain a TBI include 0 to 4 years, 15 to 19 years, and 65 years and older. The highest rates of death occur in those aged 65 and older. The age group with the highest rate of TBI-related ED visits is 0 to 14 years, and the age group with the highest rate of TBI-related hospitalizations occurs in patients greater than 65 years.
Causes of TBI have been found to vary with the different age groups. The National Hospital Ambulatory Medical Care Survey on Emergency Department Visits (2006–2010) characterizes the primary injury mechanism underlying TBI-related deaths by age. Interestingly, self-inflicted causes are the most common in patients between the ages of 24 and 64 years of age (Table 20–1).
The permanent or temporary impairments stemming from a TBI influence cognitive, physical, and psychosocial functions. These functional deficits create a significant burden which affects the individual, the caretaker, and beyond. From the perspective of global burden, TBI represents the leading cause of morbidity and mortality worldwide in individuals under age 45 years. The World Health Organization (WHO) reports an estimated 10 million individuals suffer a TBI annually. By 2020, the WHO predicts TBIs will be the third largest contributor to the global burden of disease and mortality. From the perspective of an economic burden, the CDC reports that the estimated economic cost of TBI in 2010, including direct and indirect costs, approximated $76.5 billion; furthermore, mild TBIs alone cost the United States roughly $US17 billion per year.
A penetrating TBI is defined as an injury to the brain due to the intrusion of a foreign object (e.g., bullet, shrapnel, debris) into the cranium. It is less common than blunt, or nonpenetrating, injury. Gunshot wounds to the head have become among the leading causes of head injury in many cities in the United States. Recent conflicts in the Iraq War and Afghanistan War have seen a higher prevalence of penetrating injuries compared to nonpenetrating injuries, with ratios in these confrontations of 2:1 and 1.3:1, respectively.1 Patients suffering from a penetrating brain injury have been found to have a thirty-fivefold increase in mortality when compared to those experiencing a nonpenetrating brain injury.2 Penetrating TBI confers a higher incidence of low Glasgow Coma Scale (GCS) scores, and patients who suffer from penetrating TBI are more likely to be younger, less educated, nonwhite, unmarried, and male. They are also more likely to have problems with substance abuse, longer duration of post-traumatic amnesia, and longer hospital stays.3
Penetrating head injuries can be the result of numerous intentional or unintentional events, including shrapnel, motor vehicle, and occupational accidents (nails, screwdrivers, machinery, etc.). Assaults are also a cause of penetrating head injury, with knife stab wound being the most common form of penetrating injury due to assault. The velocity of the penetrating object is important for the pathophysiology, treatment, and prognosis of injury; higher-velocity penetrating objects lead to lower chances of survival and poorer prognosis.
Several factors directly contribute to the extent of damage found after a penetrating head injury. These key factors include the object’s trajectory through the brain, the object’s kinetic energy, and secondary mechanisms of injury (explained later). TBI can be divided into primary and secondary injury that can be further divided into three phases.
The acute phase of penetrating brain injury (primary phase 1 injury) is characterized by mechanical damage (i.e., shearing and tearing) of blood vessels, which leads to subdural and/or intracranial hematomas. Key concepts underlying phase 1 injury include primary contact by object, cavitation, and shock waves caused by the object’s trajectory through the brain. Initial contact of the projectile to the skull causes a brief shock wave that then transfers disruptive, high magnitudes of kinetic energy to adjacent tissues, including neurons, glial cells, and cerebrovasculature. The projectile compresses the medium directly in front of it, thereby creating a hollowing along its track. This cavity further expands due to cycles of stretching and collapse caused by direct transfer of energy. While phase 1 of penetrating brain injury is unique, the hallmark of primary phase 1 TBI is direct and acute trauma to brain matter.
Secondary brain injury in any form of TBI includes phases 2 and 3. Phase 2 is a subacute result of initial injury and is characterized by the release of cytotoxic metabolites that further increase cerebral edema, causing an increase in intracranial pressure and leading to cerebral ischemia. Phase 2 then progresses into immune system activation of microglia and triggers astrogliosis, recruitment of inflammatory mediators such as neutrophils and macrophages, and release of proinflammatory cytokines leading to further tissue damage. Phase 3 is characterized by axonal degeneration. It begins 72 hours after insult and is caused by the neuroinflammatory response and neurodegenerative effects of phase 2. More specifically, it is a result of C5b-9/MAC complexes formed by the release of complement proteins through a disrupted blood–brain barrier. Another proposed model for the penetrating brain injury cascade can be summarized in Table 20–2.4,5
| Phase | Time Frame | Pathophysiology |
| Phase 1 | 0–6 hours | Rapid elevation in intracranial pressure and thus reduction in cerebral perfusion pressure. |
| Phase 2 | 6–72 hours | Loss of blood–brain barrier, infiltration of peripheral granulocytes. Also, secondary necrosis, apoptosis and start of axonal degeneration. |
| Phase 3 | Day 3–7 | Remote neurodegeneration and scar formation by reactive astrocytes. |
Clinical presentation depends on the specific mechanism of penetrating injury and the anatomic area affected. Generally, penetrating injuries cause circumscribed cognitive impairment; however, it is important to note that diffuse impairment is also possible following a penetrating brain injury. Hypersomnia has been found to occur after severe penetrating brain injury, yet it may resolve within the first year. Post-traumatic amnesia (PTA) is a hallmark finding in any TBI, including penetrating TBI. PTA can be divided into retrograde and anterograde amnesia. The first is defined as inability to recall events immediately preceding the traumatic event that led to the TBI. The latter is defined as the inability to form new memories following said traumatic event. A patient may have both retrograde and anterograde PTA, and duration of PTA is considered one of the most important predictors of prognosis following TBI. Those persons who suffer longer periods of PTA have poorer prognosis.
Establishing the anatomic area of the injury plays a major role in treatment and prognosis. Noncontrast computed tomography (CT) of the head is the initial test of choice for patients presenting with penetrating brain injury. Plain radiographs of the skull can aid in visualizing cranial wounds as well as the presence and location of metal and bone fragments and of intracranial air.6 However, skull radiographs are not considered first-line imaging in the setting of TBI.
If magnetic resonance imaging (MRI) of the brain is necessary, CT or x-ray must be used prior to exclude the presence of ferromagnetic/metal objects. It is important to note that not all bullets are made of ferromagnetic materials. MRIs performed in the presence of intracerebral ferromagnetic objects may cause injury to the brain. A risk versus benefit approach should be utilized prior to performing MRI studies for patients with foreign metal objects in their central nervous system. The ordering physician should discuss the case with a radiologist to assess the need and safety of an MRI. In cases where a vascular injury is suspected, CT angiography of head and neck should be used for evaluation.
Urgent resuscitation, correction of coagulopathy, and early surgery with cranial decompression may improve outcomes for severe penetrating brain injuries.7 Surgical management includes wound and necrotic tissue debridement and hematoma evacuation. The extent of surgical intervention is dependent on the degree of the injury. Patients may benefit from craniotomy, craniectomy, or other surgery which relieves increased intracranial pressure (ICP) after penetrating brain injury. Hematomas localized to the temporal and posterior fossae have a higher risk for herniation and therefore warrant more aggressive surgical management.
Surgical removal of projectiles contained fully within the brain is not recommended, as it confers worse prognosis and higher morbidity.8 Aggressive debridement and prophylaxis with broad-spectrum antibiotics are standard of care in such cases.
Patients suffering from a penetrating head injury may display similar complications observed in other types of traumatic brain injury. Among these, post-traumatic cerebral vasospasm, neurogenic fever, and paroxysmal sympathetic hyperactivity (PSH) are important complications to recognize.9
Post-traumatic cerebral vasospasm is a dangerous complication of brain injury, as it can lead to delayed cerebral ischemia. Vasospasm occurs in one-third of those with TBI and can significantly affect outcome. It commonly occurs between days 2 and 15 following injury. Fifty percent of the patients suffering from vasospasm also suffer cerebral hypoperfusion. The incidence of radiographic vasospasm correlates with severity of injury. It can be assessed with transcranial Doppler ultrasonography and digital subtraction angiography. Patients suffering from cerebral vasospasm warrant prompt evaluation by a neurointensivist.
Neurogenic fever is a sequela described in up to 37% of patients who survive TBI. It has been shown to be a result of damage to the hypothalamus and a diagnosis of exclusion characterized by relative bradycardia, absence of perspiration, and long-standing hyperthermia (absence of diurnal variation). Treatment of neurogenic fever includes external cooling agents and medications, including propranolol, amantadine, and bromocriptine.10 Neurogenic fever has been independently linked to TBI affecting the frontal lobe.10
PSH is also common following TBI and has been reported in up to 33% of patients suffering from TBI. It is characterized by tachycardia, fever, hypertension, tachypnea, pupillary dilation, and extensor posturing. The condition has also been described as paroxysmal autonomic instability with dystonia (PAID), a term usually reserved for patients suffering from a severe TBI. Patients should be managed symptomatically. Transfer to an intensive care unit is seldom warranted, unless there is the presence of a dangerously elevated blood pressure or heart rate.
While differences in incidence of any particular complication following traumatic brain injuries are often negligible, this is not always the case. When compared to closed brain injury patients, those suffering from a penetrating injury are 2.62 times more likely to have a lower Glasgow Coma Score.1 These patients are also at a greater risk of post-traumatic seizures and epilepsy. In fact, survivors of military penetrating head injury suffer by far the highest incidence of post-traumatic epilepsy (PTE), ranging from 32% to 55%.11 The types of materials penetrating the brain have also been shown to have an effect on PTE. For example, copper has been linked to a greater risk for developing epilepsy after penetrating brain injury.12
Penetrating brain injury can be divided into prognostic strata. Worse prognosis is associated with age greater than 50 years old, perforating injury (an injury with an entry and exit wound), low GCS score (Table 20–3), presence of respiratory distress, elevated intracranial pressure, and CT findings of bilateral or transventricular penetrating brain injury.13
Post-traumatic stress disorder (PTSD) has been linked to penetrating brain injury. Other factors linked to PTSD include increased oxidative stress, glutamate release, and chronic inflammation. It has been suggested that increasing expression of antioxidant enzymes and dietary antioxidant chemicals may be a way of reducing PTSD in this population.14
Trauma as a whole is often seen as a condition of the poor and medically underserved. As noted previously, patients who experience a penetrating brain injury are more likely to be nonwhite and less educated. These factors are not only important for the epidemiology of the condition, but have also been linked to management. In 2011, Hefferman et al evaluated the impact of socioethnic factors following traumatic brain injury.15 Higher income was linked to fewer leaves from hospital against medical advice, while having private insurance was linked to longer length of stay at the hospital. Patients who had private insurance were also noted to have decreased mortality after TBI. Non-Caucasian and uninsured patients had a lower likelihood of entering an acute inpatient rehabilitation center for their TBI. Physicians must be ever aware of these health care disparities in order to provide the best care possible for all of their patients.
Rehospitalization due to seizures in the penetrating brain injury population is nearly three times higher than in the nonpenetrating brain injury population. Cicatrices, areas of reactive gliosis in the cortex that are a pathological feature of penetrating brain injury, have been strongly linked to epilepsy and are thought to be strong epileptogenic foci. However, the etiology of injury is not usually taken into consideration when discussing post-traumatic seizure prophylaxis. In the absence of seizures, standard seizure prophylaxis for any person with TBI lasts for 7 days after injury. Given that there is a higher incidence of seizures in the penetrating brain injury population, it should be considered that these patients could require extended periods of seizure prophylaxis; however, this has not yet been validated.
In a rat model of penetrating brain injury, Gajavelli et al observed that oxygen consumption and glucose uptake were greatly reduced at the injury core.16 It is proposed that similar to ischemic stroke models, there exists a penumbra surrounding the injury core characterized by viable neurons that are at risk of neurodegeneration. This penumbra is characterized by decreased level of neurodegeneration. The presence of viable neurons in the penumbra could theoretically allow salvage treatments such as glucose and lactate supplementation. Other proposed treatment options targeting the brain injury penumbra include hyperbaric oxygen and hypothermia. Hyperbaric oxygen is thought to have the potential to improve oxygen supply to the injured brain and reduce the swelling associated with low oxygen levels. However, rodent models have suggested that hyperbaric oxygen supplementation has not been beneficial for treatment of penetrating brain injury.
Focal injury occurs at a specific site of the brain, typically after direct impact of the head with an object. Collision forces acting on the skull cause compression of the underlying tissue at the site of impact (coup) or of tissue opposite the site of impact (contre-coup). Additional examples include cerebral contusions; cerebral lacerations; and epidural, subdural, intracerebral, and intraventricular hemorrhages.
In a survey of 90,250 hospitalized patients with brain injury, 30.6% of patients had traumatic intracranial hemorrhage.17 Types of hemorrhage included subarachnoid (47.9%), subdural (40.6%), epidural (17.5%), intracerebral (14.0%), and intraventricular (4.3%). Focal injuries usually occur at the anterior and inferior portions of the frontal and temporal lobes due to a coup-contre-coup mechanism of injury.
As described in the penetrating brain injury section, focal injury consists of primary (phase 1) and secondary injury (phases 2 and 3). Cerebral contusions are typical pathological changes resulting from hemorrhagic lesions within the gray matter or at the gray–white matter interface.18 Following focal injury, secondary injury consists of a robust inflammatory response involving the activation of glia, neurons, and cerebral accumulation of blood leukocytes.19 Excessive glutamate levels characterize secondary injury. In areas of focal brain injury, a fiftyfold increase in extracellular glutamate has been identified.20
Mitochondrial damage also plays an important factor in brain injury. The severity of mitochondrial impairment assessed using high-resolution proton magnetic resonance spectroscopy has a positive correlation with worse outcome.21 After brain injury, caspase and calpain proteins play an important part in cellular apoptosis and necrosis, respectively. A calpain inhibitor administered to rats following brain injury has been shown to attenuate motor and cognitive deficits compared to control animals.22
Focal and diffuse traumatic brain injuries (detailed later) can lead to similar clinical pictures even though they may have different mechanisms of action. If both coexist, clinical findings produced by focal injury can be masked by diffuse injury. Likewise, in mild and some moderate diffuse injury, large focal areas of injury will dominate a patient’s symptoms. In cases of severe diffuse brain injury, focal injury plays a lesser role in the patient’s clinical presentation.
Location of injury can play an important role in signs, symptoms, and presentation. For example, prefrontal/frontal injury can result in alterations in impulsivity, attention, affect, memory, and higher-level cognition. Injury at anterior and inferior temporal regions can lead to altered behavior and affect. Larger areas of injury extending into medial temporal areas can produce memory impairment, such as amnesia. Injuries extending to visual and auditory areas produce visual agnosia and aphasia, respectively. These patients may also suffer from confusion and decreased arousal.
Noncontrast brain CT is the initial diagnostic tool of choice for all patients presenting with moderate and severe brain injury. This imaging modality is fast, relatively inexpensive, and can help guide initial surgical treatment if necessary. MRI is better used for occult lesions and patient follow-up. However, it is recommended in the acute setting when the patient’s symptoms are out of proportion to the initial findings on a brain CT scan.
Different forms of hemorrhagic injury exist, and each has a unique appearance on imaging. Intra-axial hemorrhagic contusions have a hypodense rim that represents edema, involve gray matter, and usually are localized to the anterior and basal aspects of the frontal, temporal, and occipital lobes. Epidural hematomas can cross the midline but not sutures. They have a biconcave appearance between the brain and skull (Fig. 20–1). Subdural hematomas are confined to dural reflections and will not cross the midline. They can, however, cross sutures. They will appear as a crescent-shaped, hyperdense collection(s) on noncontrast CT (Fig. 20–2). Subarachnoid hemorrhage presents as hyperdense blood within the brain sulci or basal cisterns. Brain CT is more sensitive for detection of acute subarachnoid hemorrhage (Fig. 20–3). Intraventricular hemorrhage may occur within any ventricle but most commonly occurs in the lateral ventricle(s) after trauma (Fig. 20–4).
Localizing areas of focal injury can guide the patient’s rehabilitation. For example, patients with frontal contusions most often suffer from the aptly named frontal lobe syndrome. Understanding that these patients can be impulsive, for example, can guide the rehabilitation team’s plan. Furthermore, the same can be said about choosing certain medications for treatment of symptoms associated with TBI. For example, should a patient presenting with inattention have a TBI affecting the locus ceruleus-noradrenergic system, said patient may benefit from medication to increase levels of norepinephrine.
Epidural and subdural hematoma should be monitored as to size and compression of adjacent areas. If a hematoma is causing significant mass effect/shift or neurologic deterioration, it warrants prompt neurosurgical evaluation and evacuation. Intracerebral hemorrhage or cerebral contusions warrant close evaluation of intracerebral pressure and neurologic status due to the high risk of expansion. Contusions in temporal lobes are adjacent to the brainstem, and swelling or mass effect in these areas can lead to uncal herniation, a life-threatening complication that requires close monitoring and urgent neurosurgical management if present.
Intraventricular hemorrhage, as well as other types of closed brain injuries, may lead to hydrocephalus by obstruction of cerebrospinal fluid (CSF) flow. This can lead to mass effect and damage of brain matter. Hydrocephalus is best visualized with CT and should be evaluated by neurosurgery for consideration of ventricular drainage or shunting.
Other treatment considerations for any TBI include the management of increased tone and spasticity, pain (nociceptive and neuropathic), and optimization of basic needs (bowel, bladder, sleep, etc.). While specific treatments of these conditions is outside the scope of this chapter, it is important that they be considered in the treatment regimen of any person with TBI.
Complications (neurogenic fever, vasospasm, etc.) are discussed in the penetrating brain injury section and also apply to closed brain injuries.
The concept of initiating prophylactic management for the prevention of venous thromboembolism (VTE) in patients who have suffered from TBI is often contested. In a population of individuals who were status-post hemorrhagic head trauma without exposure to prophylactic measures, the occurrence of VTE was 54%. Some physicians may be hesitant to employ pharmacological prophylaxis in this population due to the perceived risk of increased intracerebral bleeding. On the contrary, both chemical and pharmacological interventions have been established as safe and viable options for VTE prophylaxis. In a systematic review by Shen et al, pharmacological thromboprophylaxis was shown to be a safe and effective means of reducing the incidence of VTE in the traumatic brain injured population.23 In general, TBI can be treated with chemical prophylaxis between 24 and 72 hours after injury. This depends on the complexity of the injury, as detailed in Fig. 20–5.
In the aforementioned study, there was no superiority between pharmacological interventions. In light of this evidence, physicians treating patients with closed brain injury should strongly consider using pharmacological prophylaxis for VTE within the first 72 hours following injury.
Historically, the concept of diffuse axonal injury (DAI) was first described by S. J. Strich as diffuse degeneration of white brain matter in his 1956 publication, “Diffuse Degeneration of the Cerebral White Matter in Severe Dementia Following Head Injury.”24 In the 1980s, the term diffuse axonal injury was first introduced and described by Adams et al as a clinicopathological entity.25 Since then, the basic concept underlying DAI has evolved.
DAI is caused by white matter axonal injury, which is secondary to the shear and strain of mechanical trauma. The condition is characterized by the progression from disrupted axonal transport, to axonal swelling and secondary disconnection, and finally to Wallerian degeneration. Clinically, DAI is characterized by unconsciousness immediately following head impact and can progress to brain failure, vegetative state, and death.
Pathologically, DAI is defined by the presence of lesions representing damaged axonal fibers throughout white matter tracts—specifically within the corpus callosum, cerebral hemispheres, and brainstem.
DAI is characterized by multiple small lesions. These include hemorrhagic microbleeds (also referred to as traumatic microbleeds [TMBs] and small nonhemorrhagic lesions found in white matter regions. Although diffuse implies widespread, it is important to note that DAIs are lesions localized to multiple common areas within white matter tracts. Based upon the path and anatomic depth of such lesions, three grades of DAI exist and are listed here in the order of increasing severity:
Grade I: Typically located in the cortical-subcortical junction of cerebral hemispheres, particularly in the frontal and parietal parasagittal white matter; anterior temporal white matter is another well-known location of axonal injury.
Grade 1: SWI image-axonal injury on SWI: Lesions typically located along the parasagittal frontoparietal white matter in the form of “rosary beads” (arrow).
Grade II: Additional lesions in the corpus callosum; often involve the posterior body and splenium; lesions tend to be located to one side of the midline. Associated lesions in septum pellucidum and fornices may be seen.
Grade 2: SWI image – Hemorrhagic axonal injury in the right side splenium. Also, note the smaller lesion near right frontal horn (arrows).
Grade III: Lesions present in the brainstem and typically affect the dorsolateral portion of midbrain and rostral pons, including the superior cerebellar peduncles.
Grade 3 – SWI image-several foci of microhemorrhages from DAI in the dorsolateral aspect of caudal midbrain (arrow).
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