Epidemiology

TBI represents a serious health problem and constitutes a major cause of death and severe disability in young and adult people in Western countries. TBI afflicts 1.4 million people yearly in the United States, resulting in 50,000 deaths and 235,000 hospitalizations.⁶ TBI is the number one cause of coma and the leading cause of brain damage in children and young adults. The incidence (number of new cases) of head injury is approximately 300 per 100,000 people per year (0.3% of the population), with a mortality of 25 per 100,000 people in the United States. Approximately 500,000 head injuries requiring admission to a hospital occur annually in the United States, and 50,000 people with these injuries die before reaching a medical facility. Of the 450,000 initial survivors, 80% sustain minor injuries (GCS score 13-15 points), 10% have moderate injuries (GCS score 9-12 points), and 10% have severe brain injuries (GCS score 3-8 points).⁶ Around 100,000 patients per year may require surgical management of a post-traumatic intracranial hematoma in the United States alone.⁴ Roughly 50,000 head-injured patients per year will have some form of permanent disability.⁷

Classification Schemes for TBI

The heterogeneity of TBI is considered one of the most significant barriers to finding effective therapeutic interventions. In addition, the lack of a valid classification system for TBI that is able to identify subgroups of patients who may survive with a reasonable neurologic outcome and thus may benefit from specific therapies contributes to this therapeutic failure. A great heterogeneity of pathoanatomic lesions can be observed in neuroradiologic studies of patients classified under the same “severe TBI” category; thus, it is difficult to conceive a general therapy able to target such variability of traumatic lesions.⁸ To review the most common types and patterns of injury associated with TBI and develop a classification scheme that would cluster TBI patients into groups based on their major types of injury, the National Institute of Neurological Disorders and Stroke sponsored a workshop on classification of TBI for targeted therapies in October 2007.² On the premise that TBIs with similar pathoanatomic features are likely to share common physiopathologic mechanisms, a major conclusion from the workshop was that a new, multidimensional classification system for TBI should be developed and used in future TBI trials.

Biomechanics of TBI

TBI is generally the result not of a direct impact to the skull but of inertial linear and rotational acceleration/deceleration (A/D) forces acting on brain tissue and causing structural damage and functional disturbances on the different types of brain cells. This fact was discovered early in the history of TBI research by Denny-Brown and Russell, who observed that the loss of consciousness (LOC) associated with concussion was difficult to inflict when the movement of head during the application of the impact was restricted.¹⁵ Nervous tissue strains induced by both linear and rotational forces create spatiotemporal deformation gradients (Fig. 133-1). Because the brain is a viscoelastic organ with little internal structural support, it poorly tolerates such forces. 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 and gray matter of deep nuclei, in addition to the axonal tracts within the brain stem, are more vulnerable to rotational A/D forces. In the early 1940s, the effects of A/D forces on the brain were assessed on a physical gelatin model resembling gross brain’s physical properties, such as its volume, mass, and deformability.¹⁶ These studies were the first to describe how shear strains were caused by rotational A/D forces (also known as impulsive loadings) (Fig. 133-2). One decade later, the effects of A/D forces on brain tissue were analyzed by exhaustive postmortem neuropathologic studies performed on the brains of patients who had died from lethal road accidents.¹⁷ These studies showed that the predominant microscopic finding was 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. The term that Strich used to define this damage was “shearing injury,” because he thought that traumatic damage to white matter was caused by the shearing of nerve fibers at the moment of injury.¹⁷ Clinicopathological studies undertaken by Adams et al.¹³ endorsed Strich’s views, and Jennet and Plum considered this to be the most common cause of the vegetative state (VS) observed in many severely head-injured patients.⁹ In patients with shorter survival times (less than 6 weeks following the injury), the specific microscopic pattern of axonal degeneration consisted of the presence of retraction balls, interpreted as end swellings of proximal and distal segments of severed axons, which axoplasm had extruded.^18,19

FIGURE 133-1 Biomechanics of traumatic head injury I. Classic model of axonal shear injury caused by rotational A/D forces. Impulsive inertial loadings cause damage to axons grouped in bundles within white matter without direct impact to the skull. The severity of axonal injury depends on the course followed by the fibers and the predominant spatial plane of action of the rotational A/D force: sagittal (A), lateral/coronal (B), or axial (C). Different tissue densities of gray and white matter determine differences in the inertial displacement experienced by both tissues, causing maximal stress on a definite segment of the axons. Rotational A/D forces in the lateral plane cause the severest damage to the long axonal tracts coursing along the brain stem.^18,20

FIGURE 133-2 Biomechanics of traumatic head injury II. Classic model of spatiotemporal deformation gradient caused by A/D forces. Impact loadings inflicted on the freely moving head initiate a deformation wave that travels in the viscoelastic brain tissue, creating a spatiotemporal gradient.^15,16 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.³⁵

Diffuse brain injury usually depends on inertial loadings as a result of rapid head rotational motions of the brain, resulting from unrestricted head movement in the instant of injury.²⁰ Rapid A/D head movements deform white matter, inducing dynamic shear and tensile and compressive strains within the tissue (Figs. 133-1 and 133-2). A significant theoretical insight regarding the biomechanical effects of A/D forces on brain structure was made by Ommaya and Gennarelli in 1974.²¹ These authors proposed a “centripetal model” of severity of structural damage known as the Ommaya-Gennarelli model of TBI, which was based on experimental studies performed in subhuman primates.^20,21 This probably represents the most influential biomechanical model in the field of head injury, because it explains the damage caused by A/D forces, which are most common in traffic accidents. According to this model, the mechanical strain injury operates in the brain tissue in a “centripetal sequence,” in which the higher the magnitude of the injuring forces, the deeper the brain functional and structural damage observed. The sequence of damage begins at the surface of the brain and progressively affects deeper structures as the A/D forces increase in intensity. This model uses the principle that the severity of injury is mainly determined by the direction of force, with rotational forces causing the severest injuries. On the basis of the centripetal progression of injuries, the model introduced three critical predictions: (1) when the degree of trauma is sufficient to cause LOC, cortical and subcortical structures are primarily affected and show more severe damage than that found in the rostral brain stem; (2) damage to the rostral brain stem does not occur without severer damage of cortical and subcortical structures, since the mesencephalon is the deepest structure and the last one to suffer the effects of trauma; and (3) cognitive symptoms such as confusion and disturbance of memory can occur after TBI without LOC; however, the reverse cannot occur.

The Ommaya-Gennarelli centripetal model challenged the sustained view that the main mechanism producing traumatic unconsciousness after TBI was an isolated brain stem injury. The primary brain stem damage theory was supported in the 1950s and 1960s, when the ascending arousal system (AAS) was described by Moruzzi and Magoun.²² Experimental models of TBI on subhuman primates 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.^20,21 These findings were later confirmed in clinical studies, in which A/D loadings to the head in the coronal plane were observed to cause the severest injuries in humans subjected to motor vehicle accidents. Although early studies suggested that the primary site of brain injury in patients presenting with transient LOC and post-traumatic cognitive deficits was the brain stem, overwhelming neuropathologic evidence showed that most mild and moderate TBI caused damage to widespread areas of the cortex and the subcortical white matter.^13,23 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.²⁴

Biomechanical theories involving linear and rotational A/D loadings are considered by many authors to be incomplete and may not adequately explain injury to deeper cerebral structures in the absence of injury to more superficial cerebral structures. Early biomechanical work suggested that brain injuries occurred principally from pressure gradients developed within the brain at the time of the impact (Fig. 133-2), but more recent research has shown that head motions occurring at the moment of injury result not only in pressure waves but 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.

Historical Studies on TBI: Pioneering Research By Ramón y Cajal

The Nobel Prize winner Ramón y Cajal (1852-1934) was a distinguished pioneer in the scientific study of the histologic consequences of traumatic injuries on brain tissue (Fig. 133-3A).²⁵ He performed experimental studies on the brains of dogs and cats after severing the brain tissue with a scalpel and then studied the effect of the injury at different times up to 1 month following the injury. Ramón y Cajal described for first time the phenomenon of preservation after traumatic injury, which consists of the necrosis of cell elements distal to the lesion while these elements display perfect morphologic integrity. He also described for the first time the terminal clubs and hypertrophic stumps developing at the proximal endings of the surviving axons (retraction balls) and at the distal stumps of the preserved detached axonal segments (Fig. 133-3C).²⁶ Retraction balls were evident in the damaged tissue 24 hours after injury, and some thin axonal appendices were seen expanding out from each ball in the direction previously followed by the axon. In addition, 6 to 8 hours after injury, he observed varicosities along the fibers proximally to the retraction balls. Retraction balls and varicosities were observable during approximately the first week after the injury and then underwent a process of degeneration. Later, and nearer the cell bodies, new buds formed (late retraction balls). These persisted for 2 to 3 weeks and then disappeared, with some perhaps entering into the formation of the last living axon collateral, which became markedly hypertrophied.²⁵

FIGURE 133-3 Ramón y Cajal’s original contributions to the field of TBI. A, Self-portrait in his laboratory in Valencia (1884). B, Original illustration showing the structural gliovascular relationships between astrocytes and capillaries of white matter. Astrocyte end feet are contacting the capillaries’ surface. C, Original drawing showing the section of the cerebral cortex of a cat, 25 days old, that was sacrificed 20 hours after producing a cortical penetrating oblique wound with a knife, which passed beneath the layer of median pyramidal cells involving the segment of axon collaterals. Axonal varicosities (F) and retraction end balls (G-J) can be observed at the proximal and distal endings of severed axons next to the wound (R). In addition, necrotic vacuolar degeneration of the neuronal bodies closer to the wound is displayed (C), whereas neuronal bodies placed distant from the wound are preserved. D, Schematic drawing showing the possible propagation of currents in severed pyramidal neurons. Dendritic inputs would be transmitted through hypertrophic axon collaterals, which are developed from injured neurons above the lesion site. The arciform pyramidal cell (A), afferent fibers (E and F), hypertrophic collateral (a), part of the axon that has disappeared (b) are shown.

(From Ramón y Cajal S. Degeneration and regeneration of the nervous system. London: Oxford University Press, 1928.)

Therefore, the cortical pyramidal cells, which are those emitting long axons, were transformed after the traumatic injury into cells with short axons and hypertrophied collaterals (Fig. 133-3D). Ramón y Cajal proposed that the collateral hypertrophy is a compensatory phenomenon similar to the effects of an arterial ligature. Nevertheless, he did not know the fate reserved for the pyramidal cells with short axons. Months after the injury, he could not observe retraction balls or varicose fibers near the lesion; rather, he saw only smooth well-stained axons presenting all the signs of being normal conductors. He also observed that central tracts were incapable of regeneration and that although they had the property of producing new fibers, once the reconstructive movement is initiated, for unknown reasons the nerve sprouts lose their energy and suspend their growth. Nevertheless, he described neoformations (sprouting) in the pyramidal axons that were maximal in the second or third day after injury. However, in a few days these neoformative axon structures disappeared, and after 15 days, they were absent. In addition, he described the morphologic reactive changes in glial cells after the injury, consisting of the loss of capillary–neuroglial relationships (dislocation of perivascular astrocytes) and free migration of these cells to distant regions.²⁵

In summary, the major contributions made by Ramón y Cajal in the field of TBI were (1) the discovery of the retraction balls developing at the central stump of traumatized axons, (2) the description of post-traumatic compensatory hypertrophy of the initial collaterals of the axon and its branches, (3) the attempt at axon regeneration with the development of cephalopodic appendices, and (4) the description of reactive morphologic changes and free migration of glial cells toward noninjured capillaries after injury.

Neuropathology of TBI

In 1990, Adams summarized the neuropathologic postmortem findings obtained from one of the largest series of TBI patients providing a full postmortem examination. These series were part of the Glasgow database, which consisted of 635 fatal closed head injuries gathered between 1968 and 1982 in Glasgow, including 434 patients with a detailed neuropathologic study.¹⁸ One third of these patients had “talked” at some time after the injury.²⁷ 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 nonmissile head injury followed by secondary brain ischemia, which represented the second prognostic factor in importance after TBI.

According to the pathologic classification introduced by Gennarelli in 1987,²⁸ two major types of post-traumatic lesions could be differentiated in Adam’s series¹⁸: focal lesions, which are large enough to be identified by the naked eye, including cerebral contusions and intracranial hematomas, and diffuse injuries, which are all that cannot be macroscopically identified, including DAI, diffuse brain swelling, secondary hypoxic/ischemic brain damage, and diffuse vascular injury (Figs. 133-4 and 133-5). Overall, cerebral lesions caused by TBI can be viewed as a spectrum of injuries ranging from purely focal to purely diffuse, all brought about by A/D forces causing mechanical distortion to the head and nervous tissue. Focal brain injuries are usually 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 133-4 Types of intracranial post-traumatic lesions. Besides the DAI, the four major intracranial lesions are the EDH (A), acute SDH (B), contusions and intracerebral hemorrhages (C), and diffuse brain swelling (D). The lower row displays in detail the causal mechanism for each type of post-traumatic 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 ischemic 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 133-5 Neuropathology of TBI. 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, Brain stem axial slice, showing hemorrhagic lesions in the dorsolateral quadrants of the mesencephalon associated with severe DAI (Adams classification grade III). D, Post-traumatic axonal swellings revealed by APP immunostaining. E, Detail of axonal retraction balls.

(A to D, Courtesy of Dimitri Agamenolis, Akron Children’s Hospital, Akron, OH. E, Courtesy of Kar-Ming Fung, University of Oklahoma, Tulsa, OK.)

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.^14a Later experimental work by Denny-Brown and Russell¹⁵ and more recent work by Gennarelli et al.²⁰ 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 during life, 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 patients in a coma who do not present focal lesions.

Intracranial Hemorrhages

Intracranial hemorrhagic lesions represent the most common cause of clinical deterioration and death in patients who experience a lucid interval and usually develop in patients sustaining a skull fracture.²⁷ If the lucid interval is longer than 24 hours, the hematoma is said to be “delayed.” This occurs in 30% of head-injured patients with intracranial bleeding due to the development of a new hematoma after an initial normal CT scan. The three most important intracranial hemorrhagic lesions caused by TBI are EDHs, acute SDHs, and ICHs (Fig. 133-4A-C). EDHs corresponded to the 8% of lesions observed in the Glasgow database, whereas “pure” SDHs were diagnosed in 13% and ICHs in 15% of lesions. Nevertheless, a higher rate of 26% of patients presenting with SDHs associated with ICHs was observed 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 white matter deep to contusions (Fig. 133-5A). In a study performed in 1987 comparing 100 fatal head injuries with cerebral hematoma and 100 without cerebral hematoma, the cases with hematoma were observed to affect predominantly older patients.²⁹ Structural factors such as parenchymal atrophy and weaker holding of intracerebral small-caliber vessels may probably account for this observation. Other less frequent types of focal brain injuries are traumatic lesions of the corpus callosum, usually associated with DAI; pontomedullary rents or tears in the brain stem at the junction between the pons and the medulla, 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 sense of smell sometimes occurring after head injury because of avulsion of the olfactory nerves. For a detailed description of intracranial hematomas, refer to the section on surgical treatment of TBI.

Cerebral Contusions: Major Gray Matter Focal Lesions After TBI

Brain contusions represent frank disruptions of brain tissue, which are typically observed at the apex of cerebral gyri, appearing as coalescent petechial hemorrhages or streaks of hemorrhage with an eventual progression of bleeding into adjacent white matter (Figs. 133-4C and 133-5A).³⁰ 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 the trauma (Fig. 133-5A). These are the brain areas undergoing the strongest inertial impact against the rough and irregular prominences of the inner surface of the skull following abrupt A/D forces. Contusions are basically impact-related lesions occurring with short-duration and high-acceleration impacts.²⁰ 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 necessarily occurs, usually involving both the cortex and the subcortical area. Direct lacerations are caused by penetrating craniocerebral wounds, but indirect lacerations resulting from severe A/D shearing forces can be also observed.

Comprehensive studies performed by Lindenberg and Freytag in the 1950s³⁴ and by Oprescu in the 1960s³⁰ identified some specific types of contusions in the brains of head-injured patients dying a short time after the injury, such as contusions beneath skull fractures, coup contusions at the site of impacts (Fig. 133-4C), contrecoup contusions in regions distant to but not always opposite the impact site³¹ (Fig. 133-5A), herniation contusions, and finally, gliding contusions,³² which correspond to bilateral, focal, post-traumatic hemorrhages in the cortex and subcortical white matter of the superomedial parasagittal margins of cerebral hemispheres.³⁰ 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 the parenchymatous tissue develop a progressive secondary damage.³³ An initial vasodilatation followed by precapillary paralysis could be the triggering disturbance, causing endothelial leaking with blood extravasation that may lead to the development of true ICHs. In addition, the development of vascular thrombosis produces areas of necrosis that may become hemorrhagic, with a combination of necrotic and hemorrhagic brain tissue.³⁰ The classic study of Lindenberg and Freytag identified the presence of 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.³⁴ In contusive areas, neuronal bodies show vacuolar degeneration with chromatolysis and their axons show a varicose degeneration, a type of lesion originally described by a Ramón y Cajal in 1928 and later reported by Strich.^13,17,25 Glial alterations are constantly seen with hypertrophy, swelling of astrocytes, and the development of reactive hypertrophic microgliosis or “microglial stars.” 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.³⁵

Neuroradiologic Diagnostic Methods in TBI

CT Scanning

Cranial CT scanning is the imaging modality of choice for evaluation of a head-injured patient. It allows rapid assessment of the location, extent, and type of intracranial lesions caused by the head injury. With the lateral scout view and CT bone windows, skull fractures usually are well visualized, thus obviating the need for skull radiographic studies. Three major findings should be evaluated on a head-injured patient’s CT: (1) presence of intracranial hematomas, (2) appearance of basal cisterns at the midbrain level, and (3) presence of traumatic SAH. The status of the basal cisterns is related to the 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) (Fig. 133-6B). 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%.⁴

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 (Fig. 133-6 A₁ and A₂). A delayed or progressive brain injury, defined as new or progressive lesions seen on a follow-up CT scan, is observed in 45% of a large series of patients with closed head injury. McBride et al., based on a review of 154 consecutive patients with closed head injury requiring surgical intervention, 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.⁴⁹ Risk factors of 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. Of those patients with delayed brain injury, 55% had abnormal clotting studies, whereas only 9% of those patients whose follow-up CT scans did not worsen had abnormal coagulation studies.

FIGURE 133-6 Neuroradiology methods in TBI. A₁ and A₂, Axial CT scans of a 67-year-old man who suffered a fall and was admitted to the hospital with a GCS score of 14 points. A₁, A CT scan performed at admission shows a thin extra-axial collection (arrowhead) and a small ICH lesion in the right temporal lobe (double arrowhead). A₂, A CT scan performed 6 hours later, when the patient suffered a neurologic deterioration, shows a significant increased in the volume of the ICH lesion with uncal herniation (arrow). B, Evaluation of the basal cisterns on CT. B₁, A healthy control case (detail on the right bottom) shows all limbs open. B₂, Axial CT of a 25-year-old man injured in a traffic accident with a postresuscitiation GCS score of 6 points shows the three limbs of basal cisterns completely closed, indicative of diffuse brain swelling. C, CT scan of a 55-year-old woman with a minor head trauma due to a high-speed golf ball impact on the forehead, showing a compound depressed fracture with frontal sinus involvement, a depression greater than 1 cm, and gross deformity. The patient was operated on, with reconstruction of the anterior frontal sinus wall being carried out (surgical picture on the right bottom). D, Examples of the DAI stages using FLAIR MRI. D₁, Stage 1: An axial image demonstrates signal intensity changes in the lobar white matter. D₂, Stage 2: A sagittal image demonstrates signal intensity changes in the splenium of the corpus callosum. D₃, Stage 3: A sagittal image demonstrates signal intensity changes in the rostral brain stem. E, Representative fiber tractography (FT) images of the corpus callosum. The coloring of FT is displayed according to anisotropy coding, ranging between red (high anisotropy) and orange (low anisotropy). E₁, An FT image shows the corpus callosum from a healthy 32-year-old control case. E₂, An FT image from a 30-year-old patient after DAI shows interruptions in white matter fibers of the corpus callosum compared to the control case.

(D₃, From Skandsen T, Kvistad KA, Solheim O, et al. Prevalence of diffuse axonal injury in patients with moderate and severe head injury: a cohort study of early magnetic resonance imaging findings and 1-year outcome. J Neurosurgery 2010;113(3):556-563. E, From Sugiyama K, Kondo T, Oouchida Y, et al. Clinical utility of diffusion tensor imaging for evaluating patients with diffuse axonal injury and cognitive disorders in the chronic stage. J Neurotrauma 26: 1879-1890, 2009.)

Surgical Treatment of TBI

TBI treatment is an integrated team effort by surgeons and nonsurgeons. Probably the most important aspects of TBI care are nonoperative; however, the role played by neurosurgeons in the integral treatment of TBI patients remains critical, especially in making the appropriate decisions regarding whether to operate and, if operating, when to perform surgical procedures in advance to the progression of secondary damage.⁵⁴ Surgical management of TBI has long been based on clinical anecdotal practice, assuming that any intracranial mass lesion in a patient with progressive neurologic deterioration should be evacuated as soon as possible by craniotomy. The new paradigm of evidence-based medicine has extend to the establishment of scientific guidelines for the surgical treatment of TBI, published in 2006, which should help neurosurgeons make the most appropriate decisions by using a strong scientific background, in addition to personal anecdotal experience.^4,5 These guidelines were performed after a throughout analysis of the English-language TBI literature published since the use of CT scan. The appropriate articles were classified according to their scientific rigor in three classes of evidence with three associated levels of recommendation. No level I or II recommendation is provided by the surgical guidelines because of the lack of scientific class I or II evidence, mainly due to the ethical impossibility of carrying out prospective, randomized surgical trials. Consequently, guidelines can only formulate level III recommendations, reflecting unclear clinical certainty. As in all areas of clinical medicine, the optimal decision regarding treatment for an individual patient should not rigidly fall within a given recommendation of the guidelines but depend on a synthesis of the established knowledge based on guidelines and refined by the specific findings of the patient and the clinical judgment of the treating physician. A summary of the principal recommendations for surgical treatment of TBI lesions, together with the fundamental findings provided by the articles used for the elaboration of the guidelines, is provided in Table 133-4.

Surgical Treatment of Depressed Skull Fractures

Skull fractures are seen in 65% to 100% of patients with EDHs, in 18% to 60% of patients with SDHs, and in 40% to 80% of patients harboring parenchymal hematomas or contusions. The indications for operating on cranial fractures depend on whether or not the skin and galea overlying the fracture have been violated. A simple linear cranial vault fracture can usually be managed nonoperatively. Fractures depressed a depth less than the width of the skull itself, without an underlying mass lesion and not causing significant cosmetic deformity, can frequently be managed conservatively.

Depressed skull fractures can be classified in two major types: (1) simple cranial depressed fractures, which have no galeal disruption and are only surgically managed if the extent of depression equals or exceeds the thickness of adjacent intact bone or if there is an associated intracranial hematoma with mass effect that requires evacuation, and (2) compound depressed cranial fractures, which have galeal disruption and an overlying scalp laceration in continuity with the fracture site and are generally treated with debridement and surgical elevation.⁴ Some compound depressed cranial fractures may be treated nonoperatively if there is no clinical or radiographic evidence of dural penetration, significant intracranial hematoma, depression greater than 1 cm, frontal sinus involvement, gross deformity, wound infection, pneumocephalus, or gross wound contamination.⁵⁵ Several studies have also shown that the rate of postoperative infections is not increased by primary bone fragment replacement.⁵⁶ There is no difference in the rate of postoperative infection between patients undergoing surgical repair of the fracture within 8 hours and those treated after that time. Anticonvulsants should be administered prophylactically to these patients, who are associated with a 20% or greater risk of developing seizures. Recommendations for the surgical treatment of depressed skull fractures, according to the surgical TBI guidelines, are listed in Table 133-4.

One of the main operative goals of elevating an open depressed fracture is to achieve thorough debridement. If the skin edges are macerated, contaminated, or severely contused, excision of the involved edges is indicated, and the surgeon should anticipate the need for a pericranial graft with the aim of preserving as much pericranium as possible to cover the bone fragments at the time of closure. Rotational flaps are rarely necessary but should be anticipated if large areas of the scalp have been denuded at the time of injury. A small bur hole placed adjacent to the fracture is usually necessary to identify the epidural space and begin gentle piecemeal removal of the bone fragments. Orderly, safe removal of the bone fragments should be done with the aid of a punch or rongeur and without further injury to the underlying dura or cortex. In general, unless the wound is old or grossly contaminated, the bone fragments are replaced at the end of the procedure after vigorous irrigation and cleaning. If there is an underlying dural laceration, the craniectomy must expose the entire extent of the dural opening, and repairing this defect in the dura is the most important part of the procedure. Dural repair should be watertight and may require grafting.

If the paranasal sinuses are involved by a depressed fracture, the goals of treatment are correction of the cosmetic deformity and prevention of a CSF fistula, regardless of whether the fracture is simple or compound. Depressed fractures of the anterior wall of the sinus do not result in a CSF fistula unless there is also a fracture of the posterior wall and a tear in the adjacent dura. A bicoronal scalp is fashioned, the pericranium is elevated as a separate layer, and the depressed fragments are elevated. Then the sinus mucosa is exenterated to prevent the formation of a mucocele, using a small drill if necessary. Next, the residual cavity can be filled with temporalis muscle and fat (Fig. 133-6 C). A pericranial graft can then be reflected over the sinus and sewn to the dura to further isolate it from the intracranial contents. The bone fragments comprising the anterior wall of the sinus are wired together and secured to the skull. The bone fragments of the posterior wall do not need to be replaced.

Post-Traumatic Intracranial Hematomas: Surgical Versus Nonoperative Management

The formation of intracranial hematomas after a head injury is a common occurrence. Among the 746 severely head-injured victims included in the TCDB, 37% of patients underwent surgery for removal of an EDH, SDH, or intracerebral hematoma (ICH).⁵⁷ To detect hematomas at an early stage, it is essential to identify the risk factors that increase the changes that a given patient will be harboring an intracranial hematoma. They consist of the presence of a skull fracture on radiograph, any neurologic dysfunction, a seizure or severe headaches and vomiting, and a decrease in the level of consciousness. Patients with blood coagulation disorders should be observed particularly carefully for progressive enlargement of hematomas, and the clotting disorders must be vigorously treated. Overall, nonoperative management of SDHs and EDHs should be considered only if the patient is fully conscious, the extra-axial mass lesion is the single dominant lesion (i.e., there are no multiple contusions or potentially significant contralateral mass lesions, which may be preventing midline shift), and there are no features of mass effect, such as midline shift greater than 3 mm, or basal cistern effacement. Finally, there are situations in which the dismal clinical status of the patient warrants a nonoperative course despite the presence of a radiographic surgical lesion. Such cases include the adult patient who is moribund and flaccid with a GCS score of 3 points, nonreactive and dilated pupils, and no spontaneous respirations.⁵⁸ Similarly, in patients older than 75 years of age with a GCS score of 5 or fewer points, a nonoperative course usually should be taken, given their consistently poor outcome with or without surgery.

High ICP and ICP Monitoring in TBI

The brain is housed in a rigid cavity and has a limited ability to compensate any volume occupation caused by intracranial hemorrhages or the development of swelling. Clinical examinations are unreliable unless the patient has progressed to brain stem herniation. The most accurate way of assessing ICP is to insert a monitor to allow the clinician to anticipate irreversible brain damage by a prompt medical or surgical intervention. There is substantial evidence that ICP monitoring may improve outcome, because it helps in earlier detection of intracranial mass lesions and guides therapies to control intracranial hypertension. About two thirds of patients with severe head injury have no significant mass lesion on the initial CT scan, but at least 80% demonstrate high ICP.⁵⁹ It is generally accepted that severely head-injured patients (GCS score 3-8 points) with abnormal scans should undergo ICP monitoring. Effaced cisterns are associated with high ICP in more than 70% of cases, and mandatory ICP monitoring is advocated in such cases. The prevalence of postoperative intracranial hypertension is extremely high (greater than 75%) in patients who were in a coma before removal of an intracranial hematoma. In such patients, therefore, an ICP monitoring device should be inserted at the end of the procedure.

The gold standard method for measuring ICP is an intraventricular device connected to a fluid-coupled catheter with an external strain gauge (ventriculostomy catheter), because it not only monitors ICP but also provides CSF drainage to lower ICP (Fig. 133-7A-C). Nevertheless, many centers tend to use intraparenchymal probes, especially when the ventricular size is small and it is expected to need a high number of passes. This device should be inserted through a bur hole and skin incision separated from the craniotomy. A twist drill is usually made just anterior to the coronal suture in line with the pupil. Following the opening of the dura with a blunt stylet, the transducer tip is directly placed in the brain parenchyma at a distance of 2 to 3 cm into the brain parenchyma (Fig. 133-7D).

FIGURE 133-7 ICP monitoring technique. A to C, Technique for implanting a ventricular catheter, representing the landmarks used for ventriculostomy catheter placement into the right frontal horn. A, A short incision is made in the midpupillary line. An opening in the skull is made with a twist drill 3 to 4 cm lateral to the midline, 3 cm posterior to the hairline, and 2 cm anterior to the coronal suture. B and C, Following the opening of the dura, a ventriculostomy catheter is placed, aiming at the medial canthus of the ipsilateral eye and the tragus of the ipsilateral ear. The tip of the ventricular catheter is advanced 5 to 7 cm from the surface of the skull. D, An intraparenchymatous ICP probe is recommended when the ventricular size is small: a small-diameter drill is used to open the skull, and then a screw is fixed to the skull and the probe is passed through it until the transducer tip is placed about 3 cm into the brain.

The criteria for how long to monitor ICP are not firmly established. Post-traumatic swelling, edema, and progression of hemorrhagic lesions typically are maximal within 48 to 96 hours of injury. However, delayed increases in ICP can occur and may occur in up to 30% of cases between 3 and 10 days after injury, especially in patients with contusions or SDHs. Discontinuation of ICP monitoring is reasonable in patients who show significant and steady clinical improvement to a GCS score of more than 9 points and maintain normal ICP without specific therapy or with only minimal sedation for at least 24 hours. Even if these criteria are met, a longer period of observation may be warranted when the initial diagnosis is acute SDH or multiple contusions, in patients with significant vasospasm evidenced by transcranial Doppler, and in patients with major systemic derangements.

Surgical Timing in Post-Traumatic Lesions

In general, the decision regarding whether or not to proceed with surgical evacuation of a post-traumatic hematoma depends on the patient’s clinical condition, neurologic status, and imaging findings. Clinical features indicating high ICP or any impairment to the level of consciousness, oculomotor paresis ipsilateral to a sizable hematoma, bradycardia, severe headache, repeated vomiting, and/or arterial hypertension. CT features suggesting raised ICP are shift of brain structures, obliteration of all subarachnoid CSF spaces, dilatation of the lateral ventricle contralateral to the hematoma, and hematomas of large size. A prompt surgical evacuation is essential for masses producing brain stem compression because of the risk of irreversible ischemic brain damage. In these cases, the sooner the decompression is achieved, the greater the possibility of good recovery. There is clear evidence that delayed evacuation of an EDH/SDH causing significant midline shift once clinical deterioration is present is associated with much poorer results, especially if the evacuation is later than 2 to 4 hours of the onset of the coma.⁶⁰

Greater controversy exists over when to evacuate parenchymal brain contusions and traumatic ICHs and whether such removal is helpful in controlling ICP and improving outcome.⁶¹ Miller et al., in their experience with more than 200 severely head-injured patients, contusions, and traumatic hematomas associated with the highest incidence of poor ICP control despite their surgical removal, recommended an initial nonoperative management for such lesions.⁶¹ Other authors believe that early surgical removal of larger hematomas and cerebral contusions provides early control of ICP and helps prevent the cascade of secondary damage. Temporal lobe hematomas are especially likely to cause brain stem compression at low ICP with little midline shift and should be evacuated sooner than other locations. An initial conservative approach is warranted, however, when eloquent cortex is involved. Similarly, intracranial hematomas confined to deep white matter or the basal ganglia are best managed without surgery.

Acute EDH

An acute EDH develops between the dura mater and the inner table of the skull and is reported in 2.5% to 5% of head-injured patients (Fig. 133-4A). EDHs adopt a lens-shaped or biconvex morphology as the periosteal layer of dura is stripped from the inner table of the skull by the bleeding. The classic and most lethal type of EDH is caused by a skull fracture crossing the groove in the temporal bone containing the middle meningeal artery. These hematomas generally accumulate rapidly, although a delayed stepwise progression over hours may also occur. EDHs may have also a venous origin, either from diploic veins or from bridging veins torn along their course into venous sinuses. These lower pressure hematomas develop slowly and are often self-limited, but no reliable imaging signs can be used to assist in their prediction, and this subtype should be considered dangerous. Some EDHs accumulate from rebleeding, accounting for up to 30% of all EDHs in some series.⁶² Dural stripping by the blow itself has been postulated to be the alternative presumed mechanism. Epidural collections arising solely from skull fracture bleeding are most often small and most frequently do not expand in the absence of damage to an adjacent sinus or coagulopathy. Nevertheless, nonoperative management based on anticipated stability should be supported by serial imaging.

The “classic” lucid interval consisting of a brief LOC caused by the blow per se followed by an awaken period and late deterioration due to rising ICP and mass effect (patients who “talk and die”) only occur in a minority of cases, approximately 15% to 30%.⁶³ Between 20% and 55% of the patients are comatose on admission or immediately before surgery.^62,64 Although most EDHs are diagnosed on the initial CT scan, the clinician must remain alert to the possibility of an EDH that develops or rapidly enlarges after an apparently negative scan. A vertex hematoma may be missed on a routine axial CT scan, but a coronal reconstruction should identify the lesion.

EDHs are not usually associated with underlying parenchymal damage, so their early surgical evacuation is highly successful. Global mortality of a surgically treated EDH is approximately 10%.^62,64 The surgery is usually an emergency, especially in patients in a coma at the time of the diagnosis, as the duration from time of injury to treatment is an important determinant of prognosis. Other factors in determining the outcome are age, depth of coma, degree of midline shift, and size of hematoma. The mortality rate and outcome after evacuation of an EDH is directly related to the level of consciousness before surgery, ranging from 0% for patients conscious at the time of operation to 27% for patients presenting with the classic lucid interval and reaching 50% for patients who never regain consciousness after the impact.