Surgical Management of Severe Closed Head Injury in Adults

Acknowledgments

We want to express our appreciation to the medical illustrators Matthew Holt and Scott Barrows for their superb artistic work in the elaboration of Figs. 121.1 , 121.2 and 121.7 , as well as to Pere Lluis Leon, the professional scientific illustrator who elaborated Figs. 121.4 and 121.11 . We are also grateful to George Hamilton and Kristine Osmond for their critical review of the language and style of the manuscript.

“And if incision of the temple is made on the left, spasm seizes the parts on the right, while if the incision is on the right, spasm seizes the parts on the left.”

Hippocrates
On Wounds in the Head,
in Hippocrates, translation by
E. T. Withington (1927), Vol. 3, 33

Supplementary text and figures about “Neuroscience of TBI” in addition to the whole reference list are available on Expert Consult.

Head trauma is a general term that indicates any alteration of the brain, skull, and/or scalp related to a blow to the head. The term traumatic brain injury (TBI) specifically refers to damage to the brain resulting from external mechanical forces. Head trauma accounts for a significant proportion of admissions in most neurosurgical departments. The basic principles of surgical treatment of traumatic brain injuries have not changed much in the last decades and consist of the use of large craniotomies and the prompt evacuation of hemorrhagic mass lesions. The results of extensive laboratory research carried out in recent decades in search of new pharmacologic treatments for TBI have been particularly frustrating, as the encouraging outcomes achieved in animal models have not translated into a single successful clinical trial or effective therapy. Head trauma remains a major neurologic disorder for which there is no effective pharmacologic treatment.

TBI is a complex pathologic condition due not only to the great heterogeneity of lesions present in each patient but also to the dynamic progression of damage associated with each lesion. Severe TBI represents a serious medical and scientific challenge that includes a wide range of brain lesions with separate pathophysiologic mechanisms that may require different therapeutic approaches. One of the central concepts that emerged from research is that all cerebral damage from TBI does not occur at the moment of the impact but rather evolves over the ensuing hours and days. Focused protocol-driven management, including rapid resuscitation and early intubation in the field, direct transport to a major trauma center, improved critical care management in the hospital with intracranial pressure (ICP) monitoring, and immediate evacuation of mass lesions has cut mortality in severe TBI from 50% in the 1970s to 15-25% in the 2000s. However, this tremendous advance seems to be at a standstill, as the enormous complexity of the cellular and molecular mechanisms involved in the progression of traumatic brain damage seem to represent, for the time being, an insurmountable obstacle for the development of target-driven therapies.

The surgical management of TBI has long been based on anecdotal clinical practice. The new paradigm of evidence-based medicine has broadened to the establishment of scientific surgical and medical guidelines, which should help neurosurgeons make better decisions using a strong scientific background, in addition to their personal experience. The most widely used method for the assessment and stratification of TBI severity is the Glasgow Coma Scale (GCS), which categorizes patients according to the degree of impairment of consciousness, estimated from their verbal, motor, and eye-opening responses to external stimuli. Following this classification system, a severe head injury is defined by an initial post-resuscitation GCS score between 3 and 8 points or by deterioration to a GCS score of 8 or fewer points after injury.

TBI treatment is a team effort integrated by surgeons and clinicians, but the role played by neurosurgeons remains critical, especially regarding therapeutic decisions that are made to reduce the progression of secondary brain damage. Coping with severe TBI patients cannot be done in a “cookbook” fashion. Rather, individual patient care must be based on the best available evidence, ideally assessed by an experienced team of neurosurgeons and neurotrauma practitioners.

In the online version of this chapter, a section focusing on the neuroscience of TBI is provided. The expanding advance of neurosciences in the last decades has produced outstanding insights into the intrinsic, dynamic mechanisms of cell damage set in motion by head trauma. Succinct knowledge of these basic mechanisms can help neurosurgeons involved in the care of severely head-injured patients, as it represents the keystone for identifying potential future therapeutic targets for TBI.

Epidemiology

TBI constitutes a major cause of death and severe disability in young and adult people in western countries. In 2010, the Centers for Disease Control and Prevention estimated that TBIs accounted for approximately 2.5 million emergency department visits, hospitalizations, and deaths in the United States. Deaths occurred in about 2% of them (50,000 cases). Overall, TBI contributes to about 30% to 40% of all deaths from acute injuries in the United States, and many survivors face neurological, neuropsychiatric, and cognitive sequelae the rest of their lives. ^, TBI is the leading cause of permanent neurologic sequelae in children and young adults, with about 3.2 million to 5.3 million persons in the United States living with disabilities related to TBI. ^, Overall, it is estimated that around 100,000 patients per year are operated on for a post-traumatic intracranial hematoma (ICH) in the United States.

A steep increase in the rate of head injuries involving the elderly population has been observed in the last two decades. In the United States alone, the rate of TBI-related hospital admissions for elderly people has risen by more than 50% from 2001 to 2010, whereas this rate has remained stable or declined for those between 15 and 44 years of age. Elderly patients typically sustain injuries from low-impact falls, and their clinical course is complicated by multiple comorbidities. ^, The clinical profile of this age group is quite different from that observed among young adults after high-velocity traffic injuries. Consequently, management strategies should be individualized according to the specific type of TBI, age, and comorbidities.

Classification Schemes for Traumatic Brain Injury

TBI heterogeneity is considered one of the most significant barriers to the development of effective therapeutic interventions. ^, With the aim of implementing a more accurate TBI classification system that takes into account the heterogeneity and complexity of the injury and may eventually allow the improvement of patients’ outcomes, a multidisciplinary, international expert panel has recently developed a database including clinical, imaging, proteomic, genomic, and outcome biomarkers, known as the TBI Common Data Elements. The multicenter prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study has validated the feasibility of collecting these data. To date, TRACK-TBI investigators have published several articles, most of them related to potential biomarkers that could be used as diagnostic tools or predictors of TBI outcome.

Traumatic Brain Injury Classification Systems for Targeted Therapies

Different classification systems for TBI have been used depending on the categories of data chosen for clinical assessment and/or research. The major limitation of these schemes is that the optimal time to classify patients is unknown and depends on the purpose of classification. Furthermore, formal training is required to ensure consistent and standardized use of the scales. Head injuries have more often been classified according to the severity of the clinical symptoms. However, pathoanatomic classifications may be more useful because they provide an accurate description of the lesions that should be treated. In general, the degree of neurologic derangement is the most important factor to take into account for triage, whereas the type of injury is of predominant importance when classifying patients regarding the selection of treatment. Finally, outcome-based systems of classification have been developed to focus on patient’s functional capacity and severity of permanent disabilities.

Classification Schemes According to Injury Severity

The GCS was originally designed by neurosurgery professors Graham Teasdale and Bryan Jennet in the early 1970s to describe unconsciousness after brain injury, and created a severity scale that continues to be the most commonly used scale for TBI patients ( Table 121.1A ). This scale includes assessment of eye opening, best verbal response, and best motor response. The total score, ranging from 3 to 15 points, should be ascertained after resuscitation, because the neurologic examination can be markedly altered by hypotension or hypoxia. TBI patients are typically divided into three subgroups based on the total score: severe TBI (GCS score 3 to 8 points), moderate TBI (GCS score 9 to 12 points), and mild TBI (GCS score 13 to 15 points).

Table 121.1

Classification Schemes for Traumatic Brain Injury

Table 121.1AClassification by Injury Severity (The Glasgow Coma Scale5)

Score	Eye Opening	Best Verbal Response	Best Motor Response (Arms)
6	–	–	Obeys commands
5	–	Oriented	Localizes to pain
4	Spontaneous	Confused	Withdraws limb to pain
3	To speech	Single words	Flexes limp in response to pain (decorticates)
2	To pain	Incomprehensive	Extends limb in response to pain (decerebrates)
1	No response	No response	No response

The scores in eye, verbal, and motor responses are summed to yield the overall value.

GCS 13-15: mild head trauma; GCS 9-12: moderate head trauma; GCS 3-8: severe head trauma.

Most severely head-injured patients fall into a coma, a neurologic state defined by the International Coma Data Bank as the inability to obey commands, utter words, or open eyes. The GCS is an easy method for bedside assessment of the degree of impairment of consciousness with a high inter-observer reliability and good outcome prediction. The main disadvantages of the GCS system are that multiple combinations of eye, motor, and verbal scores can equal the same total score, and that pupillary reaction and lateralization of the exam are not included. Assessment of pupillary diameter and reactivity continues to be of paramount importance. The reliability of the GCS should be questioned in the setting of sedative and paralytics use. The optimal timing of measurement is unclear, with a change in the score being more relevant than a single measure.

The management of patients suffering from an acute brain injury is mainly based on the computed tomography (CT) findings rather than on the clinical monitoring of conscious level with the GCS score. A majority of clinicians favor adopting an anticipatory approach in the setting of TBI that aims to identify and deal with sources of potential worsening rather than to react to adverse developments. For example, space-occupying hematomas are preferably operated on before clinical signs of brainstem herniation occur. This operational approach has minimized mortality and morbidity in patients with ICHs.

Classification Schemes Based on Pathoanatomic Findings

TBI classification schemes based on pathoanatomic findings describe the location and type of abnormalities to be targeted by treatment. The majority of severely head-injured patients have more than one type of injury when classified in this way, such as scalp lacerations, skull fractures, ICHs, traumatic subarachnoid hemorrhage (SAH), intraventricular hemorrhage, cerebral contusions, and diffuse patterns of injury such as diffuse axonal injury (DAI), diffuse brain swelling, or brain ischemia. The use of combined clinical and neuroradiologic information including the GCS score, the length of patient’s coma, and the type of lesion shown by CT (focal or diffuse) has allowed a better prediction of patient’s outcome. For example, several studies have observed that subdural hematomas (SDHs), multiple brain contusions, and diffuse injuries associated with a coma for more than 24 hours are associated with the highest mortality. ^,

In 1991, Marshall et al. described a CT classification system based on information gathered from severe TBI patients in the Traumatic Coma Data Bank (TCDB). ^, This scheme is based on the appearance of the perimesencephalic cisterns, the presence of midline shift, and the presence of focal masses ( Table 121.1B ). This pathoanatomic scheme has proven to be the most successful in predicting the risk of increased ICP as well as the outcome of a patient after a TBI. Diffuse injury type IV is the one associated with the highest mortality.

Table 121.1B

Classification by Pathoanatomic Findings (Marshall’s Computed Tomography Classification )

Type	Radiologic Findings on CT
Diffuse Type I (no visible pathology)	No visible intracranial pathology seen on CT scan
Diffuse Type II (no swelling and no shift)	Cisterns are present with midline shift <5 mm and/or lesion densities present. No high- or mixed-density lesion >25 mL, may include bone fragments and foreign bodies.
Diffuse Type III (swelling)	Cisterns compressed or absent with midline shift 0–5 mm. No high-or mixed-density lesion >25 mL
Diffuse Type IV (shift)	Midline shift >5mm. No high- or mixed-density lesion >25 mL
Type V (evacuated)	Any lesion surgically evacuated
Type VI (non evacuated)	High- or mixed-density lesion >25 mL, not surgically evacuated

CT , Computed tomography.

Classification Schemes by Biomechanical Mechanism of Injury

Head injuries can be classified according to whether the head is struck or strikes an object (contact or impact loading) and/or the brain moves within the skull (noncontact or “inertial” loading). The magnitude and direction of the combined loading forces may predict the type and severity of injury. There is considerable correlation between physical mechanism of injury and pathoanatomic injury type. For instance, most focal injuries, such as skull fractures, brain contusions, and epidural hematomas (EDHs), result from impact loading, whereas inertial loading generally causes more diffuse injuries, such as concussion, SDHs, and DAI. However, in clinical practice, mechanistic classification is difficult to apply because of the uncertainty about the loading conditions involved in the TBI.

Classification Schemes by Pathophysiology

Pathophysiologic classification schemes in TBI take into consideration biochemical, metabolic, neurophysiologic, and/or genetic dynamic processes set in motion by the injury. A simple and widely used physiopathologic scheme introduced by Adams et al. differentiates between the unavoidable, immediate-impact parenchymal damage of primary injury, and the potentially avoidable damage from secondary injury. Severe head injury patients often have extracranial injuries (e.g., fractures and chest and abdominal trauma) and massive bleeding that can cause hypoxia or arterial hypotension. In addition to secondary ischemic injury, secondary damage can be caused by neurotransmitter dysfunction, cellular and extracellular edema, blood-brain barrier (BBB) disruption, mitochondrial damage, genetic alterations such as apoptotic induction, and so on. The potential therapeutic window for blocking the molecular and cellular pathways involved in secondary insults may be minutes, hours, or days following the impact, which has aroused great expectations. Unfortunately, the enormous body of experimental research carried out so far has not yet been translated into any specific treatment in the clinical setting.

Classification Schemes by Prognostic Modeling

Outcome after TBI depends on multiple factors including the brain damage, extracranial injuries, comorbid conditions, preinjury status, social factors, and patient age. Traditionally, the Glasgow outcome scale (GOS) has been used to categorize the long-term prognosis of patients following TBI ( Table 121.1C ). Most TBI patients fall into the extremes of the scale, good recovery or death, and the scheme has undergone several revisions and was extended to an 8-point scale (extended GOS) to address some of these limitations. Both the GOS and the extended GOS have been extensively used and have been shown to have validity and reliability in the measurement of outcome by trained staff. Both scales are also correlated with other measurements of disability, mental status, and neurobehavioral functioning.

Table 121.1C

Classification by Prognostic Modeling (Glasgow Outcome Scale)

Score	Features
1	Dead
2	Vegetative state (unable to interact with environment, unresponsive)
3	Severely disabled (able to follow commands, unable to live independently)
4	Moderately disabled (able to live independently, unable to return to work/social activities)
5	Good recovery (the patient has resumed most normal activities)

Biomechanics of Traumatic Brain Injury

TBI is generally the result of inertial linear and rotational acceleration/deceleration (A/D) forces acting on brain tissue. Nervous tissue strains induced by both linear and rotational forces create spatiotemporal deformation gradients, poorly tolerated by a viscoelastic organ with little internal structural support such as the brain. Gray matter closest to the surface of the brain is most susceptible to linear A/D forces. In contrast, the deeper cerebral white matter axons, including the axonal tracts within the brainstem, are more vulnerable to rotational A/D forces. The shear strains caused by rotational A/D forces (also known as impulsive loadings) were first observed in the early 1940s on physical gelatin models resembling grossly the brain’s physical properties ( Fig. 121.1 ). Later on, exhaustive postmortem neuropathologic studies on the brains of patients who died from lethal road accidents showed that the predominant microscopic finding was a diffuse degeneration of white matter characterized by the development of axoplasmic “retraction balls” at the sites of axonal discontinuity, without obvious damage to the cortex. Retraction balls at the end of injured axons were originally described by the Spanish histologist and Nobel Prize winner Santiago Ramón y Cajal (1852–1934). ^, This type of axonal lesion was termed “shearing injury” by Strich, because he thought that the shearing of nerve fibers at the moment of injury represented the landmark of traumatic damage to white matter. Clinico-pathologic studies undertaken by Adams et al. endorsed Strich’s views, and Jennet and Plum considered this to be the most common cause of the vegetative state observed in severely head-injured patients. , ^,

Figure 121.1, Biomechanics of traumatic head injury. Classic model of spatiotemporal deformation gradient caused by acceleration/deceleration forces. Impact loadings inflicted on the freely moving head initiate a deformation wave that travels in the viscoelastic brain tissue, creating a spatiotemporal gradient. 17 , 21 The major structural lesion is characterized by a stretching injury of the axolemma of scattered neurons, which cause development of multifocal swellings (A) and blocking of normal axonal transport (B), but the maximal degree of deformation may cause direct tearing (C) or breaking (D) of axons.

Diffuse brain injury usually results from inertial loadings caused by rapid rotational motions of the brain following unrestricted head movement at the instant of injury. Rapid A/D head movements deform white matter, inducing dynamic shear and tensile and compressive strains within tissues (see Fig. 121.1 ). In 1974, Ommaya and Gennarelli proposed a “centripetal model” of severity of brain damage caused by head injuries, based on experimental studies performed in primates. ^, These experiments, in which the head of an animal was exposed to A/D forces using accelerator devices, showed that nonimpact A/D caused concussion and axonal injury only when the moving head was allowed to rotate, while linear accelerations induced gross structural damage but not DAI. ^, According to the Ommaya-Gennarelli model, the mechanical strain injury operates in the brain tissue in a “centripetal sequence,” in which the higher the magnitude of the injuring force, the deeper the structural damage. The sequence of damage begins at the surface of the brain and affects progressively deeper structures as the A/D forces increase in intensity. The centripetal model challenged the prevalent view that the main mechanism producing traumatic unconsciousness after TBI was an isolated brainstem injury. The centripetal model introduced two critical predictions: (1) when the degree of trauma is sufficient to cause loss of consciousness (LOC), cortical and subcortical structures are primarily affected and show more severe damage than that found in the rostral brainstem; and (2) damage to the rostral brainstem does not occur without more severe damage to cortical and subcortical structures. The primary brainstem damage theory was popular in the 1950s and 1960s, when the ascending arousal system (AAS) was described by Moruzzi and Magoun. Although early studies suggested that the primary site of brain injury in patients presenting with transient LOC and post-traumatic cognitive deficits was the brainstem, overwhelming neuropathologic evidence showed that most mild and moderate TBI caused damage to widespread areas of the cortex and the subcortical white matter. ^, Recent magnetic resonance imaging (MRI) studies, in which the assessment of DAI was performed during the first month after injury, confirmed the Ommaya-Gennarelli model. Nevertheless, the most recent biomechanical studies on TBI consider that besides the intracerebral pressure waves caused by linear and rotational A/D loadings, the head motions occurring at the moment of injury result also in intracranial brain deformations, which are thought to be a primary cause of the post-traumatic brain lesions. The stereotactic theory considers brain tissue to be a spherical, deformable structure composed of concentric planes with the same density in which skull vibrations generate secondary pressure waves that propagate as a spherical wave front. The spherical nature of this wave front is able to focus its energy on deeper cerebral structures without an associated injury at the brain surface (see Fig. 121.1 ).

Neuropathology of Traumatic Brain Injury

In 1990, Adams summarized the neuropathologic postmortem findings obtained from one of the largest series of TBI patients ( n = 434), the Glasgow database. One-third of these patients had “talked” at some time after the injury. The first major conclusion from this work was that severe brain damage can be caused without anything striking the head or the head striking anything. The second conclusion was that DAI represents the most important factor influencing the outcome in anyone who sustains a non-missile head injury, followed by secondary brain ischemia, which represented the second prognostic factor of importance after TBI.

According to the pathologic classification introduced by Gennarelli in 1987, two major types of post-traumatic lesions could be differentiated in Adam’s series: focal lesions, including cerebral contusions and ICHs; and diffuse injuries, which cannot be macroscopically identified, including DAI, diffuse brain swelling, secondary hypoxic/ischemic brain damage, and diffuse vascular injury ( Figs. 121.2 and 121.3 ). Focal brain injuries can be produced when the stationary skull is struck by a moving object with relatively small mass, such as a stick or baseball bat. Focal brain injuries are characterized by a central area of structural disruption, surrounded by an area of primary traumatic damage without destruction of brain tissue, and finally enclosed by a peripheral tertiary zone of potential delayed insult associated with ischemia and edema.

Figure 121.2, Types of intracranial posttraumatic lesions. Besides DAI, the four major intracranial lesions are epidural hematomas (EDH) (A), acute subdural hematoma (SDH) (B), contusions and intracerebral hemorrhages (C), and diffuse brain swelling (D). The lower row depicts in detail the causal mechanism for each type of posttraumatic lesion. (A) An EDH is a clot between the inner surface of the skull and the stripped-off dura mater that generally has a biconvex morphology and usually results from injury to the middle meningeal artery. (B) An acute SDH is a clot between the inner surface of the dura mater and the pial surface of the brain that has a crescentic shape and usually results from torn bridging veins. (C) Contusions are bruises of brain tissue characterized by extravasation of blood from small vessels, ischemia, and necrosis of brain tissue. (D) Diffuse brain edema consists of the accumulation of water within the brain, generally inside the cells and specifically inside the end feet of astrocytes that surround capillaries.

Figure 121.3, Neuropathology of traumatic brain injury. (A) Basal view of an injured brain, showing large contusive foci involving both frontal and temporal poles (burst lobe lesions). (B) Coronal slice of the brain, showing macroscopic hemorrhagic lesions within the corpus callosum associated with DAI (Adams classification grade II). (C) Brainstem axial slice, showing hemorrhagic lesions in the dorsolateral quadrants of the mesencephalon associated with severe DAI (Adams classification grade III). (D) Posttraumatic axonal swellings revealed by APP immunostaining. (E) Detail of axonal retraction balls.

The importance of diffuse brain lesions caused by TBI was first emphasized by Symmonds as the cause of initial LOC and the frequent long continued disturbances of consciousness, often followed by residual symptoms in patients who were rendered unconscious at the moment of injury. Later experimental work by Denny-Brown and Russell and more recent work by Gennarelli et al. linked this type of damage to the prolonged unconsciousness occurring in almost half of severely head-injured patients in the absence of intracranial mass lesion. Diffuse injury is difficult to define in living patients, because much of it can only be recognized microscopically. Even in postmortem studies, it can hardly be recognized unless the brain is properly fixed prior to dissection. Nevertheless, this type of injury should be suspected in comatose patients without focal lesions.

Specific Features of Traumatic Brain Injury in Elderly People

TBI in older patients typically results from low-energy impacts such as ground-level falls, which associates a high proportion of SDHs but fewer contusions, EDHs, and axonal injury lesions in this age group. Age has been identified as an independent risk factor for poor outcome after TBI due to several factors. First, age-related comorbidities (e.g., diabetes, chronic cardiorespiratory disease, and renal dysfunction) favor hypoxia and hypotension and thus increase the severity of brain damage. In addition, many of the treatments used for chronic diseases—in particular, anticoagulant and antiplatelet drugs—increase the risk of hemorrhage or may worsen the evolution of intracerebral traumatic lesions. Finally, rehabilitation therapy is considered of limited value due to the diminished cerebral functions in many older patients. Nevertheless, a recent study including 4378 patients with TBI in the United Kingdom suggested that the increased mortality associated with cerebral contusion in the elderly might also be related to suboptimal care for older patients. On the other hand, ICP and CPP thresholds might be different compared to the young population because of age-related brain atrophy and loss of brain autoregulation due to chronic arterial hypertension. Lower ICP and higher CPP values might be particularly desirable in elderly patients with a history of arterial hypertension. The selection of appropriate surgical procedures may be more difficult in this age group, since the large body of evidence about outcomes in TBI accumulated over the past four decades is mostly derived from young patients. Further studies are needed to define the optimum management of elderly patients.

Traumatic Intracranial Hemorrhages

Post-traumatic intracranial hemorrhagic lesions represent the most common cause of clinical deterioration and death in head-injured patients with a lucid interval, especially those with skull fractures. If the lucid interval is longer than 24 hours, the hematoma is said to be “delayed.” It is very important to keep in mind that hemorrhagic traumatic lesions may appear or evolve within hours or days after the injury. Currently, patients are usually scanned within minutes of the trauma; thus, a routine second CT scan is recommended for all patients who remain comatose, because up to a third of cases may develop hemorrhagic lesions that may benefit from a surgical treatment. A new CT must be done in the case of any substantial clinical worsening or if patients sustain any unexplained ICP rise.

The three most important types of intracranial hemorrhagic lesions caused by TBIs are EDHs, acute SDHs, and intracerebral hemorrhages (ICHs) (see Fig. 121.2A–C ). EDHs corresponded to 8% of lesions observed in the Glasgow database, whereas “pure” SDHs were diagnosed in 13% and ICHs in 15% of lesions. A rate as high as 26% of patients had SDHs associated with ICHs in the context of a “burst lobe.” This term describes a massive lobar lesion showing the coexistence of cerebral contusions, blood in the subdural space, and a hematoma in the white matter deep to a contusion (see Fig. 121.3A ). Fatal head injuries associated with a cerebral hemorrhage affect predominantly older patients, a fact probably related to parenchymal atrophy and weaker structure of intracerebral small-caliber vessels in this age group. Other less frequent types of focal brain injuries are traumatic lesions of the corpus callosum, usually associated with DAI; tears in the brainstem, often associated with a ring fracture of the base of the skull; lesions of the hypothalamus and the pituitary stalk; and lesions of the cranial nerves, with loss of smell secondary to avulsion of the olfactory nerves. For a detailed description of ICHs, refer to the section on surgical treatment of TBI.

Cerebral Contusions: Major Gray Matter Focal Lesions After Traumatic Brain Injury

Brain contusions are hemorrhagic lesions characterized by the presence of blood intermixed with brain tissue, under the intact pia mater. Brain contusions and lacerations are considered primary TBI lesions that are observed at the poles and orbital surface of the frontal lobes in up to 80% of autopsy studies performed on patients dying after trauma (see Figs. 121.2C and 121.3A ). Hemorrhagic contusions constitute areas of irreversibly damaged brain tissue. They are harmful to the surrounding viable tissue due to the noxious effect of blood. Contusions are basically impact-related lesions occurring with short-duration and high-acceleration impacts. Both brain contusions and lacerations are always accompanied by a certain degree of edema and by SAH, while intraventricular hemorrhage accompanies DAI in most cases. Cerebral lacerations represent destructive post-traumatic lesions in which disruption of cerebral tissue inevitably occurs, usually involving both the cortex and subcortical tissues. Direct lacerations are caused by penetrating craniocerebral wounds, whereas indirect lacerations result from severe A/D shearing forces.

A comprehensive classification of brain contusions was provided in the studies by Lindenberg and Freytag in the 1950s and by Oprescu in the 1960s. Among them, contusions beneath skull fractures, coup contusions at the site of impacts (see Fig. 121.2C ), contrecoup contusions in regions distant to but not always opposite the impact site (see Fig. 121.3A ), herniation contusions, and finally, gliding contusions, which are bilateral, post-traumatic hemorrhages in the cortex and subcortical white matter of the superomedial parasagittal margins of the cerebral hemispheres. Gliding contusions are thought to be caused by rotational A/D forces and are usually associated with DAI and small post-traumatic hematomas in the basal ganglia.

The complex dynamic sequence of the damage in cerebral contusions is not well understood. Early studies by Scheinker suggested that the cerebral vessels are primarily injured by the TBI and that the parenchymatous tissue develops a progressive secondary damage. The classic study of Lindenberg and Freytag differentiated two components in cerebral contusions: (1) the central area (core), in which cells undergo necrosis as the primary consequence of mechanical vascular and parenchymal injury, and (2) the peripheral area (rim), in which cellular swelling is observed. In contusive areas, neuronal bodies show vacuolar degeneration with chromatolysis and their axons show a varicose degeneration, a type of lesion originally described by Ramón y Cajal in 1928 and later reported by Strich. ^, ^, Up to 14 days after TBI, axonal retraction balls generally develop, rapidly followed by microglial and astrocytic reaction. From then on, a progressive Wallerian degeneration of axons is clearly visualized.

A rapid, massive type of cerebral edema associated with contusions may develop progressively within 12 to 72 hours after trauma, causing a marked elevation in ICP and a shift of brain tissues, which may result in a delayed neurologic deterioration known as the “talk and deteriorate” syndrome. ^, In addition, a “benign” slow form of delayed pericontusional edema, which rarely causes ICP elevation, is typically seen on T2-weighted MRI in white matter several days after injury. Immunohistochemical and MRI studies have observed that this vasogenic edema does not develop in contusions until 48 hours after injury, predominantly in the white matter surrounding the lesion, suggesting that it is not due only to increased cerebrovascular permeability. Because in the central area of the contusion the cellular elements uniformly undergo mechanical disintegration and homogenization, this process can create a rapid increase in osmolality in the core of the contusion that attracts a large amount of water. Recent MRI–diffusion-weighted imaging (DWI) studies have observed that a large amount of edema fluid accumulates in the necrotic core of brain contusions up to 72 hours after trauma, resulting in rapid expansion of the extracellular space detected by an increased value of the apparent diffusion coefficient. ^, An increment of osmolality within the necrotic core of cerebral contusions due to the accumulation of metabolic intermediate osmoles (idiogenic osmoles) associated with the enzymatic digestion of proteins, lipids, and deoxyribonucleic acid might account for the hyperosmolar gradient created within contusions.

Surgical Treatment of Cerebral Contusions

Despite intensive medical therapy, the elevated ICP caused by early massive edema associated with post-traumatic cerebral contusions is often uncontrollable and fatal. An explanation for this therapeutic failure would be that extremely high osmolality values (greater than 380 mOsm) within brain contusions make these lesions resistant to hyperosmotic diuretic therapy. Consequently, surgical treatment may be the best option for the efficient control of ICP. Nevertheless, indications for surgical intervention for severe cerebral contusions remain controversial.

The effects of surgical excision of the necrotic brain tissue in patients with severe cerebral contusions has been investigated in the Japan Neurotrauma Data Bank, in which a total of 1002 severe TBI patients were included. From 182 patients presenting with severe cerebral contusions, 66% were treated conservatively, whereas 34% underwent surgery. In most surgical cases, excision of necrotic tissue and clots, in addition to decompressive craniectomy (DC), was performed. A poorer outcome was observed in the group treated conservatively 6 months after injury, which showed a doubling of the mortality rate (48% vs. 23%). These data support the usefulness of surgical treatment for cerebral contusions to prevent clinical deterioration and death, especially in patients with GCS scores of 9 points or better at the time of admission (patients who talk and deteriorate).

Diffuse Axonal Injury: Basic Concepts

The term DAI, also known as diffuse white matter shearing injury, was coined by Gennarelli et al. to describe the scattered injury of white matter fibers observed throughout the brains of animals and humans who suffered TBI. The fundamental microscopic, neuropathologic finding of DAI is the development of globular expansions at the proximal and distal stumps of severed axons known as axonal retraction balls, first described by Ramón y Cajal in 1911 after causing injury to the cerebral cortex with a knife. Nearly half a century later, Strich described the same neuropathologic finding in the brains of patients in a permanent vegetative state after TBI and stressed that the disruption of white matter fibers was caused by shearing forces (see Figs. 121.1 , and 121.3D and E ).

DAI was observed in 30% of the cases included in the Glasgow database, typically in cases of head injury involving a pure inertial A/D noncontact loading of the head. ^, ^, Nevertheless, some degree of DAI is likely to be present in all patients with severe head injuries and is almost universally present in fatal TBI. Axonal damage typically occurs when the head is subjected to shear-strain forces in less than 50 msec, as seen in automobile crashes, in which the brain tissue behaves as a stiff mass transmitting tensile elongation to axons that causes damage to their cytoskeleton. Patients who sustain severe DAI, particularly when axonal injury occurs in the brainstem, are unconscious from the moment of impact and do not experience a lucid interval, remaining unconscious, vegetative, or at least severely disabled until death. DAI has been observed in 80% of patients suffering from a vegetative state. In 1977, Adams et al. identified the classic pathologic triad of hemorrhagic lesions in white matter, corpus callosum, and rostral brainstem typically observed in the severest form of DAI. According to the severity of the axonal damage, he proposed a classification of DAI in three categories of severity (see Fig. 121.3B and C ; Table 121.2 ). In patients recovering from a coma, DAI contributes to the functional neurologic disturbances usually present, such as spasticity, intellectual decline, and unmodulated behavior patterns.

Table 121.2

Classification of Diffuse Axonal Injury

Grade	Neuropathologic Findings	Stage	MRI Findings
1	Microscopic axonal damage in the white matter of cerebral hemispheres, corpus callosum, brainstem and/or cerebellum without hemorrhagic or necrotic lesions in corpus callosum or superior cerebellar peduncles.	1	Traumatic lesions confined to the lobar white matter or cerebellum only.
2	Additional (to 1) microscopically or macroscopically hemorrhagic or necrotic lesions in the corpus callosum.	2	Traumatic lesions in the corpus callosum ± lesions in the lobar white matter.
3	Additional (to 1) microscopically or macroscopically hemorrhagic or necrotic lesions in the dorsolateral quadrants of the rostral brainstem.	3	Traumatic lesions in the brainstem (dorsolateral quadrant of the upper brainstem, superior cerebellar peduncles) ± lesions in the lobar white matter or corpus callosum.

MRI , Magnetic resonance imaging.

Diagnosis of Diffuse Axonal Injury

DAI is a predominant pathologic feature of fatal TBI. However, there are no validated methods for assessing white matter injury in the living human brain. Even the most sensitive modern MRI methods still underestimate the extent and severity of DAI following head trauma. ^, It is accepted today that patients in whom the CT scan discloses focal petechial hemorrhages represent only the severest forms of DAI and that MRI can show many more lesions than CT in a large number of these patients. Shearing injuries are displayed on MRI studies as multiple, small, ovoid lesions of 5 to 15 mm with their long axis paralleling the direction of the affected axons, most frequently found in the corpus callosum and in parasagittal regions of the brain (see Fig. 121.3B and C ; Table 121.2 ). ^, The definitive diagnosis of DAI can only be confirmed on postmortem studies using immunohistochemical methods such as antibodies against the beta-amyloid precursor protein (β-APP). β-APP is a protein normally transported along the axon that accumulates at the axonal beads after DAI, serving as an accurate marker for impaired axonal transport. ^, In TBI, β-APP accumulates before disruption of the axolemma and before axonal retraction balls appear, suggesting that axonal transport failure is an early event ( eFig 121.17A ). Using these immunohistochemical methods, DAI is detected in nearly 100% of moderately and severely head-injured patients.

Neuroradiologic Diagnostic Methods in Traumatic Brain Injury

Computed Tomography Scanning

Cranial noncontrast CT scanning is the neuroimaging modality of choice for evaluating head-injured patients to identify quickly the presence of life-threatening intracranial lesions. Three major findings should be evaluated on a head-injured patient’s CT: (1) the presence of ICHs, (2) the appearance of basal cisterns at the midbrain level, and (3) the presence of traumatic SAH.

The status of the basal cisterns is related to clinical outcome. Basal cisterns can be open (all limbs are open), partially closed (one or two limbs are obliterated), or completely closed (all limbs are obliterated). Compressed or absent basal cisterns indicate a threefold risk of raised ICP. Mortality is increased twofold in the presence of traumatic SAH, a sign that, when observed at the basal cisterns, carries a positive predictive value of unfavorable outcome of approximately 70%.

Approximately 10% of initial head CT scans in patients with severe TBI do not show abnormalities, and significant new lesions associated with increased ICP may develop in 40% of patients with an initially normal head CT scan. A CT scan should be repeated, especially if the first scan was obtained within a few hours of injury or if the patient has the potential of developing surgical lesions such as cerebral contusions, before clinical signs of neurologic deterioration are apparent. Based on a review of 154 consecutive patients with closed head injury requiring surgical intervention, McBride et al. recommended a repeat CT scan within 4 to 8 hours of the initial scan in all patients with an abnormal initial scan, given that nearly 50% of patients received surgical intervention based on the findings of the follow-up CT scan. Risk factors for developing delayed cerebral insults are the clinical severity of the head injury as defined by the initial GCS score, the need for cardiopulmonary resuscitation at the accident site, the presence of an acute SDH on the first CT scan, and the presence of coagulopathy on admission.

Magnetic Resonance Imaging

CT scanning continues to be the routine neuroimaging technique in the acute phase of TBI, but the importance of MRI is increasingly recognized. MRI is recommended in post-traumatic coma unexplained by CT scan, both for diagnosis and for prognosis. MRI is a better prognostic tool for TBI than CT because it can detect both hemorrhagic and non-hemorrhagic DAI in addition to brainstem lesions. Up to 85% of severely head-injured patients showing brainstem injury on MRI have an unfavorable outcome (death, vegetative state, or severe disability), compared to 55% of patients without brainstem lesions. Table 121.3 summarizes the most important characteristics and findings obtained with MRI sequences after TBI.

Table 121.3

Magnetic Resonance Imaging Techniques and Traumatic Axonal Injury ^, ^,

MR Techniques		Features
Conventional Imaging	T2-weighted	Limited in detecting periventricular/cortical lesions due to the presence of cerebrospinal fluid nearby
	Fluid attenuated inversion recovery (FLAIR)	Very sensitive to non-hemorrhagic lesions. It suppresses the signal produced by cerebrospinal fluid and detects a larger number of lesions (ischemic TAI = hypersignal)
	T2-weighted-gradient echo pulse sequence (GRE)	Very sensitive to paramagnetic blood breakdown products and thus to microhemorrhages (hemorrhagic TAI = hyposignal)
More sensitive sequences	Gradient echo pulse sequence-susceptibility weighted imaging (GRE-SWI)	Increases the ability of GRE images to detect hemorrhagic lesions
	Diffusion weighted imaging (DWI) Detects alterations since 3 h after injury.	Accurate method of examining non-hemorrhagic injuries but it is often not sufficiently accurate for the diagnosis of injuries to the corpus callosum and grey matter. Quantifies the overall restriction to water diffusion (apparent diffusion coefficient, ADC): there is an evolution from decreased ADC or restricted diffusion (cytotoxic edema) to an increased ADC or unrestricted diffusion (vasogenic edema) in TAI lesions.
	Diffusion tensor imaging (DTI) and DTI tractography	Quantifies the directionality of water diffusion in three-dimensional space providing in vivo information on the white matter integrity. Water diffuses more freely along the direction of the white matter fibers (fractional anisotropy, FA). This method can detect DAI in a highly sensitive way and allow estimation of the time elapsed from injury to examination. TAI is associated with FA reduction–that could be due to misalignment of fibers, edema, fiber disruption or axonal degeneration-.
	Proton magnetic resonance spectroscopy ( ¹ H-MRS) Detects alterations since the injury.	Assessment of neurochemical alterations in the following metabolites: Creatine (Cr), found in glia and neurons: its level is believed stable and serves as a point of reference to calculate metabolic ratios. N -acetyl-aspartate (NAA), an amino acid present in neurons: reflects status of neuronal tissue (↓ NAA/Cr ratio in TAI). Choline (Cho), component of cell membranes: reflects glial proliferation or membrane breakdown (↑ Cho/Cr ratio in TAI). Lactate, a marker of anaerobic metabolism and ischemia (↑ levels are seldom found in head-injured patients).

DAI , Diffuse axonal injury.

Advanced MRI Techniques

Newer MRI techniques better visualize axonal fiber damage and monitor dynamically the intracranial metabolic changes following head trauma. Diffusion-weighted MRI (MRI–DWI) allows the accurate discrimination of cytotoxic edema (characterized by decreased diffusivity) from vasogenic edema (increased diffusivity). In TBI, acutely increased diffusivity may indicate regions that undergo edema without cellular disruption, with the possibility that these areas will not progress to irreversible degeneration. In contrast, the regions showing acutely decreased diffusivity are more likely to have metabolic or other cellular disruption that will result in permanent degeneration. It is also important to note the timing of MRI because DAI regions may evolve from restricted diffusion (cytotoxic edema) to unrestricted diffusion (vasogenic edema).

The novel technique of diffusion tensor imaging (DTI) represents the most well-established newer imaging method to assess white matter structural integrity following TBI. DTI characterizes the directionality of water diffusion in a three-dimensional space, thus providing information on the physiologic status of particular axon bundles. Within the brain white matter, water diffuses faster along the predominant fiber direction, and more slowly in orthogonal directions. The resulting anisotropy (directional asymmetry) of water diffusion is higher in intact white matter compared to axonal injury. Thus, DTI evaluates the interruption of axolemmal transport and axonal leakage. This technique is capable of detecting abnormalities as early as 3 hours after injury. A recent retrospective study in severely head-injured patients found that DTI values in the acute/subacute stage of injury (<5 days after injury) provide significant prognostic information. Severe TBI patients (GCS <8) with good outcomes had DTI values similar to those of mild TBI patients; in contrast, poor clinical outcomes were associated with reductions in the axial diffusivity and fractional anisotropy in the corpus callosum.

Magnetic resonance spectroscopy (MRS), which is a method used to assess neurochemical alterations after brain injury, may also provide early prognostic information in TBI patients. Proton-MRS is the commonly used method in vivo, in which a reduction in the N -acetylaspartate/creatine ratio and an increase in the choline/creatine ratio are the most characteristic detectable findings after TBI. These changes reflect, respectively, the degree of neuronal loss/membrane breakdown and the degree of glial proliferation. Regions with reduced NAA/Cr ratios were confirmed as DAI at autopsy, supporting the hypothesis that NAA loss may, at least in part, reflect DAI. In addition, the MRS analysis of the biochemical profile in cerebral cortex and white matter of adult TBI patients studied 7 days after injury found that glutamate (Glu)/Glu+glutamine and Glu/choline ratios were significantly elevated in patients showing long-term outcomes of 4 or fewer points on the GOS 6 to 12 months after injury.

Non-Radiologic Diagnostic Methods in Traumatic Brain Injury

Serum Biomarkers of Diffuse Axonal Injury

Obvious limitations to performing MRI studies in the acute phase of severely head-injured patients have motivated the search for specific serum biomarkers for brain damage following head trauma. The proteins, S-100B and GFAP, predominantly localized in glial and Schwann cells, are the molecules most extensively studied thus far. All traumatic cerebral injuries have been shown to increase glial fibrillary acidic protein (GFAP) and S100B in serum, but focal injuries, such as cerebral contusions and SDHs, present higher levels as compared to diffuse injuries. Contusion volume has been directly correlated to serum levels of S100B. S100B levels may be used as a predictor of outcome in moderate-to-severe TBI patients, particularly when measured about 30 hours after head trauma. Nevertheless, S100B is not specific to brain and its diagnostic value is still unclear. To date, only the Scandinavian guidelines for TBI have incorporated it to reduce the number of unnecessary CT studies in mild TBI patients. On the premise that β-APP is the gold standard of DAI, some studies have proposed the detection of β-APP derivatives in identifying DAI. However, such studies are still scant and the clinical utility of these markers needs further investigation.

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