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Behavioral Consequences of Traumatic Brain Injury

Chapter 13

BEHAVIORAL CONSEQUENCES OF

TRAUMATIC BRAIN INJURY

EDWIN A. WEINSTEIN, M.D.*; ANDRES M. SALAZAR, M.D.†; AND FRANKLIN D. JONES, M.D., F.A.P.A. ‡

INTRODUCTION

PATHOGENESIS

Closed-Head Injury

Penetrating Brain Injury

POST-TRAUMATIC STRESS DISORDER

MILD HEAD INJURY

MODERATE AND SEVERE HEAD INJURY

Post-Traumatic Amnesia

Anosognosia

Confabulation

Environmental Disorientation

Temporal Disorientation

Reduplication

Mood Disorders

NEUROPSYCHOLOGICAL ASSESSMENT

Attention

Memory

Language

Calculation

Constructional and Visuospatial Skills

Praxis

Abstraction

Executive Functions

LONG-TERM SEQUELAE

Cognitive Changes

Affective Disorders

Psychoses

TREATMENT

Behavioral Management

Pharmacological Management

OUTCOME

PREDICTABILITY AND PREDISPOSITION

SUMMARY AND CONCLUSION

*Consultant in Neurology, National Naval Medical Center, Bethesda, Maryland; Consultant in Psychiatry, Walter Reed Army Medical Center,

Washington, D.C.; Formerly Chief, Fifth Army Neuropsychiatric Center (World War II)

†Colonel, Medical Corps, U.S. Army; Professor of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland;

Director, Defense and Veterans Head Injury Program

‡Colonel (ret), Medical Corps, U.S. Army; Clinical Professor, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Past

President and Secretary and current Honorary President of the Military Section, World Psychiatric Association; formerly Psychiatry and

Neurology Consultant, Office of The Surgeon General, U.S. Army
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John O. Wehrle Purple Heart 1966

John O. Wehrle depicts a serviceman in Vietnam who has received his Purple Heart in a Surgical Intensive

Care Unit. In combat settings, traumatic brain injury often occurs in conjunction with other injuries, as

shown in this painting.

Art: Courtesy of US Center of Military History, Washington, DC.
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Behavioral Consequences of Traumatic Brain Injury

INTRODUCTION

Traumatic brain injury (TBI) is the leading cause

of death and disability in young adult Americans

today.1 The incidence of TBI requiring hospitalization is approximately 200/100,000/y; about 75,000

persons die and another 75,000 are permanently

disabled each year. Similarly, in the Vietnam conflict, head and neck wounds accounted for 40% of

all battlefield fatalities, and for about 11% of all

surviving casualties. Yet, largely because it affects

the young and can result in prolonged convalescence and a lifetime loss of earnings, the impact of

TBI is greater than most other injuries. The total

peacetime economic cost of TBI in the United States

has been estimated at over $25 billion per year.

A number of underlying themes will be emphasized in the following discussion of TBI, particularly as a basis for understanding its neuropsychiatric consequences. First, it must be recognized

that TBI represents a spectrum of disorders, with

regard to mechanism of injury (penetrating vs

closed-head injury), severity of injury, and pathology (see below). Secondly, TBI is a dynamic process. The acute evolution of secondary cellular

injury and brain swelling in the first hours posttrauma offers a therapeutic window of opportunity

that is the subject of intense study and rapid development in the field at present. Postacutely, the

natural history of TBI is one of recovery, often to a

remarkable degree in young adults. However, this

recovery often represents compensation for functions lost, and its pace should not lull health care

providers into ignoring the long-term behavioral

deficits and maladaptations commonly seen in these

patients. Third, “outcome” should be considered a

summation of a variety of factors, including

not only physical and cognitive recovery but

behavioral and psychosocial reintegration as well.

Fourth, preinjury status is a major determinant of

final outcome after TBI; this has been reemphasized

in a recent study showing that preinjury intelligence was the single most important determinant of

cognitive performance in a large cohort of headinjured Vietnam veterans.2 In this chapter, the

current understanding of the pathogenesis of TBI

will be briefly reviewed, with some comments on

experimental treatment. The phenomenology and

the cognitive, neurobehavioral, and psychosocial

outcome of head injury will be discussed, as will be

the behavioral and pharmacological aspects of

therapy.

PATHOGENESIS

Closed-head Injury

Given that TBI results in a spectrum of pathologies, all of which can affect outcome, it is relevant to

review the various components here. Over the past

decades there has been movement from conceptualizing the pathology of closed-head injury (CHI) in

terms of hematomas and “coup-contrecoup” contusions to a four-component classification.3

 Three

parallel components were initially identified: (1)

focal injury, (2) diffuse axonal injury (DAI), and (3)

superimposed hypoxia or ischemia. More recently,

(4) diffuse microvascular injury with loss of

autoregulation has been implicated as playing an

important role in the acute stage of moderate and

severe head injury. All of these pathological features have been reproduced in animal models of

angular acceleration without impact; and possibly

except for diffuse axonal injury, all are also features

of penetrating head injury (PHI).4

Focal Injury

Focal tissue disruption, swelling, contusions, or

hematomas at the site of impact or penetration

result in focal cortical neurologic deficits referable

to that area (eg, aphasia, hemiparesis). By far the

most common location for contusions after deceleration injury is in the orbitofrontal and anterior

temporal lobes, where the brain lies next to bony

edges. This is also an area rich in limbic connections

governing mood, emotions, and memory. Thus, a

relatively typical pathological picture is often seen

in most closed-head injuries (CHIs). Among its

most troubling clinical sequelae are attentional,

memory, and behavioral abnormalities, which may

be referable to the frontal and temporal lobe injury.

Subdural hematomas are most common with rapid

decelerations such as occur with impact after a fall,

especially in the aged, and are usually due to rupture of bridging veins; they appear to be much less
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common after penetrating head injury. Delays

longer than 4 hours in the surgical management of

hematomas appear to worsen prognosis significantly. Delayed hematomas as well as bleeding into

contusions are particularly important in the socalled “talk and die” patient, who may initially

appear to be at low risk but then deteriorates unexpectedly.5

Diffuse Axonal Injury

Diffuse axonal injury (DAI) is one of the most

important causes of prolonged coma and persistent

severe neurological deficit in CHI. Originally described as a “shearing” injury of axons, it was characterized by axonal “retraction” balls microscopically in the hemispheric white matter, corpus

callosum, and brain stem.6,7 Recent work with mild

to moderate fluid-percussion injury in animal models, however, shows that the typical light microscopic histopathology of DAI showing axonal shear

may not emerge until 12 to 24 hours postinjury. The

only early abnormality is a relatively subtle focal

intraaxonal disruption seen on electron microscopy,

with an intact axon sheath. This leads to a disturbance of axonal flow, accumulation of transport

material with axonal ballooning proximal to the

injury, and then eventual delayed severing of axons

12 to 24 hours later.8,9 The role of alterations in

calcium metabolism at the injured site on the axon

may be particularly important. One obvious clinical implication of these findings is that there may be

a potential 12 to 24 hour window of therapeutic opportunity postinjury during which future treatments may

prevent total axonal disruption. Another important conclusion is that DAI can be demonstrated

even after “minor” head injury, and occurs even in

the absence of morphopathologic change in any

other vascular, neural, or glial elements. This confirms earlier uncontrolled pathological studies in

humans and makes such axonal damage a possible

organic basis for the “postconcussion syndrome”

and perhaps for the cumulative effects of repeated

concussion, as seen in some boxers.10

Interestingly, a major feature of the pathology of

dementia pugilistica is the presence of neurofibrillary

tangles (NFT). NFT in Alzheimer’s disease and in

other conditions such as Guamanian amyotrophic

lateral sclerosis, have been postulated to result from

abnormalities in axonal flow, in the latter case probably related to aberrant calcium metabolism.11 While

classical Alzheimer plaques are not seen in this

condition, recent studies show plaquelike structures that stain with monoclonal antibody to the

beta amyloid precursor protein both chronically in

boxers and acutely after severe head injury.12–14 It is

unknown whether repeated trauma might alter the

secretion, metabolism, or structure of the amyloid

precursor protein in such a way as to lead to plaque

and NFT formation or whether the phenomenon of

lipid peroxidation, which is discussed further in

this chapter, may also play a role in this process.

Hypoxia-Ischemia

The classical pathology of hypoxia-ischemia, involving mainly the hippocampus and the vascular

border zones of the brain, is frequently superimposed on the other pathological features that are

more specific for TBI. The traumatized brain is

particularly sensitive to hypoxia-ischemia.15 When

present, such pathology, including the concomitant

hippocampal necrosis, can obviously become a major determinant of ultimate clinical outcome, particularly with regard to post-traumatic memory

disorders. Recent improvements in the survival of

the TBI patient have largely resulted from recognition of the importance of this component and its

prevention, especially through the development of

emergency resuscitation and transport systems.

Microvascular Change

Diffuse microvascular damage has also been recently implicated as a major component of both

closed and penetrating TBI. Depending on the

severity of the trauma, early physiological changes

include an early loss of cerebrovascular autoregulation with a decreased response to changes in

CO2 and perfusion pressure, and an initial transient

systemic hypertension (probably related to release

of catecholamines).16,17 The loss of autoregulation

makes the brain particularly susceptible to fluctuations in systemic blood pressure. For example,

systemic hypertension can increase the risk of

vascular dilatation with hyperemia and brain swelling, or otherwise tolerable hypotension can result

in ischemic damage. In addition, altered vascular sensitivity to circulating catecholamines or

acetylcholine can lead to vasoconstriction and further focal ischemia or reperfusion injury (“noreflow” phenomenon). Recent blood flow studies

have confirmed a relative cerebral ischemia in a

large proportion of TBI patients acutely.18 Such

changes may be susceptible to pharmacological

interventions.
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Behavioral Consequences of Traumatic Brain Injury

The pathology appears to be biphasic, with an

early, transient alteration of the blood-brain barrier

(BBB), and a more delayed (6 plus h) endothelial

change.19,20 Diffuse perivascular damage with

astrocytic footplate swelling is a prominent feature

at both the light and electron microscopic levels

within minutes of high-velocity gunshot wounds

as well as after acceleration injury in nonhuman

primates. The basic cause of this swelling was

initially thought to be a break in the endothelial

BBB, but recent studies have demonstrated an increased pinocytotic transfer of horseradish peroxidase marker with intact endothelial tight junctions.21 The astrocytic swelling is usually maximal

at 30 to 60 minutes and is much reduced by 6 hours

postinjury; it is thought to represent an initial reaction to the altered transport across the BBB. It

should be emphasized, however, that the classic

concept of BBB breakdown and cerebral edema

post-TBI is undergoing radical revision, particularly in the absence of evidence for increased brain

water after either uncomplicated PHI or CHI.22

Cerebral edema, per se, may become more of a

factor when hypoxia, ischemia, or both complicate

the injury.

The second microvascular phase is one of endothelial change, including formation of intraluminal

microvilli or blebs, which then break to form endothelial craters. This peaks at about 6 hours postinjury

but usually persists as long as 6 days. Although the

clinical significance of these changes is still not

known, they are probably related to the altered

microvascular sensitivity to circulating neurotransmitters, to the loss of autoregulation, and perhaps

to secondary brain swelling. Recent studies have

shown an associated loss or inhibition of various

endothelial hormones including endothelium-derived relaxing factor (EDRF).

EDRF was first described almost a decade ago

and has recently been identified as nitric oxide.23

Inhibition of EDRF may be responsible for prolonged vasoconstriction and perhaps the so-called

“no reflow” phenomenon leading to secondary focal ischemia, while loss of other factors may have

the opposite effect. One of the principal inhibitors

of EDRF in TBI appears to be the superoxide radical,

which has also been shown to have a vasoconstrictive effect in experimental models.24,25

Application of free radical generators (such as

xanthine-xanthine oxidase) to the intact pial surface

of nontraumatized animals reproduces very similar

changes to those seen after TBI.26,27 Superoxide

dismutase will prevent or reverse this vascular hyperactivity experimentally, suggesting that the vasoconstrictive effect is mediated through the superoxide radical itself.

Secondary Tissue Injury

The picture of a TBI patient who is initially relatively stable and awake or in light coma and then

deteriorates and dies is all too common. While

some of these cases represent delayed hematoma

amenable to surgery, most are probably related to

an uncontrolled brain swelling that does not respond to conventional management. Over the past

decade, delayed secondary injury at the cellular

level has come to be recognized as a major contributor to this phenomenon and to the ultimate tissue

loss after TBI.

Understanding of the pathogenesis of secondary

injury is thus particularly important to the presentday management of the head-injured patient. As

suggested above, a cascade of biochemical and

physiological events is set in motion in injured

tissue. This includes changes in arachidonic acid

metabolites such as the prostaglandins and the

leukotrienes,28 the formation of oxygen free radicals,16 changes in neuropeptides,29 electrolytes such

as calcium and magnesium,30 neurotransmitters such

as glutamate or acetylcholine,31,32 lactic acid,33 various kinins, and a leukocyte response with release of

lymphokines such as interleukin-1.34

These products can result in progressive secondary injury to otherwise viable brain tissue through

a number of mechanisms: (a) by altering vascular

reactivity and producing further ischemia, (b) by

producing brain swelling (hyperemia, edema, or

both), (c) by injuring neurons and glia directly or

activating macrophages that result in such injury,

or (d) by establishing conditions favorable to secondary infection. In other words, much of the

ultimate brain loss after PHI may be due not to the

injury itself, but to an uncontrolled vicious cycle of

biochemical events set in motion by the trauma.

Oxygen Free Radicals and Lipid Peroxidation

Perhaps the most important path of cellular injury in TBI involves oxygen free radicals. These are

produced early in ischemic and traumatic tissue

injury, both in the central nervous system and elsewhere.16,35,36 The superoxide radical (O2•) is formed

through a variety of mechanisms, including normal

mitochondrial respiration, the xanthine oxidase and

arachidonic acid pathways, or by activated leuko-

–
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cytes. The phenomenon of receptor-mediated phospholipase activation may play an important role in

the initial release of arachidonic acid after both

trauma and ischemia.

The superoxide radical results in tissue injury in

its own right through its effect on the microvasculature. However, when combined with its own metabolite, hydrogen peroxide, in the presence of free

iron, it forms the hydroxyl radical (OH•). This

reacts with the abundant lipids in the brain in the

process of lipid peroxidation, with further release

of arachidonic acid and a vicious cycle in which

more free radicals are produced through the

cyclooxygenase pathway (along with prostaglandins), overwhelming natural free radical scavenging mechanisms. There is a marked rise in lipid

peroxidation markers as early as 2 hours postinjury,

and lasting at least 5 days in severely head-injured

patients. This confirms the ongoing nature of delayed secondary cellular injury in the postacute

period, as well as the possibility that the postinjury

therapeutic window of opportunity may be considerably longer than has been thought until now.37

Pharmacological intervention to reduce the formation of free radicals, or to scavenge those already

formed, or both would thus be expected to reduce

ultimate tissue injury. Animal models have confirmed this potential benefit in several systems.

Because free radicals are formed through a number

of biochemical pathways, a variety of drugs or drug

combinations may be useful to control them. These

include the use of steroids to inhibit lipid

peroxidation and the release of arachidonate

(megadose methylprednisolone and especially the

nonglucocorticoid 21-aminosteroids or “lazaroids”);38 α-tocopherol (Vitamin E) and its analogues;39,40 cyclooxygenase inhibitors to block prostaglandin formation; xanthine oxidase inhibitors

such as allopurinol;41,42 iron chelators such as

desferrioxamine;43 enzymes such as superoxide

dismutase and catalase;27,44 and various other free

radical scavengers such as mannitol and dimethyl

sulfoxide.

Superoxide dismutase (SOD) may be particularly attractive as therapy because it scavenges all

superoxide radicals regardless of their source. In a

particularly relevant model using intracranial balloons in dogs to mimic subdural hematoma, SOD in

doses equivalent to those being used in current

clinical pilot trials practically eliminated BBB breakdown and postdecompression pathological change

when compared to conventional therapies, and decreased mortality from 80% to 0%.44 Clinical pilot

studies have shown a 50% decrease in mortality in

severely head-injured patients treated with SOD,

but final conclusions must await a larger controlled

study.45

Penetrating Brain Injury

The majority of casualties with penetrating head

wounds who survive long enough to reach the

hospital level have been injured by fragments from

an explosive munitions.46 Penetrating wounds, as

noted, share a number of the features of moderate

and severe closed-head injuries. These include the

frequent involvement of more than one lobe; contusions, hematomas, and hemorrhages, some distant

from the point of penetration; edema; hypoxia,

ischemia, or both; and diffuse microvascular injury

with loss of auto-regulation. There are, however,

some important clinical differences.

Whereas the soldier with a moderate or severe

acceleration/deceleration closed-head injury is

by definition unconscious, and the severity of the

injury can be graded by the Glasgow Coma Scale,

a slight majority of the men who suffered a penetrating head injury in Vietnam did not lose consciousness, or did so only briefly. Of 342 subjects in

the Vietnam Head Injuries Study, 53% had no

or only momentary unconsciousness, and only

15% had prolonged unconsciousness.47 While retrograde and anterograde amnesia are almost invariably present in moderate and severe closedhead injury, 121 of the 342 patients in the Vietnam

study reported having had no amnesia. Penetrating

head injuries have a much higher incidence of seizures with figures up to 50%. The rate in closedhead injuries in which the dura mater has not been

pierced runs from 2% to 11% depending on the

complications.

The neurological deficits following penetrating

brain injuries are more focal and variable, depending, as most do, on the particular cortical area involved. The deficits include aphasia, hemiplegia,

and hemiparesis; cortical sensory disturbances; visual field defects; and impairments in visuospatial

processing. Closed-head injury patients with damage to frontal and temporal limbic structures are

more apt to manifest long periods of disturbed

consciousness and impairments of memory, attention, personality, perception of reality, and social

behavior. These differences are not absolute. Patients with closed-head injuries may have focal signs

depending on the point of impact, and penetrating

injuries of the basilar and other deep structures can

result in prolonged unconsciousness and memory

loss.47
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Behavioral Consequences of Traumatic Brain Injury

POST-TRAUMATIC STRESS DISORDER

The potential interaction between traumatic brain

injury and post-traumatic stress disorder (PTSD)

remains unclear. The second author has had the

opportunity to address this issue in a large cohort of

head-injured Vietnam veterans and a group of uninjured Vietnam combat veteran controls participating in the Vietnam Head Injury Study.48 The

data indicate that 15% of head injured and 8% of

controls fit the criteria previously established for

post-traumatic stress disorder in non-brain-injured

subjects on the Minnesota Multiphasic Personality

Inventory.49 Neither total brain volume loss, nor

lesion location, nor post-injury cognitive change

showed a relationship with PTSD scores.

Head-injured PTSD subjects reported relatively

decreased psychological support from community

and government upon their return from the Vietnam theater, whereas control PTSD subjects complained more often of a general negative impact of

the war on their lives. As expected, PTSD correlated with other measures of psychopathology, especially depression, in both controls and head-injured men. The findings suggest that while many

factors may contribute to the development of PTSD,

the brain injury itself may play a less important role

than other psychological variables. Treatment of

PTSD is addressed in Chapter 16, Chronic PostTraumatic Stress Disorders.

MILD HEAD INJURY

Mild head injury (concussion) has been defined

as an acceleration/deceleration closed-head injury,

almost always associated with a period of amnesia,

usually with a momentary interruption of, or brief

change in, consciousness, and followed by a characteristic group of symptoms, including headache,

dizziness, poor memory and concentration, fatigue,

and irritability.50 The injuries are incurred mainly

as the result of motor vehicle injuries, assaults and

falls.

The term concussion has been largely replaced

by the designation mild or minor head injury because over the past 20 years it has been shown that

such injuries may be associated with neuroanatomical and neurophysiological abnormalities,

and with deficits in neuropsychological tests. Concussion, on the other hand, had been thought to

involve a shaking up of the contents of the skull

without any structural lesions. Animal models of

concussion, however, have shown diffuse axonal

damage, and magnetic resonance imaging (MRI) as

well as positron emission tomography (PET) and

power-spectral electroencephalogram (EEG) have

repeatedly demonstrated structural, metabolic,

and functional changes in humans with mild head

injury.

Neuropsychological tests have shown impairment in sustained attention, delayed memory, and

impaired ability to process multiple items of information simultaneously.51,52 Such deficits usually

clear over a 3-month period in patients without a

history of previous head injury or drug abuse.53

These and other data indicate that the postconcussion syndrome cannot be explained solely on

a psychological basis, as the result of emotional

trauma, and a desire for legal compensation. The

symptoms appear in the great majority of patients

who have sustained mild head injuries. They occur

frequently following sports-related injuries, in

which case the motivation to return to athletic competition is high.54 The symptoms of patients seeking

legal redress may clear before settlement55 and a

lump sum award does not necessarily cure the condition.56

There are a number of reasons, however, why the

symptoms cannot be accounted for on a traditional

lesion deficit model, and why psychological and

social factors are relevant. The severity of the brain

injury as measured by the duration of the period of

unconsciousness and the length of the post-traumatic amnesia does not correlate with the number

and intensity of such symptoms as headaches, difficulty in concentration, irritability, noise sensitivity, and fatigue.57 Even though test scores return to

normal, and MRI abnormalities (if they have been

present) clear, symptoms may persist.

The early symptoms that appear immediately or

shortly after the injury, such as headache, dizziness, drowsiness, nausea, and blurred vision are

thought to be a direct result of the brain injury.

Later manifestations that come on a few weeks

after injury include difficulties in memory (aside

from the retrograde amnesia [RA] of which patients

seldom complain) and concentration, fatigue,

insomnia, irritability, noise sensitivity, and

depression that can be regarded as responses to

the stresses of the patient’s cognitive and attentional deficits, and their anticipated consequences.
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The persistence of headaches and dizziness or

vertigo in the absence of signs of vestibular dysfunction indicates an association with anxiety or

depression.

Despite the trauma, the patient is in some respects under less stress in the period immediately

following the accident. He is likely to have been

relieved that his injury was not serious, and to have

been assured that he will recover completely. There

is more stress when he returns to work and finds

that his mental capabilities are reduced. The increased effort required causes fatigue, and he may

become anxious and depressed. He may face the

skepticism and disapproval of those who believe

that he should have recovered from an apparently

minor injury. These features are highly relevant to

treatment.

The overall aim of treatment is the prevention of

a secondary traumatic neurosis. If there is evidence

of brain damage, the patient should be so informed.

There is nothing more frustrating for the conscientious, intelligent patient than to be told that there is

“nothing wrong” with him, a statement that suggests that he is malingering or not trying. Fatigue is

the most troubling symptom interfering with return to work. The relationship of fatigue to diminished mental capacity and stress should be discussed with the patient and his supervisors. To

control the situation, a graded work schedule should

be instituted so that the patient can work within the

limits imposed by his fatigue. Periodic neuropsychological testing may help to monitor progress.58

A graded return to full workload over a period of 4

to 8 weeks is suggested.

The severity of a head injury is evaluated by the

findings on computed tomography (CT) and MRI

scans, the depth of coma, the duration of the loss of

consciousness, and the length of the anterograde

amnesia (AA). Degrees of severity are differentiated as follows:

• Moderate and severe TBI lesions include

contusions, hemorrhages, and hematomas,

which are rare in mild head injury.

• Mild head injuries have scores of 13 to 15 on

the Glasgow Coma Scale on which verbal,

ocular, and motor responses are graded,

while moderate head injuries score between

9 and 13, and severe head injuries place

below 9.

• The loss of consciousness in moderate and

severe TBIs is measured in hours and days,

rather than in seconds and minutes as in

mild head injuries.

• The AA in mild head injury is usually a

matter of seconds or minutes, whereas in

moderate and severe brain injuries there is

an AA of days and weeks. Severe head

injuries have an AA of 7 days or more.

Whereas mild head injuries may have a

momentary RA or none at all, more severe

head injuries may have an RA of days, weeks,

or months.

Patients recovering from more severe brain injuries with loss of consciousness usually go through

several variable stages:

• A period of coma.

• A period of agitation, restlessness, overreaction to stimuli, combativeness, and rambling

incoherent speech. Hallucinations may be

present. This stage varies widely in incidence and intensity. It may not appear at all

or may last up to several weeks.59

• A stage in which behavior is organized rather

than random, and the patient is responsive

to questions. There may be features of both

the amnestic confabulatory state and the

syndromes of denial, with anterograde and

retrograde amnesia, confabulation, environmental and temporal disorientation, reduplicative misidentifications and delusions,

and mood changes. Components vary in

duration but may last for weeks and months

and the patient later may be amnesic for

much of the period. While there are deficits

in memory and other forms of cognition,

and in attention and perception, the behavior also has positive, symbolic, and adaptive

aspects.

Post-Traumatic Amnesia

Anterograde amnesia (AA) is the period of time

following the traumatic event or interruption of

consciousness during which the patient is unable to

retain new information and for which he later has

no recall. Retrograde amnesia (RA) is the span of

time prior to the injury that the patient does not

recall. While post-traumatic amnesia (PTA) usually

MODERATE AND SEVERE HEAD INJURY
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Behavioral Consequences of Traumatic Brain Injury

has anterograde and retrograde components, these

may be dissociated and may have different mechanisms.60,61 The length of the AA is a good indication

of the severity of the brain injury but the extent of

the RA is much more variable. A study of a group

of soldiers with severe head injuries admitted to

Walter Reed Army Medical Center showed that

while some patients had extensive RA reaching

back for years with no recollection of having served

in the U.S. Army, others with comparable injuries

had RA of days or weeks.62 It is important to note

that the events took place at a time when the patient’s

brain was functioning normally, while those of

the AA occurred while he still had not attained

full consciousness. The duration of the AA roughly corresponds to the period of time over which

the patient was unconscious, confused, or disoriented. When interviewed later, patients are apt to

estimate the length of the AA in terms of when they

“woke up.”

It may be difficult to precisely determine the

duration of an RA from the patient’s verbal report.

For example, a patient may state that he remembers

nothing since embarking on a trip days or weeks

prior to his injury. On further questioning it turns

out that he does not know the destination or purpose of the trip, even though it had long been

planned. Some patients have a temporal gradient in

accordance with Ribot’s law, which states that

memories more remote in time are spared. There

are, however, many patients who do not show a

temporal gradient.61,63

AA and RA differ in respects other than their

temporal relationship to the traumatic event. Patients are likely to be unaware of an RA but may

complain about their inability to retain information. The time span of the AA tends to remain fixed

in terms of later recall, while the RA, on the other

hand, shrinks in the course of clinical recovery so

that eventually it covers only the seconds, minutes,

or hours immediately preceding the traumatic event

or loss of consciousness. While the moments preceding the loss of consciousness are irretrievable,

earlier events may sometimes be recovered under

hypnosis.64 Interestingly, functional amnesias and

fugue states not associated with brain damage are

wholly retrograde.

RA involves more than memory loss per se in that

it may be associated with feelings of unreality.

Patients may not believe that they were actually in

an accident, despite having been told about it many

times, and despite the evidence of a cast on a leg or

side rails on the bed. Some patients demand to see

a photograph of the wrecked car, and even then

may claim it is a different car. A soldier wounded

in combat in Korea refused a Purple Heart, stating

that if he had been wounded he would know it.

Even after patients acknowledge that they have

been injured, they may preface their answers to

questions of what happened with “I don’t know,” “I

don’t remember,” and “They say that...” There may

be jamais vu experiences. A soldier returning home

on leave said that he felt he had never been there

before. Another complained that the old songs he

knew were not familiar anymore.

Amnesic patients may have implicit knowledge

of events that they cannot consciously recall. Performance may improve with successive trials on

tasks that the patient may not recall having done

previously. Soldiers who could not remember having been in the service retained knowledge of military protocol, and men who could not remember

having been married could still recognize their

wives. In one such case the patient commented that

he knew his wife from their courtship days.

Amnesia can have positive as well as negative

aspects in that the patient’s last memory prior to

“waking up” or “coming to himself” in the hospital

may be a symbolic representation of current experiences and problems. Thus, the last memory of a

patient with severe visual loss was of getting a new

lens for his camera a few months before his injury.

Such last memories may be veridical, actual events

displaced in space and time, or confabulations. As

new problems develop in the course of recovery, so

may new last memories appear. A characteristic

“last memory” occurs in patients who have been in

an accident that resulted in fatalities. This has to do

with sleep or other loss of consciousness; going to

bed the night before, napping in the back seat of the

car, or passing out at drill a few days previously.

Over the period in which such memories are recalled, the patient usually expresses no conscious

awareness that someone has been killed.65

Anosognosia

Anosognosia—literally lack of knowledge of disease—is closely related to amnesia as patients deny

that they were injured or were in an accident. They

may also disclaim such disabilities as hemiplegia,

blindness, paraplegia, loss of a limb, facial disfigurement, and a craniotomy or tracheostomy. Patients may flatly deny that they are disabled in any

way, or minimize impairment by attributing a

paretic limb to a sprained ankle or “laziness.” Some

acknowledge the disability but regard it as outside

of the self, referring to it as an animate or inanimate
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object or in the third syntactical person as “he,”

“she,” or “it.” They may claim that the accident

happened to another person and do not get upset

when their erroneous statements are challenged.

Some claim that their disability was caused by rough

handling by the hospital staff.66 Many anosognosic

patients, like amnesics, may appear quite normal on

casual examination. Denial may also be expressed

in the form of joking and punning and caricaturing

disabilities.

As in amnesia, patients may indicate implicit

knowledge of their problems and traumatic experiences, as in the case of a woman who denied that she

had had a craniotomy but who complained of the

“sawing and hammering” on her head. Selectiveness is another indication of awareness at a lessthan-conscious level. Patients are not delusional or

confabulatory about a part of the body that is not

disabled in some fashion. Denial of physical disabilities usually clears within weeks, but denial of

memory loss and other cognitive impairments may

endure for months and years.

Laterality plays little role in the amnestic

confabulatory state, which appears most prominently after bilateral orbitofrontal, anterior temporal, paralimbic, and diencephalic damage. Anosognosia occurs more frequently after right hemisphere

lesions than after those of the left hemisphere. Such

pathology is usually extensive and involves more

than one lobe. In anosognosia for hemiplegia there

is usually both frontal and parietal lobe damage.

Patients with left hemisphere pathology may deny

their aphasia, which is usually of a fluent type, often

with jargon. Denial of memory loss is a feature of

frontal and diencephalic amnesias in which the

brain damage is bilateral.

Confabulation

Confabulations are defined as fictitious narratives without intent to deceive, or distorted versions of actual events. Some are spontaneous, fantastic, and unrelated to the person’s experience, but

most confabulations after brain injury are elicited in

response to questions about the patient’s disability

and reason for coming to the hospital. A study of

100 moderately and severely head-injured patients

seen at Walter Reed Army Medical Center found

that 60 confabulated at some time during their hospital stay.67 Initially confabulations tend to be brief,

multiple, contradictory, and transient, but, after the

stage of agitation, a patient may maintain a confabulation for weeks and months. Some, particularly early ones, are confabulations of exigency, as

in the instance of a patient with his arms restrained

who claimed that he had been shot in the hands.

Others are amplifications of denial, as in the case of

the man who explained his hemiparesis by stating

he had sprained his ankle in a football game. Other

confabulations are not associated with explicit denial, but are dramatizations, or allegorical or metaphorical representations of the patient’s problems

and disabilities. Although ostensibly referring to

past events, they may symbolize the patient’s current situation. The following is illustrative.

Case Study 1: Confabulation Following TBI

A 42-year-old field-grade supply officer sustained a

head injury in Korea when his jeep overturned. He was left

with slight weakness of his right upper extremity, and mild

dysphasia, dyslexia, and dysgraphia. He was seen at

Walter Reed Army Medical Center 4 months after his

accident. When asked what had happened to him, he gave

the following story, to be repeated on many occasions:

I had a big job overseas. I was an intelligence

officer for the Air Force. The man I replaced was a

captain and his assistant a first lieutenant so that

the two of them were working with me. I was sent

to check on their security. They were just as

Commie as if painted with a red brush. I had to write

out everything I found so that it could be read in

court in a court-martial for these men some day. I

wrote it out and turned it into headquarters. I had

enough written so that any jury in the right senses

would give these guys 40 years in jail right away;

they were just that Commie....68(pp386–387)

Comment: The repeated reference to reading, writing,

and right senses and to intelligence indicate the patient’s

knowledge of his impairments, not otherwise expressed.

The case also helps explain why patients may include

apparently circumstantial and irrelevant details in their

narratives and repeat them in each telling.

A new confabulation or a change in the content of

an old one may indicate a new stressful experience.

In the case just described, the patient was refused

permission to visit his wife. He appeared angry but

said nothing, but the next day he included a detail

about threatening to shoot a man for giving food to

Communists.

The content of confabulations is determined by

several factors. One is the nature of the stress or

disability. A second involves popular topics in the

news such as Communism and space travel. A third

factor concerns those themes that in the patient’s

past experience have been significant elements in

patterns of social relatedness and important sources

of identity. The Walter Reed study67 showed that

more than one half of the confabulators referred to
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Behavioral Consequences of Traumatic Brain Injury

family members, real or fictitious. They stated that

a brother, child, or parent had been in the accident,

often sustaining an injury identical with the patient’s

own. Confabulations about work and occupation

were less frequent but were longer and more elaborate. Paratroopers injured in car accidents or fights

were apt to confabulate that they had been hurt

jumping and the inclusion of expressions like “had

a Mae West” lent verisimilitude to the story. Confabulations about sports and minor illnesses were

usually associated with denial of disability. Confabulations about great violence and death were

associated with more disturbed behavior and somatic symptomatology.

As in amnesia and denial, patients may show

implicit knowledge of the disability or traumatic

event. This may appear in the content of the confabulation, as in the case of a soldier with a

tracheostomy who confabulated that he had been a

vocalist in a 17-piece band.68

In the course of clinical recovery, the content of

an erstwhile confabulation may be represented in

other forms of disturbed behavior. Following a

head injury sustained in a car accident, a soldier

confabulated about a girl passenger whom he said

he had saved from injury by shielding her head at

the moment of the impact. He was left with a left

homonymous hemianopia, and on his first leave

home, became extremely worried that a neighbor’s

child would go blind. He then became engaged to

a 15-year-old retarded girl in the hope that U.S.

Army doctors could operate and cure her.67

Environmental Disorientation

Disorientation for place or environmental disorientation takes on different forms depending on the

stage of recovery. During the period of agitation,

responses are random; the patient places himself at

work, in combat, in a bar. As his behavior improves, disorientation may appear in successive

patterns of misnaming, mislocation, condensation

of time and distance, and the confabulated journey.69,70 Patients usually say that they are in a

hospital but they give it the name of another hospital, real or fictitious, or use euphemisms like “place

for R and R,” “repair shop,” “retreat.” In misnaming,

the patient most often selects a hospital situated at

his training base or in his home town. The patient

may then name the hospital correctly but mislocate

it in places associated with work or home. Or, a

soldier may go on to name and locate the hospital

accurately, but greatly condense the distance or

travel time between the hospital and his home or

base. After a patient appears to have established

complete orientation, he may offer a confabulated

journey as in the case of a soldier who stated that he

had flown to Florida that morning.

Patients maintain their disorientation despite

cues, clues, and corrections. Even with the name of

the hospital in full view on bed linen, staff name

tags, and desk plaques, and, despite having been

told, patients refuse to accept the proper designation. The following case is illustrative.

Case Study 2: Environmental Disorientation

Following TBI

A 21-year-old soldier was admitted to Walter Reed

Army Medical Center after having sustained a head injury

and a traumatic amputation of his left arm in an automobile accident. His home was in Massachusetts and he had

been traveling to Washington from his station in Georgia.

He denied that he had lost an arm and stated that he was

in “Coolidge Memorial Hospital,” which he located in

Georgia. (It was later learned that the name was a

condensation of Cooley-Dickerson Hospital and the

Coolidge Memorial Bridge near his home.) Over the next

2 months, he successively located “Coolidge Memorial” in

North Carolina, Virginia, and Washington. Then it became “Walter Reed Memorial Hospital.” He gave up the

disorientation with apparent reluctance, “they say it’s

Walter Reed or something,” “it’s supposed to be Walter

Reed.” At the same time he admitted the loss of his arm.

Throughout the remainder of his 5-month hospital stay he

was oriented, but expressed a “feeling that there must be

a Coolidge Memorial Hospital somewhere.”66(pp46–47)

Comment: Enduring environmental disorientation is

not explicable in terms of confusion or overall memory

loss, but has positive motivational aspects. Here the

patient clung to his delusion in an apparent effort to

maintain identity.

Temporal Disorientation

Disorientation for date and time of day are associated with environmental disorientation and RA.

Patients displace backward in time and the greatest

displacements occur in patients with amnesia of

long duration.71 In disorientation for time of day,

the patient confuses morning and afternoon, and AM

and PM. He appears to gauge the time in terms of his

personal experiences and activities. No matter at

what time of day he was examined, one man usually

said it was 3 PM because that was when his wife

visited. Disorientation for time is particularly striking after a patient has been sleeping or dozing. A

man served with supper after awakening from an

afternoon nap was indignant over having been given

“spaghetti for breakfast.” Such temporal disorientation occurs even with a large wall clock in full
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view, and when the patient is permitted to look at

his watch. Nevertheless, such patients may be quite

capable of drawing a clock and putting the hands at

a designated time. Similarly, in disorientation for

date, a patient may persist in his misdesignation

even after being told or shown the correct date.

Disorientation for person will be considered under

the reduplicative disorders.

Reduplication

Reduplicative delusions and misidentifications

occur in a number of modalities; those of place and

person, time and event, objects, parts of the body,

and the self. One form is usually associated with

another. Like anosognosia and environmental disorientation, right hemisphere lesions are more common than those on the left even though both sides of

the brain are usually involved.

Environmental reduplication or reduplication of

place is the belief that there are two or more places

of the same name although only one actually exists.

The first case, in a woman with senile dementia, was

described by Arnold Pick in 1903 under the designation, reduplicative paramnesia.72 Henry Head73

reported the case of a British soldier in World War

I who, after sustaining a frontal missile wound,

thought that there were two towns of Boulogne in

France—one that he traversed on his way to the

front, and the other through which he passed on his

way home to England on leave. Head remarked

that the man appeared rational in all other respects

except that he wrote letters to his mother even

though he knew that she had been dead for years.

Reduplication of person is the belief that a person

has more than one identity. A soldier may believe

that a corpsman is also a cook in his unit. In the

syndrome of Capgras, which is not infrequent after

head injuries,74–77 the patient believes that a familiar

person, usually a close relative, is an impostor.

Another form of personal reduplication is the belief

that one has an “extra” child.

Temporal reduplication is the belief that a current event has also occurred in the past, an enduring

déjà vu experience. Patients hospitalized for a car

accident state that they have been in several recent

automobile accidents, or that they have previously

been treated at the hospital for the same condition.

It may be difficult to separate temporal from personal reduplication, as in an instance in which a

patient claimed that a nurse was a high school

classmate.

Patients may reduplicate both inanimate and

animate objects, as in claims that personal possessions and domestic pets have been replaced by

facsimiles. In reduplication of parts of the body, a

patient believes that he has more than two arms,

two legs, or one head. Reduplication of the self

involves the belief that one’s self is elsewhere or

that one has a double.

The incidence of reduplicative phenomena in

head injury varies with the method of study. Patients may not offer their beliefs unless specifically

asked, and some do not volunteer them because

they recognize their unusual nature. In the Walter

Reed study67 reduplication was found in 85% of

patients, excluding those who were markedly

aphasic or severely withdrawn. Reduplication is

commonly associated with retrograde amnesia, confabulation, denial, and environmental and temporal disorientation, or it may first be noted after these

conditions have improved or cleared. In one case a

patient originally mislocated Walter Reed in Texas,

his home state, then claimed that there were two

Walter Reed hospitals, one in Texas, and one in

Washington. Feelings of unreality and depersonalization often precede and are associated with reduplication. As noted, patients may not believe that

they were really injured, or that people are who

they say they are. In some instances, reduplication

does not appear until weeks, months, and even

years after the injury.

The two or more places, persons, events, objects,

and parts of the body, although alike in many respects, are not identical. They differ in some way

germane to the patient’s experiences, feelings, and

problems. For example, a patient admitted for

multiple injuries thought that there were three

Walter Reed Hospitals, one for head injuries, one

for fractures, and one for plastic surgery. Aggrieved

patients may believe that the nurses in the “other”

hospital were kinder and more considerate. A patient

with a draining suboccipital craniotomy wound

complained of “bad drainage” from one of his heads,

but claimed that his “other” heads were functioning

well.66 Alexander, Stuss, and Benson75 studied a

man who for several years after his head injury

claimed that his family had been replaced by another almost identical one. The only difference was

that the children of the “first” family were about a

year younger than those of the “second” family.

This difference appears to correspond with the period over which the patient estimated he had been

disabled. The authors noted that the patient recognized the implausibility of his story while maintaining its correctness. He behaved in his usual

manner toward his wife, showing neither anger nor

distress at her putative desertion. With the break-
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Behavioral Consequences of Traumatic Brain Injury

down in the unities of time and space, the “extra”

person becomes a condensed symbolic representation, a reification or personification of the patient’s

own experience.

The delayed onset of reduplication and its relationship to depersonalization and derealization is

well shown in a case reported by Staton, Brumback,

and Wilson.76 The patient had had a car accident at

the age of 23 followed by a week of coma. He made

what was apparently a good immediate recovery

but several months later had episodes of irritability

and complaints of memory difficulties. In the first

few months after his accident he experienced feelings of unreality but did not report them until 4

years later. At that time he expressed the conviction

that all of his current experiences had happened

before. When examined by Staton et al 8 years after

his accident, he described living in a world of fantasy in which his relatives were not the people he

had known but were slightly different “look-alikes”

or “doubles.” The family farm was a false duplication because recent buildings looked like they should

not have been built. Even his cat was not real

because of a scar on its ear. He denied that he could

be his real self because he was missing a tooth and

wasn’t working. He believed that the entire 8-year

period of disability and unreality lived since the

accident had occurred at some time in the past and

resulted in complete recovery.

Reduplication and accompanying phenomena are

adaptive in that patients expressing them are often

less agitated and disturbed than they had been

previously. Reduplication and confabulation combat feelings of unreality and nothingness, and the

reification of an experience in terms of a place,

person, or event may make it more “real” in the

sense that metaphor may make reality more vivid.

The validity of the denial and other symbolic representations of the patient’s problem is reinforced by

the way the content of the delusion identifies him

with such significant values as home, family, work,

health, and survival. Moreover, the delusion brings

certainty, order, and unity to what would otherwise

be masses of disparate, confusing, and contradictory data.

Mood Disorders

In general, the most conspicuous mood changes

occur in patients in whom there is a relative paucity

of verbal adaptive mechanisms. Patients with explicit denial tend to be bland and unconcerned,

sometimes euphoric and witty. Those with partial

denial might admit problems but attribute them to

the inefficiency or malice of the staff. Patients

without denial may be withdrawn and depressed,

making references to being in a prison camp or

cemetery, and such behavior may be punctuated

by episodes of agitation. Others are hypomanic

and ludic—a term introduced by Jean Piaget to

describe the play and imitative aspects of the

behavior of young children. These patients clown

and joke, and caricature their disabilities. In their

melodramatic presentations comic and tragic aspects are intermingled.78 Altered sexual behavior is

not uncommon, with lewd remarks, verbal and

physical advances to staff, and confabulations of

sexual activity. Aggressive and violent behavior

may appear, often as a withdrawal manifestation,

analogous to alcohol withdrawal, in patients

who recover full consciousness rapidly and must

face a new environment without going through a

stage of denial and other adaptive coping mechanisms. As in anosognosia and reduplications, lesions are more likely to involve the right than the

left hemisphere.

NEUROPSYCHOLOGICAL ASSESSMENT

Neuropsychological testing covers the areas of

attention, memory, language, calculation, constructional and visuospatial skills, praxis, abstraction,

and executive functions. It should be borne in

mind that these categories are, in some degree,

abstractions in the mind of the examiner rather than

models of the organization of the brain. A single

test may tap a number of functions. Clock drawing with the placing of the hands to a designated

time, for example, requires attention, visuospatial,

and constructional skills, and the ability to recognize that a 5 in one context means 25 minutes after

the hour, and that in another it indicates the hour

itself.

Formal neuropsychological testing is not performed during the first few weeks postinjury, because of impairments in attention, concentration,

and inhibition, and because changes in the perception of reality do not lend themselves readily to

tests for neural deficits. There are, however, a

number of measures that can be used with the

disoriented patient. The Galveston Orientation and

Amnesia Test (GOAT) documents the disorientation, and estimates the duration and severity of the
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PTA.79 Patients are asked for the last event they

remember before the injury, and for the first thing

they can remember after it. Other tests that make

minimal demands on the patient are tasks of reaction time, object naming, verbal fluency, and letter

cancellation. The patient’s ability to spell the word

WORLD forward and backward and state how many

nickels there are in a dollar and how many dollars

there are in 60 nickels is a valuable index of cortical

function. These measures can aid the investigator

in establishing the recovery slope and determining

when more extensive neuropsychological testing

can be accomplished.

Attention

Two types of attention are recognized. A tonic

form refers to the level of vigilance regulating overall information processing capacity. The second is

a vector function, which regulates the direction and

target of attention in any one behaviorally relevant

area or space. Tonic attention is related to the

activity of the reticular activating system. Directed,

selective attention is associated more with neocortical activity. Marked disturbances of tonic attention are found in the acute confusional states in

which the patient is highly distractible and cannot

maintain vigilance, is unable to pursue coherent

thought, and is unable to carry out a sequence of

goal-directed movements. Impairment of focal directed attention is found in hemineglect in which a

patient ignores or is unaware of one side of his

body, or one half of circumambient space, or both.

It occurs mainly with right hemisphere lesions involving the parietal and frontal multimodal association areas and their limbic, reticular, and sensorimotor connections.80,81

Overall attention can be tested by measuring

digit span. The examiner orally presents a string of

digits to the patient at a rate of one per second, and

asks him to repeat the list forward and then backward. A normal digit span forward is five to seven

items, and in reverse it is two digits less.81,82 Sustained concentration can be evaluated by the “A”

test in which the examiner reads aloud a list of 60

letters at a rate of one per second and the patient

signs by raising his hand when he hears the letter

“A.” Normal persons perform error free while

patients with deficits in attention tend to make

errors of omission. The tendency of patients with

impaired attention to have difficulty in inhibiting

responses can be evaluated with a “go-no-go” paradigm. The patient is asked to raise his index finger

when he hears a single tap and to make no response

to two taps, which the examiner makes by hitting

the undersurface of the table out of the patient’s

vision. In the Stroop interference procedure the

patient is presented with color words, each printed

in a color other than that spelled by the letters. The

task is to give only the color and to inhibit the

tendency to read the literal spelling.

Hemineglect has perceptual, motor, and motivational components. In drawing a clock the patient

may omit the numbers on one side or in representing a daisy he may similarly leave off the petals on

one side. Drawing of a human figure may show

only one arm, leg, eye, and ear. The patient reads

the word BRAKE as RAKE, or in the instance of

right-sided hemineglect reads HERON as HERO.

Writing may be confined to one side of a page. If

the patient is asked to bisect a horizontal line he is

likely to draw the vertical line on the side of the

midline ipsilateral to the lesion. When both sides of

the body are touched simultaneously the patient

reports only the stimulus on the intact side, although a single stimulus on the affected side can be

perceived, a phenomenon known as extinction. If

the patient is asked to raise both arms aloft he may

lift only one extremity, even though the other one is

not weak and he uses it in other activities. On a

letter cancellation task, performance in the detection of targets on the involved side may be improved by offering a reward.

Memory

There are various types and classifications of

memory and memory loss. These include the

amnesias; immediate, short-term and long-term

memory; recent and remote memory; verbal and

nonverbal memory; modality specific (visual, auditory, olfactory), episodic (autobiographical, specific events in time and space), semantic, and procedural (facts, procedures, skills) memory; and

memory for geographical places, for people, and for

animals. Testing therefore can be highly specialized.

Because of such specialization amnesics may do

well on many recall tests, especially if they are

allowed to rehearse silently. Rehearsal can be prevented by the Brown-Peterson interference technique, based on the known sensitivity of patients

with AA to distraction. The patient is presented

with trigrams or groups of 3 words over varying

intervals, and asked to count backward aloud during the intervals. Performance is far inferior to that

which would be accomplished had rehearsal been

permitted. The Famous Faces test in RA is based on
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Behavioral Consequences of Traumatic Brain Injury

the concept of a temporal gradient. The patient is

asked to recognize the faces of people prominent in

the news over periods in the past, and scores for

different decades compared. However, because

autobiographical memory can be profoundly impaired while knowledge of famous people and

events is spared83 and a considerable number of

patients do not manifest temporal gradients, the

test is of limited clinical value.

Story recall is routinely used. The patient is

asked to recall a 6-item passage such as “St Joseph’s

School burned down and 3 firemen were overcome

by smoke” immediately and after an interval of 5

minutes. Nonverbal memory can be evaluated by

having the patient watch the examiner conceal several of his personal possessions, and find them 5 to

10 minutes later. A more complex evaluation of

verbal memory can be done through the Rey Auditory Verbal Learning Test. The Rey-Osterrieth Figure Test provides a quantitative measure of nonverbal learning and memory.84

Language

Evaluation of language functions mainly concerns aphasia. Patients are tested from the standpoints of fluency of conversational speech, comprehension, repetition, reading and writing, object

naming, and word-word relationships. Note should

also be taken of handedness.

Nonfluent aphasia is characterized by sparse

verbal output (less than 50 words/min), effortful

speech, short phrase length, sometimes a single

word, poor articulation of speech sounds, and

dysprosody, the loss of melodic quality.85 Agrammatism, the omitting of function words such as

“and” and “to,” and of syntactic indicators such as

verb tenses and plurals, may be a feature. Fluent

aphasia, on the other hand, involves a normal or

excessive production of words, normal phrase

length, and intact articulation and prosody. There

may be paraphasic word errors, and jargon, the use

of neologisms or standard English words given in

meaningless or inappropriate contexts. Nonfluent

aphasias occur with lesions of the anterior dominant, usually the left, hemisphere while fluent

aphasias are found with more posterior lesions.

Comprehension is tested by having the patient

follow commands: Point to the window, Clap and

clasp hands, Stand up and walk to the door. If

severely impaired or apraxic he can be asked questions such as, “How many wheels are there on a

bicycle?” or asked to give yes or no answers to

questions such as, “Are the lights on in this room?”

or “Did George Washington have a beard?” The

patient may be asked to decipher passive sentence

structures such as “The lion was killed by the tiger;

which animal is dead?” Comprehension can be

impaired by lesions of both anterior and posterior

parts of the left hemisphere.

Repetition can be tested by having the patient

repeat words, phrases, and sentences. Aphasic

patients generally have more difficulty in repeating

passages with function words such as “no ifs, ands,

or buts” than they do with phrases containing content words such as “correspondents write frequently.” Failure of repetition is a cardinal feature

of conduction aphasia produced by lesions of the

perisylvian area.

Reading should be assessed both by reading aloud

and testing comprehension. While alexia without

agraphia is a reliable sign of a posterior left hemisphere lesion, alexia and agraphia may occur with

lesions at various points in the hemisphere.

Writing can be evaluated by asking the patient to

write his name, and take down a dictated sentence.

Note is made of word accuracy, spelling, and calligraphy. Disorders of writing are common in confusional states and are of limited value in localization.

The patient is asked to name common objects and

movements or pictures of them, along with colors.

Items that are most apt to yield errors are those that

are parts of wholes, such as a button hole, cuff, or

lapel, or have compound names such as doorknob

or coathanger. Color anomia may occur in association with alexia without agraphia. Generally,

aphasic naming errors are not of value in localization. Nonaphasic naming errors may also occur

with lesions of the right hemisphere and with bilateral damage. These are apt to involve items connected with the patient’s disability or that have

other personal significance for him, as in referring

to a wheelchair as “a director’s chair” or a plastic

drinking straw as a “cigarette.”86

Calculation

In testing a patient’s ability to add, subtract,

multiply, and divide it must first be determined

that he can comprehend the concept of an arithmetical operation, and that he is attentive to the task.

Serial subtractions of 7s is a useful test that depends

not only on calculation skills but on attention. Normal persons may make errors in the unit column, so

that the significant mistakes are in the tens column

such as “93, 76 ...” or “93, 86, 79, 82.” Tests of

addition and subtraction should involve carrying,

and in evaluating multiplication, rote tables should
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be avoided. The finding of dyscalculia is not of

great localizing value but the combination with

agraphia, difficulty in identifying and naming fingers, and left right disorientation is highly suggestive of a lesion in the left parietal lobe.

Constructional and Visuospatial Skills

These are tested by drawing and making designs.

The patient is asked to draw a clock, house, or cube,

or copy a complex design like the Rey-Osterrieth

Figure. In the block design subtest of the Wechsler

Adult Intelligence Scale, the patient arranges a group

of colored blocks in a design shown on a card.

Impairment occurs with lesions of either hemisphere. Evidence of hemineglect may also be found

in the drawings of patients with right hemisphere

lesions. Topographical orientation and memory

can be tested by having the patient draw a map of

his quarters or describe a familiar route. Impairment occurs with both bilateral and unilateral posterior brain lesions, the latter located more frequently in the right hemisphere.

Praxis

Apraxia is the inability to carry out a skilled

movement on command or in imitation even though

the person understands the task and there is no

primary motor disability. Ideomotor apraxia is the

inability to perform an act, such as a salute, although the patient can do it spontaneously. Ideational apraxia refers to the failure to carry out a

sequence of actions, such as folding a letter, putting

it in an envelope, and sealing it. The ability to

pantomime may also be tested by asking the patient

to pretend to comb his hair, brush his teeth, cut with

scissors, and fire a pistol. An apraxic patient is apt

to substitute a body part for the object. He may run

his fingers through his hair, rub his index finger

against his teeth, use his index and middle fingers

as scissor blades, and point his index finger and say

“boom, boom.” Serial hand movements can be

tested by having the patient assume three consecutive hand postures, first in a fist position with the

knuckle downward, then with hand open and palm

down, and then with hand open and edge down

while saying the positions aloud, “fist, slap, cut.”

Ideomotor apraxia is often associated with aphasia,

but other forms are difficult to localize. Interestingly,

apraxic patients rarely complain of any difficulty.

Dressing apraxia is the failure of a person to put

on a coat or a pair of trousers after the garments are

handed to him. He may get the sleeves reversed or

even try to put both legs into the same trouser. It is

considered to be a constructional difficulty rather

than a true apraxia. It may occur with right parietal

lesions along with topographical disorientation and

hemineglect, and is common in dementia and confusional states.

Abstraction

Abstraction is the derivation of a common principle or category from diverse elements. In the

Similarities subtest of the Wechsler Adult Intelligence Scale, the patient is asked how such items as

a chair and a table, or a cup and a saucer are alike.

Aphasic difficulties and loss of inhibition may contribute to failures as in the statement that “You

drink from a cup.” Proverb interpretation is commonly used, but has the disadvantage that most

proverbs are overlearned and do not require abstract thinking. Nonverbal categories can be tested

by asking the patient to sort out stimuli on the basis

of color, shape, or size. Impaired abstraction is

traditionally associated with frontal lobe lesions,

but may be a feature of more widespread brain

involvement.

Executive Functions

Defects in executive functions are characterized

by inability to plan and organize behavior and set

priorities among competing tasks. Such a patient

may do well on a large battery of neuropsychological

tests including those of memory, abstraction, and

reasoning.87–89 He might answer a test question of

what he would do if he found a stamped and addressed envelope on the street, but act quite differently. Testing should approximate real life situations. Loss of executive functions with preservation

of other faculties is a reliable indicator of focal

frontal lobe damage.

The long-term sequelae of TBI cover a broad

range of cognitive, affective, and personality

changes. While some patients show striking changes

in language, perception, and visuospatial processing, the more typical picture emphasizes

disturbances in memory, attention, personality,

LONG-TERM SEQUELAE
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Behavioral Consequences of Traumatic Brain Injury

and the cognitive and affective aspects of social

behavior.

Cognitive Changes

Memory problems include a deficit in the explicit

retrieval of new information (AA), and a much

more modest and variable RA. Immediate recall

and older memories are generally intact as are implicit memory processes. The deficit thus appears

to be primarily in the consolidation of new episodic

memory. These memory problems may be accompanied by slowed reaction times and reduced information processing skills, attentional deficits, and

impaired ability to divide cognitive resources. Related to this may be a deficit in concept formation

with difficulty in changing set, manifested by

perseveration on such tasks as the Wisconsin Card

Sort Test.

The follow-up study of head-injured Vietnam

veterans showed that damage to the basal forebrain

(BFB) in the proximal orbitofrontal lobe made

a large contribution to the episodic memory loss

as well as to the slowed reaction time and attentional deficits. BFB-injured men differed from

their non-BFB-injured matches only in having a

longer loss of consciousness postinjury, more episodic memory deficits and poorer performance in

the Wisconsin Card Sort Test.90,91 The basal forebrain lesions alone, however, were not sufficient to

produce dementia as suggested by studies of

Alzheimer’s disease.

In addition to residuals of aphasia, there are

nonaphasic disturbances of language that are more

difficult to classify. These include tangential and

fragmented speech, loose connections between

words and ideas, cryptic expressions, and a tendency for the patient to refer to himself and his

experiences in the third person. Thus, he may

describe his injuries as if they had happened to

someone else.62,92,93 These nonaphasic language disorders are mentioned not because they appear in a

majority of patients but because they may be mistaken for schizophrenic phenomena.

Affective Disorders

These depend only partly on the severity of the

brain injury and the location of the lesion. The

disorders are also influenced by associated verbal

behavior, premorbid experience, and by environmental events. Efforts to localize individual mood

states have led to variable, sometimes contradictory, results.

Anxiety

Anxiety has traditionally been regarded as a reflection of the patient’s efforts to cope with his

deficits and the social limitations imposed by them.

Extreme degrees of anxiety are expressed in the

catastrophic reaction, a term introduced by Kurt

Goldstein94 to describe the behavior of brain-injured German veterans of World War I. It consisted

of outbursts of frustration and emotional distress

experienced by the patient confronted by a task or

situation beyond his capabilities. Catastrophic reactions occur predominantly in patients with left

hemisphere lesions, especially those situated anteriorly, and associated with nonfluent aphasia. A

study of Vietnam veterans seen 15 years after injury

showed, however, that feelings of anxiety and “edginess” were experienced most frequently by men

with right orbitofrontal damage, while feelings of

anger/hostility were most frequent after left

dorsofrontal lesions. Generally, patients with

orbitofrontal lesions appeared more affectively

blunted and hostile than any other lesion group or

controls.2 The study also showed that cognitive deficits played a lesser role in right hemisphere mood

change than they did in left hemisphere lesions.

Some forms of anxiety disorder have been

related to serotonin excess95 or excessive neuroadrenergic activity.96 Other neurotransmitter systems including γ-aminobutyric acid (GABA) have

also been implicated in anxiety disorders.96

Denial or Unawareness

While anosognosia for physical defects such as

hemiplegia usually clears within 2 or 3 months,

denial or unawareness of cognitive and other behavioral disabilities may persist much longer. The

so-called anosognosic attitude, while it combats

anxiety and depression, may lead to a number of

undesirable consequences. The patient may blame

his problems in social relationships on weakness or

an unsteady gait. He may have unrealistic work

expectations, and be unwilling to accept a job that

he feels is beneath his capabilities. He may see no

need for training or rehabilitation.

In the early stages when the anosognosia is complete and has the supporting cognitive framework

of confabulations and delusions, the patient is usually serene, but as brain function improves, he may

become anxious and depressed. He may develop

headaches and other somatic complaints. He may

become obsessively concerned with his own health

and that of others. He may express concern about
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336

minor facial blemishes or his teeth, and express

fears of falling or getting a haircut. Some patients

become preoccupied with God and sin and leading

a better life. Paradoxically, the patient becomes

more emotionally disturbed at a time when his

brain function is recovering.

Dealing with denial and the catastrophic reaction is a major task of neuropsychological rehabilitation, and unless these phenomena are dealt with,

improvement in psychosocial adjustment is much

less likely to occur.93 Awareness allows the patient

to experience a normal grief reaction and adjust to

lost skills and loss of status. On the other hand,

other patients with severe brain injuries remain

aware of their problems. A soldier who had returned to duty complained on follow-up that it was

difficult for him to make new friends because he

could not stop himself from talking so much.

Depression

Depression in the form of feelings of helplessness, unworthiness, guilt, reduced self-esteem, loss

of interest and initiative, and diminished libido is a

common later sequel and can appear at any time

postinjury. Depression is not directly related to the

severity of the brain injury or the degree of

neuropsychological impairment.93,97 The depression may not be a classical one, worse in the morning, and associated with weight loss and psychomotor agitation or retardation;98 however, the

classical symptom of insomnia is common. Social

withdrawal may be a feature of depression, but in

other instances it may be simply the avoidance of

coping with a stressful situation.93 Decreased sexual

drive and diminished erectile function may or may

not be associated with depression.99 While reduced

sexual drive along with cognitive loss, and physical

complaints like headache and fatigue are factors in

troubled domestic relationships, increased sexual

drive may also be a problem.

Location of the lesion is another determinant.

Major depressions are more common after left than

right hemisphere lesions, with the greatest frequency

following left frontal damage.100,101 Depression,

however, is also common with right hemisphere

pathology, especially in patients without denial

and the associated phenomena that have been described.93,102 The hemispheric asymmetry has been

attributed to differences in cognitive capacities of

the hemispheres, to the adaptive role of denial,

confabulation, and reduplication, and to direct biochemical effects. Some forms of depression appear

to be related to depletion of brain serotonin,103 and

it has been shown that after brain injury there is

increased serotonin receptor binding in intact areas

of the right hemisphere suggesting better biological

adaptation.104

Premorbid experience and the quality of

psychosocial functioning also play a role in depression following brain injury, and in later-onset depression these factors are of greater importance

than lesion location.105 A recent civilian study of

acute and late-onset depression after closed-head

injuries found that patients in both groups had

more psychiatric disorders and poorer social functioning than controls; but, while acute onset depression was significantly related to left anterior frontal

lobe localization, late onset depression was not

related to the site of brain damage.105

Secondary mania after TBI is far less common

than depression as a long-term sequelae. Case

reports indicate onsets of from weeks to years

postinjury with involvement of orbitofrontal and

basal temporal regions and other subcortical structures, and greater on the right side of the brain.106–108

Aggressive and Paranoid Behavior

Aggressive behavior may appear at any time

after a brain injury. Outbursts of temper with

verbal and physical aggression may be a response

to frustration, and be triggered by small amounts of

alcohol or other drugs. Violence in the sense of

directed physical force against persons or property

may occur when the patient feels that he is being

threatened or persecuted or will be harmed, and

also in the absence of paranoid delusions. Paranoid

attitudes may be expressed in justification of acts of

violence. When episodes of explosive rage are out

of proportion to any precipitating stimulus and

especially when they are followed by amnesia, they

raise the question of temporal lobe epilepsy. It is

likely, however, that the incidence of both posttraumatic temporal lobe epilepsy and directed

assaultive destructive behavior in epilepsy has been

exaggerated.109–112 More relevant considerations are

a history of severe combat stress, violence in civilian life, and the immediate environmental situation. While a history of head injury is very common

among patients who come to medical attention because of violence, the incidence of violence in controlled follow-up studies of patients with head injuries is far lower. A 5-year follow-up study of 1,830

Finnish veterans of World War II, 32 to 37 years

after the end of the war, who had sustained pen-
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Behavioral Consequences of Traumatic Brain Injury

etrating brain injuries did not show a higher frequency of violent crime than did nonwounded veterans. Nor was there more violent crime in men

with frontal or temporal lobe lesions.113

The Overt Aggression Scale114 grades a spectrum

of aggressive and violent behavior ranging from

verbal threats, curses, and insults to physically

destructive acts against objects, to physical harm

to the self, to physical aggression against other

persons.

Psychoses

Psychosis can be a late sequel of combat-incurred

brain injury recognized months, years, or decades

after the trauma. A review of the German literature

of the Franco-Prussian War of 1870 to 1871 by Adolf

Meyer115 noted that less than 1% of soldiers with

serious brain damage became insane, but the belief

that dementia praecox, catatonic psychoses, and

schizophrenia could be caused by brain trauma was

prevalent during and following World War I. Longterm follow-ups of American casualties of World

War II are not available, but a Soviet investigation

of 1,168 brain injured veterans reported a 9.8%

incidence of schizophrenia mainly of the depressive-paranoid and depressive types.116 It can be

pointed out that many diagnoses of schizophrenia

were made before standard classifications were established and before the delusional misidentification

reduplicative syndromes of organic origin and the

metabolic dementias were well known.

More recent studies, notably those of Finnish

veterans of the 1939 to 1944 wars with the Soviet

Union, have shown that brain trauma is not a significant cause of schizophrenia. In the Finnish

series, schizophrenic psychoses appeared more frequently in men who had had mild head injuries and

had not lost consciousness than in the more severely injured, and there was a larger proportion of

patients under the age of 20 at the time of the

wounding than there was in the 20- to 34-year-old

group.117 A British study118 found that while the

number of schizophrenic-like states following brain

damage exceeded that expected by chance, schizophreniform reactions were more frequent than process schizophrenia, and there was no increase in

genetic loading.

The most extensive and detailed investigations

of psychoses following combat-incurred brain injuries have been carried out at the Kauniala Hospital

for Disabled War Veterans in Finland where the

treatment and rehabilitation of all brain injuries

from World War II are centralized. Investigators

there have found a rising incidence of psychoses

over the past 40 years; rates of 4.4% in 1951, 8.9% in

1969, and 12% in 1993.117,119,120 A control group of

pneumonia patients in the most recent study had an

incidence of psychosis of 3.3%. The most frequent

diagnoses were paranoid delusional state, major

depression, epileptic psychoses consisting of confusional states after seizures, and organic psychosis

(dementia). Delusional psychoses lasted less than a

year in 28% of cases, and more than 5 years in 40%.

Jealousy and the fear of being sexually betrayed

constituted the most prominent delusional content.

The delayed onset of psychosis requires explanation. One aspect is that with the passage of time the

risk factors for further brain damage, such as

the use of alcohol and other drugs including

anticonvulsive medication, additional injuries, cerebral vascular impairment, and systemic disease,

increase. Second, the damaged brain is more sensitive to the effects of the stresses of living associated

with the person’s diminished capacities. Another

issue concerns the time that a psychotic reaction

becomes overt. As in the case reported by Staton et

al,75 feelings of unreality and reduplicative phenomena may long antedate the florid manifestations. Other studies have linked late onset psychoses with epilepsy, even though only a minority of

psychotic episodes are associated with seizures.121

TREATMENT

One of the most encouraging aspects of TBI rehabilitation is the amazing ability of the young adult

brain to compensate for many aspects of injury

naturally. Over the past 2 decades, however, it has

become apparent that most TBI patients will benefit

from some level of TBI-specific rehabilitation. The

field of TBI rehabilitation has grown exponentially

over this time, but the exact form and intensity of

rehabilitation indicated for a given patient remains

debatable.

Multiple therapeutic strategies, including coma

stimulation, reality orientation, cognitive therapy,

speech therapy, occupational therapy, recreation

therapy, and music therapy, have been applied to

the TBI patient. While selected elements of many

of these will undoubtedly prove useful in the
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TBI setting, there has been a paucity of scientific

validation for these often expensive interventions

(including comparison with minimal care, supportive models).

If progress is to be made in this area, rehabilitation modalities must be subject to the same scrutiny

for indications, dose, duration of treatment, and

efficacy as are other medical treatments, including

drugs. The ultimate goal of therapy should be the

independence and community reintegration of the

patient within his or her limits, rather than the

specialized treatment of specific deficits simply

because “they are there.”

All too often, scarce resources available to the

patient are used up in the early acute and postacute

phases on evaluation and therapy of deficits that

will improve anyway or that are relatively unimportant to the ultimate goal of independence. Some

programs may be actually counterproductive by

fostering continued dependence. Relatively costeffective interventions such as training in specific

community reintegration skills (eg, decision

making) and certain forms of behavioral modification may end up being omitted because the limited

funds available were used up in earlier, less relevant therapies.

Although cognitive rehabilitation has yet to

fulfill its promise by submission to careful group

and case-series analyses, the reality is that most

TBI patients will receive some form of cognitive

rehabilitation during their postinjury course. In

fact, some drug therapies may potentially be

most effective when used in conjunction with cognitive remediation programs. Thus, the possibility

of rehabilitation-drug interactions when evaluating drug effects on independent variables must

be addressed in pharmacological studies by, at

a minimum, categorizing the type, frequency,

and duration of remediation. More sophisticated

studies can adapt both therapy and agent as dependent factors.

Behavioral Management

The treatment of the behavioral consequences of

serious brain injuries varies with the stage of clinical recovery. During the initial acute stage of agitation, aiding orientation and cutting down on environmental diversity may be useful. After the initial

phase, it should be recognized that denial, amnesia,

confabulation, and reduplicative misidentifications

are “normal” phenomena and do not have the same

ominous significance of delusions in nontraumatic

mental illnesses. Barring abnormal neurological

signs and impairments from other injuries, patients

are usually discharged from the hospital after they

become oriented and able to retain new information. They are then reevaluated after a 6-month

period over which the greatest part of improvement

in cognitive functions occurs.

Caution should be exercised in sending patients with

a great deal of denial back to duty or accepting their

statements about their condition at face value. Patients

about to be discharged from the hospital or allowed

leave should be warned about the effects of alcohol,

indulgence in which is particularly apt to occur

after weeks of confinement. An apparently recovered patient may become disoriented and disturbed

after relatively small amounts of alcohol. In anticipating such situations, the Amytal Test described in

Chapter 15, Conversion Disorders, is useful. If a

patient becomes disoriented or confabulatory under the effects of barbiturates, then alcohol is apt to

produce a similar reaction.

While the major recovery of cognitive functions

takes place in the first 6 months, patients may continue to make progress in adapting to their deficits.

It is doubtful if cognitive retraining is of value in

that the damaged brain can relearn lost function,

but rehabilitative measures may improve behavior

and social skills. The aims of such therapy are to

provide the patient with the conceptual or analogical model of what has happened to him, help him to

recognize both his defects and remaining strengths,

train him in alternate strategies, and teach him how

to behave in social situations.92

Pharmacological Management

While behavioral rehabilitative measures are the

cornerstone of therapy, psychopharmacology has a

role in the management of symptoms. Drugs may

be indicated for the treatment of depression, agitation, violence, and psychoses, and for the control of

pain and seizures. Accounts of anticonvulsant

therapy are available in standard neurological texts,

and this section focuses on the treatment of disturbances of mood and behavior and of pain in the

brain-injured patient.

It must be pointed out that the use of drugs in the

control of behavioral changes, particularly agitation and aggression, is controversial and in some

situations such control is best achieved by

nonpharmacological intervention. Drugs may have

undesirable effects, and brain-damaged persons are

not only more sensitive to the actions of alcohol and
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Behavioral Consequences of Traumatic Brain Injury

personality disorders, mitral valve prolapse, peptic

ulcers (doxepin is a stronger histamine-2 blocker

than cimetidine), and some chronic pain disorders.122

The antidepressants of choice for chronic pain

appear to be those that affect noradrenergic

neurotransmission (imipramine, amitriptyline,

desipramine, doxepin, etc.) rather than those affecting serotonergic neurotransmission (fluoxetine,

sertraline, fluvoxamine, paroxetine, etc.). An exception to this generalization is fibromyalgia, which

appears to respond better to serotonergic drugs.

Because the tricyclic antidepressants (including

those affecting noradrenergic neurotransmission

given above) can lower seizure threshold, patients

with head injuries must be carefully assessed.

Furthermore, anticonvulsants (most notably

carbamazepine and phenytoin) can cause induction

of enzymes in the liver that rapidly detoxify tricyclic antidepressants (TCAs), making it difficult to

achieve therapeutic blood levels. Some patients

respond at dosages of TCAs that would be subtherapeutic for depression; however, many cases

require higher dosages. Despite prescribing difficulties, TCAs can give dramatic pain relief.

A report of cases of causalgia resulting from

missile and fragment wounds sustained in the fighting in Lebanon from 1975 to 1981 indicated marked

relief of pain with phenoxybenzamine, an α-1,2-

noradrenergic antagonist.123 The drug, however,

may be contraindicated in head injuries, as it has

been found experimentally to retard recovery following brain damage in animals.124

Pharmacotherapy of Mood and Behavior Disorders

Standard antidepressant and anxiolytic medications are usually efficacious for these conditions.

Anxiolytics, preferably less sedating ones, should

be used cautiously and usually briefly because of

their euphoriant and addictive potential. Because

the antidepressants, particularly those affecting

serotonergic neurotransmission, are effective

anxiolytics in chronic usage, a useful approach is to

start an antidepressant and anxiolytic together for

rapid control of anxiety then discontinue the

anxiolytic in a few weeks, after the latency period of

the antidepressant has ended.

Electroconvulsive therapy is particularly benign

compared to drug therapy for patients with various

medical conditions, and this applies as well to those

with TBI. Due to legal considerations, electroconvulsive therapy is often reserved for patients unresponsive to antidepressant therapy; however, this

barbiturates but to those of other drugs as well. Antidepressants, for example, have more sedative, disorienting, hypotensive, and anticholinergic effects than

in non-brain-injured patients. Neuroleptics such as

the phenothiazines and the butyrophenones may be

helpful in diminishing strong emotional outbursts,

but they also produce affective and cognitive deficits, lower seizure thresholds, and may actually

exacerbate aggressive behavior. These medications

may also increase the risk of abnormal involuntary

movements and parkinsonism acutely, and tardive

dyskinesia, tardive dystonia, and tardive akathisia

with chronic use.

In theory, cholinergic, noradrenergic, and dopaminergic drugs tend to activate or increase aggression in TBI patients, while serotonergic (fluoxetine,

trazodone) and GABA-ergic (benzodiazepines,

valproate) drugs tend to decrease it. In practice,

however, pharmacological management of symptoms

in a given individual remains largely empirical. The

choice of drug is also determined by the postinjury

stage. Whereas a neuroleptic like haloperidol may be

indicated for acute initial violent behavior, it is

contraindicated for later episodes of aggression in a

neurologically stable patient.

Pharmacotherapy of Pain

Pain as a direct result of brain tissue damage is

uncommon, but headaches are a complaint, and

pain may be a feature of associated injuries involving the spinal cord and peripheral nerves. Narcotic

analgesics are generally contraindicated in the treatment of chronic pain especially in patients with

impaired brain function, and combinations of nonsteroidal antiinflammatory drugs (NSAIDs) and

antidepressants are preferred.

Headaches are more apt to be a problem in later

stages when patients must face the stress of diminished capability and altered life style. Treatment is

much like that of non-brain-injured patients. In

headaches of a vascular type ß-adrenergic blockers

and antidepressants are often effective. Antidepressants have also been of benefit in headaches

caused by muscle contraction. Interestingly, depression rating scales may show little change in the

level of depression despite marked improvement in

headache control.

Antidepressants probably should be given a different name because they are useful in treating a

variety of other conditions including anxiety disorders, panic disorders, PTSD, obsessive-compulsive

disorders, bulimia and anorexia, phobic disorders,
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340

legal artifact should not prevent its use in cases

likely to respond.

If mania occurs, mood stabilizers such as lithium,

carbamazepine, or valproic acid may be used. Obviously, in mixed conditions (seizures plus mania,

depression plus anxiety, depression plus pain) a

single agent efficacious for both conditions may be

selected.

PTSD is a common sequela not only of psychological trauma but also of physical trauma. Its

treatment is described in Chapter 16, Chronic PostTraumatic Stress Disorders. In terms of the braininjured patient with PTSD, nonsedating agents are

preferred and if a seizure disorder coexists,

anticonvulsants (carbamazepine, clonazepam)

should be tried first. Because clonazepam has serotonergic activity, it may be helpful through a dual

mechanism.

Alcoholism, which is often associated with PTSD,

poses particular problems in patients with TBI because of the intermittent withdrawal from alcohol,

which is sometimes complicated by seizures. Fortunately, benzodiazepines used for withdrawal are

effective anticonvulsants.

Inasmuch as aggressive behavior may be modulated through changes in a number of neuroanatomic

sites and many neurotransmitter systems, including serotonin, norepinephrine, dopamine, acetylcholine, GABA and the opioids,125 a variety of medications including neuroleptics, anticonvulsants,

β-adrenergic blockers, benzodiazepines, and serotonergic agents (including lithium) may be useful in

chronic aggression.126 When aggression is severe or

dangerous, neuroleptics (phenothiazines, butyrophenones, etc.) may be initially required to gain

control. Neuroleptics may be helpful but the complications have been noted. Attempts should be

made to replace them with more benign and often

more efficacious medications such as mood stabilizers (lithium, carbamazepine, valproic acid,

clonazepam, and occasionally calcium channel

blockers).

β-adrenergic blocking agents (propranolol,

metoprolol, etc.) have been used for decreasing

aggression, particularly in patients with organic

brain syndromes127 and α-adrenergic blocking agents

(clonidine) for reducing disinhibited behaviors such

as sexual exposure, lewd remarks, etc. Serotonergic

agents (trazodone) and benzodiazepines (lorazepam,

clonazepam) have been found useful in some patients with chronic aggression.126 Usually, treatment requires experimentation with a variety of

medications until one that is efficacious is found.

Silver, Yudofsky, and Hales128 recommend the

use of propranolol in the management of the violent

patient, beginning with a 20 mg thrice daily schedule and increasing it by 60 mg/d every 3 days, while

monitoring blood pressure. They note that daily

doses above 800 mg are not usually required and

recommend that the patient should be maintained

for at least 8 weeks before concluding that the

medication is ineffective. In heavy smokers, atenolol

may be preferable because it tends to spare the

lungs; however, its latency period is longer than

propranolol.

Because of success in the treatment of attention

deficit and hyperactivity disorders, the use of

psychostimulant drugs such as methylphenidate

and amphetamine has been suggested for the management of the behavioral sequelae of TBI. Animal

studies have also indicated a possible role. Dopamine agonists have been found to attenuate or abolish the septal rage syndrome, which follows lesions

of the septal nuclei in rats.129 A single dose of δ-amphetamine given 24 hours after injury has been

reported as accelerating recovery of motor function

after unilateral sensorimotor and bilateral frontal

cortex ablation in rats and cats, an effect blocked by

haloperidol given 24 hours after surgery or by restraining the animals.130 These remarkable findings

in different functional areas offered hope that stimulation of catecholaminergic systems might facilitate

processes of cognitive and other behavioral recovery in TBI. To date, however, there is insufficient

evidence that psychostimulants can improve brain

function.

Individual case reports and anecdotal observations131–133 have indicated that psychostimulant

drugs may relieve tiredness, improve initiative and

concentration, promote feelings of well-being, and

result in better performance on some tests of memory

and attention. The one controlled study of a case

series, however, has yielded disappointing results.134

Methylphenidate was superior to placebo but there

was a marked discrepancy between subjective report and performance. Only a few objective measures showed clear stimulant effects, and there was

no coherent pattern to the measures that were responsive to the drug. Patients with mild and moderate head injuries with symptoms of impulsiveness, hyperactivity, distractibility, and emotional

lability may be given a trial of psychostimulants

under close supervision, with consideration of the

dangers of abuse, increased risk of seizures, withdrawal manifestations on cessation, and a psychotic

reaction.135
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Behavioral Consequences of Traumatic Brain Injury

OUTCOME

A surprisingly good overall outcome can be seen

in many young, moderately severely to severely

injured patients, a finding that probably reflects

compensation for lost functions more than recovery

of the injured tissue itself. Thus, “floating” or

dynamic endpoints can be identified in the post-TBI

course: recovery from coma, return of orientation,

resolution of post-traumatic amnesia, shrinking of

retrograde amnesia, number of significant deficits

identified on initial neuropsychological testing,

number of significant deficits identified on the last

neuropsychological evaluation, and the steepness

of the recovery slopes. Nevertheless, an important

milestone yet to be reached in the TBI field is the

development of reproducible, universally accepted

measures of function and long-term outcome with

which to compare the value of various interventions.1

Final outcome is a composite of a number of

elements, including preinjury, neurologic, cognitive, behavioral, and psychosocial function, all of

which may interact differently in each individual

patient. When evaluating efficacy of a given therapy

it is necessary to study all of these elements in the

context of outcome as a whole; any evaluation battery should thus include at least some measure of

each. It is misleading, for example, to use improvement in a particular overlearned memory task as a

measure of outcome. While there may not be any

ideal surrogate or summary measure for outcome,

return to gainful employment may be a useful one

in most TBI populations.

The second author has had the opportunity

to study the disabilities that affect return to work

in a large cohort (N=520) of head-injured Vietnam

veterans participating in the Vietnam Head

Injury Study. A 1-week, standardized, multi-disciplinary outcome evaluation was completed

on each of them. Some 15 years postinjury, 56%

of these men were gainfully employed, compared

to 82% of an uninjured Vietnam veteran control group.136 The occupational distribution of

those who were working was essentially no different from that of normal uninjured young American

males.137 After exclusion of severe aphasic and

triplegic patients, none of whom worked, a multistage statistical analysis of this data, including factor and multiple logistic regression analyses, identified seven specifically defined disabilities that

had a significant impact on return to work: posttraumatic epilepsy, hemiparesis, visual field loss,

verbal memory loss, visual memory loss, psychological problems, and violent behavior. Interestingly, these seven items were found to be relatively

equipotent, so that a simple sum of any of them

could yield a “disability score,” which predicted

return to work.

Patients were able to compensate relatively well

for up to any three impairments, but beyond that

there was a sharp drop in work rates. Other factors

contributing significantly to return to work included

preinjury intelligence, total brain volume loss on

CT scan, and education postinjury. This experience

is a further reminder of the importance of considering outcome from TBI as dependent on a set of

functional skills, rather than identifying one or two

disabilities as its principal determinant.

It is difficult to predict the long-term social outcome of individual brain injuries even though the

location and extent of the lesions are known. There

are, however, a number of useful observations. Men

whose injuries were sustained under particularly severe combat conditions, and those who have had a

prior head injury or a history of combat-induced

stress reactions, are apt to have more severe behavioral consequences. Injuries to other parts of the

body are a factor. A follow-up study of military

personnel treated at Walter Reed Army Medical Center for mainly closed-head injuries showed that paPREDICTABILITY AND PREDISPOSITION

tients who were violent in the acute stage and who

used language of violence with references to death,

blood, and mangling went on to have higher problem ratings on a scale based on employment record,

social sexual adjustment, somatic symptoms, and

emotional state than did men with less disturbed

initial behavior.138 Similar findings in civilian patients are reported.139 Alcohol consumption at the

time of injury is said to increase the severity and

duration of initial agitation and the amount of later

memory loss.140,141 Also, premorbid personality factors may play a role. The following case is illustrative.
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Case Study 3: Disastrous Social Consequences

of a Brain Injury

A 44-year-old infantry commanding officer sustained a

head injury and a fractured femur in a car accident while

on a training exercise. His wife, who was driving, and his

five children were also injured. On admission to the

hospital he responded only to painful stimuli, and, because of extreme agitation, was restrained over the next

10 days. After transfer to Walter Reed Army Medical

Center 6 weeks after injury, he was restless, overtalkative,

tangential, and suspicious. He spoke incessantly of his

children, and believed that one of them had been killed in

the accident. He accused the hospital of running a dope

ring and demanded an investigation.

In the first formal interview on the psychiatric ward he

appeared hypomanic. He was unsure of the date, mistaken about his age (giving his wife’s), and did not know

the name of the hospital beyond calling it “the best

hospital in the world.” When asked about his accident he

went into a lurid account of the consequences of nuclear

and biological warfare (the subject of his course) and

talked at length about his children. The RA was estimated

at one half hour and the AA later determined as having

endured for 7 to 10 days. His “last memory” was of

scolding his wife for not having arrived to pick him up in the

car. There was temporal reduplication; he stated that the

examiner had given him a mental examination at Fort

Benning, where the accident occurred. He admitted

having suffered a head injury and a broken leg, but denied

any memory loss or mental problems. He agreed that he

was emotionally overstimulated and attributed this to his

eagerness to see his family. He complained of blurred

vision on reading, and neurological examination disclosed

a partial internuclear ophthalmoplegia.

Orientation cleared over the next few days but the

temporal reduplication persisted. Following a carotid

angiogram, performed with some difficulty, he confabulated the next day that he had acted as defense counsel

for several soldiers convicted of rape and attempted

murder. He claimed that one of the men had been hanged

and described in vivid detail, indicating on himself, how

the man’s neck had been stretched at least 18 inches. He

also believed that he had been given electroconvulsive

therapy (ECT).

At the time of discharge from the hospital, 4 months

after his injury, the patient’s mood was subdued but he

would become overexuberant during testing and interviews. He was no longer confabulatory but believed that

a steel plate had been placed in his head. (A pin had been

inserted in his femur.) He also became preoccupied with

repairing the leaky roof of the buildings on his farm. He

had considered having this done prior to his injury, but had

given up the idea because of the great expense. Now,

however, he was determined to proceed regardless of

cost. Despite the recommendation that he not resume his

occupation as an agricultural administrator for several

months, he insisted on returning to work immediately.

Follow-up over a 5-year period revealed a pattern of

domestic and emotional difficulties. He became increasingly critical of his children and demanded perfection from

them. He also projected his concerns with his own health

upon them. He forbade them to watch television as it was

bad for their eyes (he had some residual blurred vision),

and would not allow his daughter to ride her horse for fear

of a head injury. He was sexually demanding, insisting on

intercourse several times a day, without any display of

affection. After his wife had a hysterectomy following a

hemorrhage, he accused her of evading her conjugal

duties. After one of his sons drank poison in a suicidal

gesture, he considered shooting himself in the head for

having failed as a parent. He was technically competent

on his job, but was overbearing with subordinates and

charged that his secretary was talking about him behind

his back. After 3 years his wife obtained a separation, and

he went to live with his widowed mother and to work for his

brother.

Some of the behavior was an exaggeration of premorbid

personality traits. The patient had grown up in a prosperous Calvinistic work ethic family, in which the rod was not

spared. His mother recalled him as a quiet, timid child

who might be punished by his father for showing fear.

His wife described him as a driving—and driven—

perfectionistic, stubborn person, proud of his success in

his several businesses and his military activities. He was

the dominant member of his family, very attentive to his

children and intent on making them responsible and

achieving. His wife noted that he never played with them.

He took pride in his good health, and regarded illness as

a sign of weakness of character. He was intolerant of the

ills of others, except in the case of his children, about

whose even minor ailments he would become excessively

worried; he was particularly unsympathetic with mental

illness. He had been sexually active, and had taken any

refusal by his wife as a personal rejection. Overall, he had

been concerned with the physical aspects of relationships

and situations with strong views of race and blood lines,

looks, smells, diet, and nutrition.

Comment: The following features are noteworthy.

• Preservation of technical competence with marked

disturbances in social and emotional behavior.

• Association of a long initial period of violence with

an unfavorable outcome.

• Confabulation about the hanging of a deserter as

a symbolic representation of the patient’s traumatic carotid angiogram.

• The “last memory” prior to the injury of scolding

his wife as symbolic of the patient’s habitual

hypercritical attitude toward her.

• The replacement of the patient’s initial preoccupations and delusions about his children with a

projection onto them of his own physical problems.

• A premorbid predisposition to denial and the role

of denial in the patient’s premature return to work.

• A possible connection between the patient’s

premorbid emphasis on the physical aspects of

personal relationships with later paranoid attitudes, including these expressed through sex.
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Behavioral Consequences of Traumatic Brain Injury

The mechanisms by which premorbid experience interacts with alterations in brain function

following TBI are poorly understood. Most clinicians are aware of a relationship but the lack of a

method of study has hampered research in the field.

There are so many theories of personality that selection of measuring instruments appropriate for brain

injuries is a problem.142 Patients are often not good

informants, and interviews carried out with relatives are of necessity retrospective. Another difficulty is that the life experience of a 17- or 18-yearold youth is so limited that his character cannot be

fully evaluated. Some writers believe that behavioral traits such as disorderliness, argumentiveness,

suspiciousness, and anxiousness become more pronounced and that extroverted patients become more

boisterous.97 However, disorderly patients may

previously have been orderly, and patients with

frontal lobe lesions may have deficits in executive

functions and the social proprieties regardless of

premorbid personality.

Another approach has been based on the idea

that premorbid experience influences the positive,

adaptive—or maladaptive—aspects of behavior

following brain injury, as opposed to such negative

symptoms as lack of empathy, loss of initiative,

impaired emotional recognition, and diminished

impulse control. Denial and some other delusions

and confabulations are adaptive in the sense that

they are attempts by the patient to cope with and

interpret what has happened to him, make sense

of his environment, and gain a feeling of reality.

Interviews with relatives are directed toward learning how the patient has reacted to stress in the

past, and toward determining the values through

which he has structured his social environment.

These values include attitudes toward health and

illness, work and efficiency, physical appearance,

family, sex, violence, religion, and ethnicity. Patients with marked and enduring delusional denial

have been described variously as dogmatic and

inflexible, highly work-oriented with emphasis on

self-sufficiency, reserved with their feelings, and as

regarding incapacity or illness as a personal failure.66,143,144 Patients who had been more emotional

and open with their feelings, and in whom these

were expressed as “physical” symbols such as those

relating to the body, looks, food, and sexual activity, were more likely to have paranoid forms of

denial. Patients with violent backgrounds have

been found to be predisposed to violence after brain

injury.126 As in the case described, patients

who identified strongly with children and whose

lives were structured in terms of a parent-child

relationship may have delusions and preoccupations about children.145 Patients who made inappropriate sexual remarks and gestures, who had

delusions about sex, and who structured their problems in sexual language often had a history

of hypersensitivity to the implications of sex in

personal relationships and of highly stereotyped

views of the roles of men and women.146 It should be

noted that these personality factors contribute to

the behaviors described only after particular types

of brain damage, but it is also noteworthy that

patients with comparable lesions may exhibit

marked differences in the cognitive and affective

aspects of social behavior.

In recent years more attention has been paid to

genetic and early acquired genetic factors, child

abuse and possible brain damage, mental illness

and alcoholism in close relatives, attention deficit

and hyperactivity, and other learning disorders.

Although interest in personality factors has declined, a knowledge of the premorbid personality

characteristics of the brain-injured subject is of great

importance in rehabilitation.93 Discussion with a

patient may help to show him how his own personality may be contributing to his failure in adaptation or conversely be helping him to adapt.

SUMMARY AND CONCLUSION

These are exciting times for the field of TBI. The

understanding of the complex pathogenesis of acute

TBI has grown exponentially over the past few

decades with the delineation of focal injury, diffuse

axonal injury (DAI), hypoxia and ischemia, and

diffuse microvascular injury with loss of autoregulation. With the possible exception of DAI in

penetrating brain wounds, these processes occur in

both closed and penetrating head injuries. This

initial brain damage is followed by secondary tissue injury at the cellular level, involving particularly oxygen free radicals, which affects otherwise

viable tissue, so that much of the loss of function

after TBI is not due to the injury itself but to a

vicious cycle of subsequent biochemical events.

Treatment, along with conventional measures

to control shock and intracranial pressure and to

evacuate hematomas, is aimed at the prevention

and correction of secondary tissue damage. Among

the more promising medical therapies now enter-
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344

ing clinical trials are the inhibiting of lipid

peroxidation with 21-amino steroids, and the control of oxygen free radicals with superoxide

dismutase and catalase.

DAI has been demonstrated even after minor

head injury, and occurs in the absence of morphopathological change in any other vascular, glial, or

neural element. The finding establishes a possible

organic base for “postconcussion syndrome,” once

thought to be of psychological origin.

While penetrating and closed-head injuries (CHI)

share a number of pathological features, there are

clinical differences. Patients with an acceleration/

deceleration CHI are by definition unconscious,

while those with penetrating head wounds frequently do not lose consciousness or have amnesia.

Penetrating head wounds have a much higher incidence of subsequent seizures. The neurological

deficits following penetrating wounds are more

focal and include aphasia, lateralized motor and

somatosensory loss, and visual field defects. Patients with CHI have predominant damage to frontal and temporal limbic structures and are more apt

to develop impairments of memory and attention,

in the perception of reality, and in social and emotional behavior. These differences are not absolute:

penetrating injuries of basilar and other deep brain

structures can result in prolonged unconsciousness

and memory loss.

In recovery from severe head injuries, coma may

be followed by a period of restlessness and agitation, and by a stage of altered interaction in the

environment with features of the amnestic

confabulatory state and the denial syndromes, that

may endure for months. This latter stage involves

not only deficits in cognition, the perception of

reality and affective control, but modes of adaptation to the stresses of reduced capacity.

While long-term cognitive loss depends mainly

on the location of the lesion, notably damage to the

basal forebrain, changes in social and emotional

behavior, such as depression and other mood

changes, and aggressive acts and attitudes derive

not only from lesion location, but from premorbid

experience and environmental events. Return to

work after penetrating wounds sustained in Vietnam was unfavorably affected by post-traumatic

epilepsy, hemiparesis and visual field loss, verbal

and visual memory impairment, psychological problems, and violent behavior. Changes in personality

and affective relationships are less predictable.

It is doubtful if cognitive retraining can enable

the damaged brain to regain lost skills. Rehabilitative measures, however, can provide the patient

with a conceptual or analogical model of what has

happened to him, help him to overcome denial and

recognize both his deficits and remaining strengths,

train him in alternate strategies, and teach him how

to behave in social situations. Drugs have an important role in symptom management, in the control of

disturbances of mood and behavior, in seizures,

and in pain resulting from associated injuries.

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