Initial Management of Head Injury provides comprehensive guidance for non-neurosurgeons on managing patients with head trauma for better patient outcomes. Targeted at emergency physicians, paramedics, general physicians, clinicians and intensivists who are part of trauma care teams, Initial Management of Head Injury gives the non-neurosurgeon all the information they need, enabling them to make accurate decisions for optimal initial care to save lives which may otherwise be lost or irretrievably impaired.

1. PART I
Epidemiology
2 CHAPTER 1 Epidemiology of Acute Head Injury

2. CHAPTER 1
Epidemiology of Acute Head Injury
3 Head Injury: The Magnitude of the Problem
3 Definition of Head Injury
3 Incidence of Head Injury
3 Classification of Head Injury
4 Causative Factors
4 Changing Patterns of Head Injury
5 Organisation of Head Injury Care
7 References

3. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 3
Head Injury: The Magnitude
of the Problem
In developed and in many developing countries, trauma is the
leading cause of death in the population aged under 45 years. In
view of the young age of most victims, more productive years of
life are lost from trauma than from cardiac and cerebrovascular
disease or from cancer.1
Head injuries account for nearly half
the trauma deaths. Although most trauma deaths prior to
hospital admission are due to chest and multiple injuries, head
injury is responsible for the majority of trauma deaths after
hospital admission.2,3
Head injury is also the most common
cause of permanent disability after injury and such disability
may manifest even in patients with less severe degrees of head
injury.4–6
Hence, head injury poses a major public health problem
worldwide. It results in great personal loss and imposes a
tremendous burden on health-care systems through disability
and costs of care, as well as on society through the years of
productive life lost. In the US, an estimated 1.5–2.0 million
people experience a head injury each year; nearly 250000 of
these patients require hospitalisation and approximately 52000
die. Long-term disability affects an estimated 70000–90000
people annually. The economic consequences are considerable.
Lifetime medical care costs of head injuries in the US in 1985
were estimated to total US$4.5 billion, including US$3.5 billion
in hospital costs alone.7–10
In low- and middle-income countries (LMIC), trauma is
an increasingly important cause of death and disability. It has
recently been estimated that the economic burden of trauma for
11 countries in South-East Asia is approximately US$11 billion
per year.11
In these countries, large shifts of rural populations
to urban areas and a rapid increase in the use of motor vehicles
are outpacing efforts at injury prevention and organisation of
trauma care.12,13
The multiple costs of head injury are more
burdensome in these emerging economies.
Definition of Head Injury
Head injury may be broadly defined to include any of
following:15,16
1. a documented history of a blow to the head
2. evidence of injury to the scalp in the form of swelling,
abrasion or contusion
3. evidence of a fracture in a skull X-ray (or computed
tomography (CT) scan) or evidence of brain injury in a
CT scan performed immediately after trauma
4. clinical evidence of a fracture of the skull base
5. clinical evidence of a brain injury (loss or impairment of
consciousness, amnesia, neurological deficit, seizure)
The scalp,skull and brain can be injured independently and only
aproportionof patientswithaheadinjurysustainaconcomitant
brain injury. Conversely, a small number of patients without
initial clinical evidence of an injury to the brain may develop
serious complications, such as intracranial haemorrhage, brain
swelling, meningitis or epilepsy. Consequently, some patients
without clinical evidence of an initial injury to the brain may
need evaluation at emergency departments, and even hospital
admission, making a considerable impact on the health-care
system.14
Incidence of Head Injury
Epidemiological data are of paramount importance in planning
effective preventive measures, planning and providing care for
the acutely injured and rehabilitation for disabled survivors.
Reliable statistics on head injury are difficult to obtain from
routinely collected data from hospital admissions because of
poor identification or categorisation of organ-specific injuries.
In addition, estimates of the frequency of head injuries from
deaths and discharges in hospital statistics do not include
deaths at the site of the injury and omit patients transferred
after initial assessment.13
Epidemiological factors also depend
on geographic, demographic and socioeconomic factors which
vary with time. In many countries, the overall incidence of
head injury is difficult to determine because most statistics are
derived from specific locations and minor head injuries tend
to be under-reported. Hence, data from one country cannot be
used as the basis for planning head injury care in another and
the data from a given location need to be updated constantly.
The epidemiological parameters of head injury (in adults) from
diverse locations are given in Table 1.1. The mean incidence rate
of hospitalised and fatal head injury for Europe is reported to be
235 per 100000 population, similar to the average rate of three
reports from Australia, but much higher than that reported for
the US (103 per 100000) and India (160 per 100000).17–21
The incidence of head injury, based on hospital admissions,
is mostly reported from developed countries and is unlikely
to apply to developing countries. Each year in the UK, 1500
per 100000 population attend an accident and emergency
department with a head injury, 300 are admitted to hospital
and nine die; head injury is implicated in approximately half of
all trauma deaths.22
It has been estimated that for each patient
admitted to hospital with a head injury, approximately three to
four patients with minor head injury are seen and discharged
from emergency departments.23
Classification of Head Injury
Head injury can be classified as outlined below.
By severity of brain injury The most commonly used
modality for classifying brain injury severity is the
post-resuscitation Glasgow Coma Scale (GCS).28
Traditionally, head injury has been classed by severity
as mild (GCS 13–15), moderate (GCS 9–12) or severe
(GCS ≤8). Based on this classification, studies of the
head-injured population in high-income countries
have estimated the incidence among different subsets as
follows: severe head injury 5%; moderate head injury

4. 4 PART I EPIDEMIOLOGY
Causative Factors
In general, the main causes of head injury are road accidents,
falls and assaults. However, there is considerable variation in
the distribution of causes in different countries. Road accidents
are responsible for the majority of head injuries in most
countries.32
World Health Organization (WHO) data show that,
in 2002, nearly 1.2 million people worldwide died as a result
of road traffic injuries (an average of 3242 people dying each
day). The type of road user accounting for most road fatalities
varied in different countries: in Australia, Netherlands and
the US, most were motor car users; in Malaysia and Thailand,
most were motorcyclists; and in India and Sri Lanka, most
were pedestrians. Between 20 million and 50 million people
globally are estimated to be injured or disabled each year from
traffic-related injuries. Head injury accounted for a significant
proportion of such deaths and disability.33,34
Falls are an important cause of head injury,especially among
young children and the elderly. Assault is a more common
cause in economically depressed and densely populated inner-
city areas.35
The importance of civil strife (prevalent for long
periods in some areas of the world) is probably underestimated
as a cause of head injury because of poor documentation.
The US is unique among developed countries in that, in some
locations, firearms have accounted for more head injury deaths
than traffic accidents since 1990.36
Alcoholisanimportantcontributoryfactorinroadaccidents
(affecting pedestrians and drivers), as well as in assaults and
falls. Falls in adults related to alcohol or assault are likely to be
under-reported.
Changing Patterns of Head
Injury
In many developed countries, the trend data for road deaths
from head injury have indicated a decline in recent years,
attributed mainly to the implementation of preventive
measures,such as seat belts,motorcycle and pedal cycle helmets,
laws on alcohol limits for drivers, speed limits and improved car
5%–10%; and mild head injury 85%–90%.23,29
However,
recent studies have demonstrated that patients with
GCS 13 frequently have CT scan abnormalities and develop
intracranial complications requiring surgical intervention,
in a pattern similar to those who are considered to have
moderate head injury.5,30
Hence, in this publication, mild
head injury includes only patients with GCS 14 and 15 at
the time of presentation at the accident and emergency
department. Patients with GCS 13 are considered to have
sustained moderate head injury.
The use of the degree of cerebral concussion and the
duration of post-traumatic amnesia to define injury
severityisdiscussedinChapter4(NeurologiocalEvaluation)
and Chapter 15 (Sports-Related Head Injury).
International Classification of Diseases (ICD)
Code31
This patho-anatomical classification is used for
epidemiological purposes, as well as for hospital record
keeping (see Table 1.2).
Table 1.1 Comparison of selected epidemiological parameters of head injury from different locations
(for adults)
Europe22
US20,24,25
Australia17,19,27 East Asia
(Taiwan)26 India18
Incidence per 100000
population (hospitalised
patients and deaths)
235 103 226 334 160
Mortality rate per 100000
population
15.4 18.1 Not reported 38 20
Severity
(% mild/moderate/severe)
79/12/9 80/10/10 76/12/11 78/9/13 71/15/13
External cause
(% fall/MVA/violence)
37/40/7 21/25/6 49/25/9 23/65/7 59/25/14
MVA, motor vehicle accident.
Table 1.2 International Classification of Diseases
(ICD-10)31
Injuries to the Head (S00–S09)
S 0-0 Superficial injury of the head
S 0-1 Open wound of the head
S 0-2 Fractures of skull and facial bones
S 0-3 Injuries of joints and ligaments of the head
S 0-4 Injury of cranial nerves
S 0-5 Injury of the eye and orbit
S 0-6 Intracranial injury
S 0-7 Crush injury of the head
S 0-8 Traumatic amputation of part of head
S 0-9 Other and unspecified injury of head
Sub categorisation of S 0-6: Intracranial injury
S 06-0 Concussion
S 06-1 Traumatic cerebral oedema
S 06-2 Diffuse brain injury
S 06-3 Focal brain injury
S 06-4 Epidural haemorrhage
S 06-5 Traumatic subdural haemorrhage
S 06-6 Traumatic subarachnoid haemorrhage
S 06-7 Intracranial injury with prolonged coma
S 06-8 Other intracranial injuries
S 06-9 Intracranial injury unspecified

5. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 5
and road design.8,32
In the US, an analysis of national mortality
trends indicated a 22% decline in rates of death associated with
head injury from 1979 to 1992, attributed largely to injury
prevention and improved treatment.8
However, rates for road
deaths may be much higher and rising in LMIC, where such
measures have not yet been implemented and where there has
been a marked increase in vehicular traffic as a result of rapid
economic growth.37
In many developed countries, there has been an increase in
the incidence of head injury caused by falls, especially in the
increasing elderly population. A recent study from Sweden
reported that falls were the most common cause of head injury
(58%), followed by traffic accidents (16%) and persons hit by
objects (15%).38
In some parts of the US, the beneficial effect of a decline
in motor vehicle-related head injury was undermined by a
marked increase in firearm-related head injury.8,34,39
Violence is
unfortunately increasing in prominence as a cause of childhood
injury, especially in economically impoverished areas and in
areas of civil strife.40
Organisation of Head Injury
Care (Table 1.3)
Mortality and morbidity can be significantly reduced by
(i) preventive strategies that reduce the number and severity
of head injuries; and (ii) head injury care systems that aim to
minimise damage to the brain after an injury by optimising:
1. prehospital care and triage
2. initial management at emergency departments
3. urgent evacuation of significant intracranial haematomas
4. high-quality neurointensive care
5. rehabilitation
Instituting these strategies requires reliable data on the
incidence, causation, distribution and degrees of severity
of head injuries in different locations in a country or region
under consideration. Auditing the efficacy of a head injury care
system may identify preventable lapses in management and is
important in the planning and improvement of care.
In an audit of a state trauma service in the state of Victoria,
Australia (published in 2000), the following lapses were
identified.45
Prehospital phase An inability to intubate, prolonged
accident scene time and no intravenous access.
In the emergency room Inappropriate reception, delay in
arrival of a consultant, lack of neurosurgical consultation,
failuretoperformacranialCTscan,inadequatebloodgases
and oxygen monitoring, inadequate fluid resuscitation,
delayed respiratory resuscitation and delayed despatch to
the operating room.
In the operating room Failure to institute intracranial
pressure(ICP)monitoring,inadequatefluidadministration
and inappropriate anaesthetic technique.
Table 1.3 Organisation of a head injury care system33,41–44
Preventive measures
Public awareness programmes that target:
The behaviour of drivers and pedestrians
Workplace accidents (e.g. construction sites, factories)
Accidental injury at home (especially in children)
Legislative measures
Alcohol control (basal alcohol concentration <100µg/dL in most countries)
Speed limits
Use of safety devices (seat belts, airbags, restraints for infants; helmets for motor cyclists, cyclists, construction workers)
Improved infrastructure
Road design, warning devices, speed limits
Improved safety in vehicles
Seatbelts, air bags, infant restraints
Side impact protection
Firearm registration (to reduce the general availability of firearms)
•
•
•
•
•
•
•
•
•

6. Advanced trauma systems developed in developed countries
depend on teamwork involving multiple specialties, proper
sequence and timing of interventions and adequate supporting
equipment, resources and personnel. Such systems may not be
easily adapted to LMIC.51,52
Therefore, a head injury care system
in a given locality must take into account the local conditions,
as well as financial and manpower resources. A study in Latin
America showed that prehospital trauma care can be improved
significantly by instituting simple, low-cost measures such as
Prehospital Basic Trauma Life Support training for emergency
medical personnel, increasing sites of dispatch of emergency
medical personnel, use of oropharyngeal airways, suction,
administration of oxygen, intravenous fluid resuscitation
and cervical collar immobilisation. Implementation of such
measures nearly halved the deaths en route, did not increase
mean time spent at the accident site and increased costs only
minimally.53
In LMIC with limited health care resources, the
institution of preventive measures, organisation of prehospital
care, triage and optimal initial management in emergency
departments will have a substantial impact on the outcome of
trauma.33
6 PART I EPIDEMIOLOGY
In the intensive care unit Failure to institute ICP
monitoring.
Although programmes that provide optimal care for head
injuries of all degrees of severity will reduce mortality and
morbidity, the most profound impact of such programmes has
been the improved management of moderate and mild head
injuries.46,47
Mild injuries are much more common and yet
some patients with mild injury develop life-threatening, but
remediable, complications. Appropriate triage of these patients
is extremely important, particularly when CT scanning and
neurosurgical expertise are scarce.
The publication of practice guidelines for head injury
care (such as those of the Brain Trauma Foundation43
, the
Neurosurgical Society of Australasia48
and the European Brain
Injury Consortium49
) has been very useful in standardising
head injury management. However, a recent study in the US
revealed that only 16% of the trauma centres surveyed were
in full compliance with the guidelines of the Brain Trauma
Foundation.50
Table 1.3 (cont)
Organisation of a trauma-care system
Patient retrieval by a well-designed EMS, with adequately trained EMS personnel, a well-equipped ambulance service acting
in coordination with police and other emergency services; the EMS should provide:
Immediate basic resuscitation at the scene of an accident
Proper triage of the injured
Rapid and safe transfer to an appropriate institution as determined by the nature and severity of the injury
A streamlined referral system based on available resources at trauma care institutions in the region and their proximity
A three-level organisation of trauma care institutions:
Level 3 centres (rural hospitals), with basic care facilities, provide initial resuscitation and safe transfer
Level 2 centres (community trauma centre, district hospital), with a well-designed emergency department with ATLS-
trained staff, emergency operating theatre facilities, the services of a General Surgeon, an Orthopaedic Surgeon, an
Anaesthetist and, optimally, a CT scan facility and, in some level 2 centres, the services of a Neurosurgeon, provide
initial care of head injury if a Neurosurgeon is available on-site or, if a Neurosurgeon is not available, immediate
management of life-threatening extracranial injury, initial resuscitation and evaluation of patients with head injury
(those patients requiring neurosurgical care are transferred to a level 1 centre)
Level 1 centres (regional trauma centres, teaching hospital), with, in addition to facilities available at a level 2 centre, 24
hour availability of CT scanning, a 24 hour neurosurgical service with an operating theatre for emergency neurosurgery, a
well-equipped Neurosurgical Intensive Care Unit, observation wards, facilities for head injury rehabilitation, educational
and research programmes, provide comprehensive management of all aspects of head injury
•
•
•
•
•
•
EMS, emergency medical service; ATLS, advanced trauma life support.

7. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 7
References
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25. Kraus J, McArthur D. Brain and spinal
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26. Chiu W, Yeh K, Li Y, Gan Y, et al. Traumatic
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35. Cooper KD, Tabbador K, Hauser WA, Shulman
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TBI%20in%20the%20US_Jan_2006.pdf
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9. PART II
Basic Principles
10 CHAPTER 2 Pathophysiology of Acute Non-Missile Head Injury
33 CHAPTER 3 Intracranial Pressure

10. CHAPTER 2
Pathophysiology of Acute
Non-Missile Head Injury
11 Introduction
11 Phases of Acute Head Injury
11 Biomechanics of Head Injury
11 Impact Injury
13 Inertial Injury
14 Diffuse Axonal Injury
14 Cranial Injury by Static Loading
14 Primary Brain Injury
14 Focal Injuries
16 Diffuse Brain Damage
18 Evolution of Primary Brain Injury
18 Damage to Parenchymal Cells
19 Damage to the Cerebral Vasculature
21 Secondary Brain Injury
21 Traumatic Intracranial Haematomas
25 Post-traumatic Brain Swelling
26 Focal Brain Damage Secondary to Brain Shifts and Herniations
26 Secondary Brain Insults
26 Secondary Insults due to Extracranial Causes
27 Ischaemic Brain Damage Following Acute Head Injury
28 Mechanisms Contributing to Repair of Damage
from the Initial Injury
28 Role of Genetic Profile in Determining the Outcome of
Head Injury
29 Summary
30 References

11. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 11
INTRODUCTION
The pathophysiological changes following acute head
injury are complex. The injury may be caused by different
mechanisms, often in combination. Changes following
injury occur at the molecular, biochemical, cellular
and macroscopic levels. They are dynamic and may be
adversely influenced by events occuring after the initial
injury.
Phases of Acute Head Injury
Acute head injury is a progressive process.
The initial, or primary, injury is caused by the mechanical
deformation of brain tissue and blood vessels at the moment of
injury. At a macroscopic level, there may be gross disruption of
brain tissue; at a microscopic level, there may be damage to the
brain parenchymal cells (neurones, axons, glial cells) and the
microcirculation (arterioles, capillaries and venules).
The primary injury may evolve over hours or days through
a series of inter-related biochemical and metabolic changes,
inflammatory reactions and progressive structural damage to
neurones, glia and the cerebral vasculature. The consequences
of these dynamic changes include cellular swelling, cell death
by necrosis and apoptosis, intracranial haemorrhage, brain
swelling, raised intracranial pressure and cerebral ischaemia.
Hence, the pathophysiological changes in acute head injury can
be considered at three levels (Fig. 2.1).
Secondary injury refers to the delayed effects of events
initiated by the injury. The term may be applied to the evolving
deleterious effects of the primary injury referred to above but in
clinical terms secondary injury is generally applied to the effects
of post-traumatic intracranial haematomas, brain swelling
and increased intracranial pressure and, in the later stages, to
hydrocephalus and infection.
Secondary brain insults are systemic events occurring
after injury that have the potential to add to the damage to
neurones, axons and the cerebral vasculature, already rendered
susceptible by the primary injury. The principal secondary
insults are hypoxia, hypotension, hypercarbia , hyperpyrexia
and electrolyte imbalances. There is increasing evidence that
the primary injury stimulates reparative processes. Therefore,
the magnitude of any head injury is determined by the total
effects of the primary and secondary brain injury, as well as
secondary brain insults, and may be modified by reparative
processes (Fig. 2.2).1
Biomechanics of Head
Injury
The effects that an injury has on the brain and its coverings
tissues may be analysed in terms of the forces applied. Impact
loading refers to the direct effects that contact has on the head;
for example, when the moving head strikes an object and is
prevented from moving after impact. Impact loading results
primarily in injuries at the site of impact. Inertial loading refers
to the effects of acceleration or deceleration on the brain; for
example, when a pedestrian is struck on the body by a moving
vehicle and the head is set in sudden motion or in a high-speed
motor vehicle collision, when the body of the driver is stopped
by the steering wheel and the head continues to decelerate. The
pattern of brain injury is affected by the subsequent motion
within the cranium. This is invariably a combination of linear
(translational) motion and angular motion.
Most injuries are caused by a combination of impact and
inertial forces. Biomechnical analysis has lead to a greater
understanding of the effects of different types of impact and,
hence, to advances in methods of protecting the brain.
For clinical purposes, it is useful to consider injury in terms
of focal and diffuse components.
Impact Injury
A direct impact to the cranium results in local distortion and
propagation of stress waves from the area of impact through
successively deeper layers of the cranium (i.e. scalp–skull–
meninges–brain parenchyma), the degree of distortion of the
tissue and the depth of propagation of the stress waves being
determined by the velocity of impact. Impact injury usually
involves energy of a high magnitude acting directly on the skull
for a short duration (approximately <50 msec).1
Cascades of cellular,
biochemical, metabolic,
inflammatory changes,
immunological reactions Ischaemic changes, cellular
swelling, cell death (necrosis and
apoptosis)
Macroscopic changes
(focal or diffuse damage)
Contusions, haematoma,
brain swelling, brain shifts
and herniations
Microscopic changes
Neurones, glia
Axonal injury
Changes in the microcirculation
Capillary damage, hypoperfusion,
oedema, hyperaemia,
haemorrhage, ischaemia
▲ Figure 2.1 Spectrum of the pathophysiological changes after acute head injury

12. 12 PART II BASIC PRINCIPLES
▲ Figure 2.2 Overlapping phases of head injury
▲ Figure 2.3 Effects of direct impact injury from a blunt object
with a restricted area of impact. Fragments of bone separate
from the rest of the cranium and are driven below the level of the
surrounding bone, resulting in a depressed fracture (black arrow).
The underlying dura may become lacerated and the underlying
brain may be damaged, resulting in a focal contusion (open
arrows).
Depending on the characteristics of the injury, such as the
energy of impact and the nature of the impacting surface,
several patterns of damage may result, as described below.
Scalp haematoma The dermal and subcutaneous layers
can distribute the force of an impact and reduce its effects
up to a point without structural damage. However, when
the force exceeds the capacity of the scalp to dissipate
the energy, a scalp haematoma or a scalp laceration will
result.
Linear skull fracture When the skull is impacted over a
large area, skull deformation may result, with inward and
outward bending. With a moderate force of impact, or
if the skull is more resilient, as in an infant, inward and
outward bending of the skull may occur without fracture.
However, significant inbending of the more mature, rigid
skull will result in a linear fracture.
Impact forces can propagate stress waves through the
surrounding bone and result in a skull fracture remote from
the impact site. Thus, fractures in the base of the skull may
result from an impact to the skull vault.2
Depressed fracture When the impacting force is distributed
over a relatively small area, such as from a blow by a
hammer, a fragment or fragments of bone may separate
from the cranium and are driven inwards to a depth
equivalent to or more than the thickness of the skull,
resulting in a depressed fracture. The underlying dura may
either remain intact or be lacerated. The underlying brain
may be contused (Fig. 2.3).
Penetrating injury High-energy impact from an object
with a very small surface area (especially a sharp, pointed
object) may lead to deep penetration of the cranium
through very narrow rents in the scalp and cranial bone, as
well as penetration of the dura, and may result in a cerebral
contusion or intracerebral haematoma (Fig. 2.4).
Extradural haematoma The inward and outward bending
of the skull can strip the dura from its attachment to the
inner table of the skull, creating a potential space. If the
dural separation or an overlying skull fracture damages a
meningeal vessel (most commonly the middle meningeal
artery, but also meningeal veins or dural sinuses), an
extradural haematoma (EDH) can result (Fig. 2.5).
▲ Figure 2.4 Impact from a sharp, pointed object resulting in a
penetrating injury. Deep penetration can occur through a very
narrow rent in the cranial bone, resulting in penetration of the
dura and small fragments of bone being driven into the underlying
brain with contusion of the underlying brain (black arrow). An
intracerebral haematoma may also result (white arrowheads).

13. Inertial Injury
Contre coup contusions See Fig. 2.6a–d.
A direct impact can result in movement of the skull and the
brain in a direction away from the impacting force. The brain
lags behind the skull because of its inertia, and because it is
surrounded by cerebrospinal fluid (CSF), and then continues
to move once the skull has stopped. During such differential
movement, the brain can be damaged at points remote from
the impact (e.g. by the irregular surfaces of the floor of the
anterior and middle cranial fossae and the lesser wing of the
sphenoid),resulting in contre coup contusions,typically located
in the frontal and temporal poles and the orbital surfaces of the
frontal lobes (Fig. 2.6a–d). Contre coup contusions may also occur
in the lateral and inferior surfaces of the temporal lobes, as well
as in the cortex above and below the Sylvian fissure.7
Another mechanism for contre coup injury may be the effect
of relative movement between the skull and the brain, leading
to pressure changes in the brain parenchyma, typically at the
poles of the brain (especially in the frontal and temporal poles).
Negative pressure is created at the onset of movement, when
the brain lags behind the skull, and positive pressure is created
when the still-moving brain impacts the stationary skull. When
such pressure change strains exceed the tolerance of the brain
parenchyma and vasculature, contre coup contusions and ICH
can result.
PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 13
▲ Figure 2.5 Direct impact injury leading to an extradural
haematoma (EDH). Direct impact can result in a sub-galeal
haematoma in the scalp (black arrow). The inward and outward
bending of the skull can result in a skull fracture, which is usually
located directly beneath the scalp haematoma. The dura may
become stripped from the inner table of the skull and an EDH
(open arrow) results from a tear in a meningeal vessel.
▲ Figure 2.6 Contre coup contusions after a direct impact
injury. (a) An impact to the occipital region results in differential
movement between the brain and the rough, irregular surfaces of
the floor of the anterior cranial fossa and the temporal fossa (open
arrows). (b) Such motion can lead to cerebral contusions involving
the inferior surfaces of the frontal lobes and the temporal poles
(black arrowheads). (c, d) Computed tomography scans showing
an area of impact over the right parieto-occipital region (white
arrow) leading to contre coup contusions in the frontal lobes
(white arrowheads).
d
c
a
b

14. 14 PART II BASIC PRINCIPLES
▲ Figure 2.8 Effects of compression. Forces of compression
can lead to significant deformation of the skull and extensive
comminuted fractures of the skull vault (black arrowheads) that
may extend to the skull base (curved arrows).
Primary Brain Injury
Focal Injuries
CEREBRAL CONTUSIONS
Contusionsmayresultfromfocalimpactordiffuseacceleration–
deceleration forces. Stress waves propagating from the area of
impactmaydeformbraintissuedirectlyunderneath.Whensuch
strains exceed the tolerance of brain tissue and its vasculature,
there is a disruption of the brain tissue and vasculature that
results in a direct cerebral contusion (coup contusion; i.e. a
contusion directly beneath the site of impact. This is seen most
clearly in contusions that develop beneath a fracture Fig. 2.9
(‘fracture contusions’).
Contusions may also be associated with diffuse injury and
are most commonly located in the frontal pole, orbital surface
of the frontal lobe, the temporal pole and inferior and lateral
surfaces of the temporal lobe. Contusions are often multiple
and may be associated with other lesions, such as acute SDH,
EDH and diffuse axonal injury (DAI).
A contusion may be localised to the cerebral cortex or may
extend deeper to involve the underlying white matter (Fig. 2.10a).
Contusional damage may also extend over the surface of
the cerebral cortex and there may be associated subarachnoid
haemorrhage (SAH). The severity of a contusional injury may
be judged by the surface extent and depth, as well as whether
the damage is solitary or multiple.4
The damage to the vasculature principally involves
capillaries. Disruption of larger blood vessels at a site of impact
can result in an acute SDH (termed ‘complicated SDH’) or an
ICH (Fig. 2.9).
A typical cerebral contusion consists of a central area of
haemorrhageadmixedwithareasof non-haemorrhagicnecrosis
and partly damaged,oedematous brain (Fig 2.10a).With time,this
central area becomes surrounded by a zone of pericontusional
Acute SDH Acute SDH can result from the tearing of veins
that bridge the brain and venous sinuses or the dura
(uncomplicated acute SDH). Less commonly, an acute
SDH can result from the rupture of a cortical artery
(Fig. 2.7a, b).
Diffuse Axonal Injury
(discussed later)
▲ Figure 2.7 Relative movement between the skull and the brain
can result in the tearing of veins that bridge the brain and venous
sinuses or, less often, cortical arteries (inset, curved arrows),
resulting in acute subdural haematoma.
Cranial Injury by Static Loading
This uncommon injury occurs when compressive forces are
exerted on the stationary head (e.g. a wheel of a vehicle or a
heavy weight compressing the head against the floor). Such
forces occur over a longer duration (>200 msec) compared with
impact forces and usually lead to significant deformation of the
skull, extensive comminution of the skull vault and fractures
of the skull base (Fig. 2.8). The degree of brain injury and the
risk of development of an extra-axial haematoma depend on
the force. Because there is no diffuse injury, consciousness may
be preserved, even in the presence of extensive injury to the
cranium.3

15. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 15
▲ Figure 2.10 Cerebral contusion. (a) A computed tomography
(CT) scan demonstrating typical features in a cerebral contusion:
location at the cortical surface and involvement of the grey matter
at the crests of the gyri. There is a central area of haemorrhage
(white arrow) admixed with areas of low density (black arrow)
representing non-haemorrhagic necrosis or partly damaged,
oedematous brain and a zone of pericontusional oedema (white
arrowhead). (b) A CT scan performed within the first 24 hours
after a head injury, showing a small contusion (black arrow) in
the basal portion of the left frontal lobe. (c) A repeat CT scan
performed 72 hours later showing a marked increase in the size of
the contusion due to an increase in the haemorrhagic component
(black arrow), as well as an increase in the surrounding oedema
(white arrowhead).
b
c
a
▲ Figure 2.9 Effects of direct impact injury from a blunt
object, with a broad area of impact. (a, b) The inward and
outward bending of the skull can lead to a linear fracture. The
(a) compressive (small black arrows) and (b) tensile (small open
arrows) strains created can damage the brain parenchyma and
its vasculature, resulting in (c) a direct cerebral contusion (white
arrowheads) and a contusion-related acute subdural haematoma
(large black arrow). (d) Computed tomography (CT) scan showing
a cerebral contusion underneath a comminuted fracture (white
arrows).
a
b
c
d

16. 16 PART II BASIC PRINCIPLES
Herniation contusions occur when the medial parts of the
temporal lobe impinge on the free edge of the tentorium or the
cerebellar tonsils make contact with the foramen magnum at
the time of injury.
Gliding contusions are haemorrhagic lesions in the cerebral
cortex and subjacent white matter that typically result from
shearing injuries and are now considered to be part of the
vascular damage associated with diffuse injuries.2
CEREBRAL LACERATIONS
Cerebral lacerations resemble contusions, except that the pia-
arachnoid on the surface of the involved area in the cerebral
cortex is disrupted. Lacerations of the frontal and temporal
lobes are usually associated with other lesions, such as ICH
and acute SDH. This combination is termed a ‘burst’ frontal or
temporal lobe and the SDH is termed a ‘complicated SDH’.1
Cerebral lacerations may also result from a penetrating
injury of the cranium and depressed skull fractures when the
sharp edges of the in-driven bone may disrupt the underlying
cortex and the pia-arachnoid covering.
Diffuse Brain Damage
The most important cause of diffuse brain damage is shearing
force, which affects all components of the brain, in particular
axons and the cerebral vasculature.2,18
Minor strains cause
transient stretching of the axons and cerebral vasculature.
The typical clinical manifestation of minor diffuse injury is a
momentary loss of consciousness followed by recovery. Axons
subjected to severe strain may undergo immediate disruption,
this process being termed primary axotomy. However, most
axons subjected to shearing strain do not undergo immediate
disruption. Some may undergo progressive swelling followed
by secondary axotomy from 4 hours to several days after
injury. Others, less severally injured, may be able to repair the
cytoskeletal damage.19–21
Axonal injury may be focal or widely distributed in the white
matter of the cerebral hemispheres (diffuse axonal injury)
(Fig. 2.11). Severe shearing strain also leads to diffuse vascular
injury. Diffuse brain injury is often associated with ischaemic/
hypoxic injury and brain swelling.
DIFFUSE AXONAL INJURY
In mild forms of DAI, microscopic foci of axonal damage are
typically distributed in the white matter of the parasagittal
cortex and the corpus callosum. However, with increasing
severity of injury (increased velocity of injury), such foci are
also demonstrated in the internal capsule, the thalami, the
cerebellum and in the ascending and descending tracts of the
brain stem1,3,19,22
(Fig. 2.11a, b). In the more severe forms of DAI,
areas of axonal damage may be sufficiently large to be visible
on magnetic resonance imaging (MRI) as non-haemorrhagic
lesions.23
Adams et al.24
proposed of a grading system for DAI. In
Grade 1 DAI, abnormalities are limited to histological evidence
of axonal damage throughout the white matter without focal
concentration in either the corpus callosum or in the brain stem.
oedema.Insomeinstances,atraumaticICHmaydevelopwithin
a cerebral contusion. Blood flow is characteristically absent in
the central core of the contusion and is reduced in the zone
of pericontusional oedema, where autoregulation is impaired
(vasoparalysis). Therefore, the zone of partially damaged cells
at the periphery of a contusion is vulnerable to any further
reductions in perfusion by a reduction in mean arterial pressure,
increased intracranial pressure or vasoconstriction following
hypocapnia as a result of hyperventilation.5,6
EVOLVING CHANGES IN CONTUSIONS
A contusion may increase progressively in size, beginning
hours after the injury (Fig. 2.10b, c). This may occur as a result of
increased bleeding and/or swelling, as outlined below.
Enlargement of the haemorrhagic component The
haemorrhagic component of the contusion can enlarge by
coalescenceof smallhaemorrhagesordelayedhaemorrhage
secondary to vascular damage. Yamaki et al. demonstrated
that the haemorrhagic component of cerebral contusions
reaches a maximum 12 hours after the injury in 84% of
patients, although some patients may be at risk of delayed
haemorrhage for a longer period.8
Kaufmann assessed
the risk of delayed haemorrhage within a contusion to be
maximal in the first 3–4 days after injury.9
Coagulopathy
associated with injury to the brain parenchyma may
contribute to the risk of delayed haemorrhage.9
A high
incidence of bleeding into the contusions has been
reported to occur in alcoholic patients and patients on
anticoagulant therapy.10
Increased swelling of the central core of the contusion as
well as in the pericontusional zone Partially damaged
brain parenchymal cells in the core, as well as in the
pericontusional zone, may swell (cytotoxic oedema). In
the necrotic areas of the contusion, macromolecules are
degraded into smaller molecules, leading to an increase in
tissue osmolarity, drawing water from the intravascular
compartment into areas of contusion necrosis (osmolar
oedema).11
Swelling in the central area of a contusion
may lead to compression of the pericontusional zone,
resulting in further ischaemia and swelling. Swelling in the
pericontusional area may reach a maximum around 48–72
hours after injury.8,12
The mass effect of cerebral contusions from delayed
haemorrhage and swelling usually peaks around 3–5 days
(although it may range from 24–48 hours to 7–10 days, even,
rarely, up to 3 weeks after an injury).13,14
Usually after the first
week there is a slow reduction in the volume of the contusion
owing to a reduction in swelling, liquefaction and resorption of
the haemorrhagic component.
Even small contusions that initially appear relatively
innocuous have the potential to enlarge and cause increased
intracranial pressure. Sudden and catastrophic deterioration
may occur in patients who initially appeared relatively
neurologically intact (the ‘talk and die’ or ‘talk and deteriorate’
category).15
Contusions in the temporal fossa and those
involving both frontal lobes are most likely to lead to such
deterioration.16,17

17. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 17
is related to the level of consciousness immediately after the
injury, the duration of the post-traumatic unconscious state
and the outcome from head injury. Patients who sustain severe
DAI may succumb in the early stages after injury or survive
with severe impairment.
Concussion is a clinical term that implies immediate but
transient impairment of the conscious state after a head injury,
followed by complete recovery of consciousness. Magnetic
resonance imaging and post-mortem pathological studies have
found evidence of axonal injury in deep white matter tracts
and in the brain stem in patients who had made an apparently
complete recovery from concussion.18,23
These lesions may
be the basis for persistent symptoms and neuropsychological
sequelae in some patients after a typical concussional injury. In
a patient who recovers from concussion without any sequelae,
the disturbance of axonal function may have been transient or
the degree of permanent injury too small to detect.14
Clinical
grading of concussion is discussed in Chapter 18.
DIFFUSE VASCULAR INJURY
The cerebral blood vessels are more resistant to shearing
strain than axons. The effects of damage to the cerebral
microvasculature has already been described. Severe forms of
diffuse vascular injury may be evident as multiple petechial
haemorrhages and are often found in patients who die within
minutes of a closed head injury.25
Tissue tear haemorrhages
associated with DAI that are small (<2 cm in diameter),
discrete and located in typical sites (corticomedullary junction,
deep white matter, basal ganglia and posterolateral midbrain)
are also a form of diffuse vascular injury.
Grade 2 DAI is defined by a wider distribution of axonal injury
accompanying a larger focus of axonal damage in the corpus
callosum, whereas Grade 3 DAI is characterised by diffuse
damage to axons associated with larger foci of axonal damage
in both the corpus callosum and brain stem. Haemorrhage
may occur in the larger foci of axonal damage in the corpus
callosum and brainstem as a result of diffuse vascular damage
(Fig. 2.11c).24
Diffuse axonal injury disrupts the neuronal interconnections
between the cerebral cortex and the brain stem reticular
formation. Disruption of these interconnections contributes to
impairment or loss of consciousness in patients who sustain
head injury. With progressively severe injury, the extent and
depth of axonal injury increases.18
Hence, the severity of DAI
a
b
▲ Figure 2.11 Diffuse axonal injury. (a) Shearing forces in the brain (curved arrows) created by angular motion. (b) Foci of microscopic
diffuse axonal injury distributed throughout the parasagittal white matter in the cerebral hemispheres (open arrows), in the corpus
callosum, typically in the splenium (black arrow), and in the dorsolateral aspect of the midbrain (black arrowhead). (c) Computed
tomography scan showing a haemorrhagic focus of axonal damage (a ‘marker’ lesion) in the deep white matter (white arrow).
c

18. Evolution of Primary
Brain Injury
Damage to Parenchymal Cells
The forces associated with the primary injury may immediately
and irreversibly destroy some neurones, axons and glial cells.
In partially damaged cells and axons, complex biochemical
and metabolic events are initiated, which may lead to cellular
swelling and delayed cell death over a period of minutes to
days.21
These events initiated by mechanical deformation are
extremely complex and incompletely understood. They include
the following.
Excitotoxiccascade Inthisscenario,mechanicaldeformation
of the neuronal cell membrane results in depolarisation,
major ionic fluxes and the release of excitatory amino
acids, such as glutamate. There is an efflux of intracellular
potassium and an influx of extracellular sodium and
calcium. The entry of sodium and calcium is accompanied
by water. The excess potassium in the extracellular space is
takenupbyastrocytes,whichswell.21,26
Theinfluxofcalcium
into the neurone activates enzymes, including calpains,
which destroy the internal architecture (cytoskeleton) of
the cell, interfere with mitochondrial energy production
and trigger the release of free radicals. Free radicals initiate
cell membrane lipid peroxidation, further disruption of
ionic permeability, further cellular swelling and, finally,
cell death through both necrotic and apoptotic processes
(Fig. 2.12).21,26
Inflammatory cell responses Trauma-induced cytokine
release and leucocyte accumulation in the injured brain
18 PART II BASIC PRINCIPLES
Initial injury
Release of excitatory amino acid
neurotransmitters
(glutamate, aspartate)
Injury induced cell membrane depolarisation
Opening of gated ion channels
Increased influx of calcium
into the cell
Increased influx of sodium
chloride and water into the cell
Efflux of intracellular potassium
into the extracellular space
Activation of proteases
(calpains), lipases
Destruction of cellular
cytoskeleton
Delayed cell deathCellular swelling
(cytotoxic oedema)
Swelling of glial cells,
extrinsic compression of
capillaries, ischaemia
▲ Figure 2.12 Excitotoxic cascade. The sequence of deleterious events in brain parenchymal cells, triggered by the excitotoxic cascade
and their consequences.21,26,27

19. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 19
tissuesuggestthatinflammationmaycontributetotraumatic
cellular and vascular injury.28
Intra- and perivascular
accumulation of polymorphonuclear leucocytes occurs
approximately 24 hours after injury. This is followed by a
delayed phase of inflammation dominated by macrophage
infiltration, peaking at approximately 3–5 days.29
The
macrophages can secrete a range of factors, including
cytokines,tumour necrosis factor and interleukin (IL)-1 and
IL-6,which may contribute to the release of free radicals and
increase capillary permeability by changing the blood–brain
barrier. Conversely, some aspects of the neuroinflammatory
response may be involved in promoting repair.30,31
Metabolic changes Cerebral oxidative metabolism (cerebral
metabolic rate for oxygen (CMRO2)) remains depressed
by approximately 50% in comatose head injury patients
for the first 2 weeks after a severe head injury. The degree
of depression has been shown to be correlated with long-
term outcome.32
Changes in glucose metabolism after
acute head injury follow a triphasic pattern. An early,
brief hyperglycolytic phase may reflect increased energy
demands in attempting to reverse ionic imbalances. This is
followed by a‘metabolic depression’ phase that may last up
to 30 days after injury. The third stage is gradual recovery.33
In damaged regions of the brain, lactate levels increase as a
result of anaerobic metabolism.
CONSEQUENCES OF THE EVOLUTION
OF CELLULAR DAMAGE
Vulnerability of Partly Damaged Cells
Partially damaged cells are more vulnerable to secondary brain
insults. Brain parenchymal cells need a high rate of energy
production to maintain cell integrity and the ionic gradients
needed for impulse generation. The oxygen and glucose
requirements of brain tissue are higher than those of most
other organs and energy stores are limited. These features
account for the extreme vulnerability of brain parenchymal
cells to ischaemia. Any further insults to partially damaged
cells in the immediate postinjury period, particularly hypoxia,
focal ischaemia or reduced cerebral perfusion pressure, may
acceleratetheadversecascadesof changesandresultincelldeath.
Ischaemia may also occur as a result of vasoconstriction that
follows severe hypocapnia (reduced PaCO2
) or vasospasm.
Ischaemia is also aggravated by the increased metabolic
demands of injured cells as a result of seizures or pyrexia. It is
important to realise that most secondary ischaemic insults
in the early postinjury period are preventable.
Cerebral Oedema
Accumulation of water in neurones and glial cells results
in cellular swelling (cytotoxic oedema). This is considered
to be one of the principal factors contributing to increased
intracranial pressure in the early postinjury period.34,35
Cytoprotective Therapy
As knowledge developed of the sequential changes following
head injury, several pharmacological ‘neuroprotective’ agents
were developed and underwent clinical trials. These included
free radical scavengers, glutamate antagonists and calcium
channel blockers. None has proven beneficial at the time of
printing. Clearly, a proven ‘neuroprotective’ therapy would be a
major breakthrough in head injury management.36
Damage to the Cerebral
Vasculature
Damage to the cerebral microvasculature may lead to:
(i) narrowing and distortion of the capillary lumen by swelling
of capillaryendothelialcells,extrinsiccompressionof capillaries
from swollen glial cells, increased leucocyte adherence to
capillary endothelium and sludging of red cells; (ii) disruption
of the blood–brain barrier, resulting in transendothelial passage
of water, ions and protein-rich fluid into the extracellular space
(vasogenic oedema); (iii) pericapillary haemorrhage, which
may coalesce and enlarge, contributing to the progression of
the haemorrhagic component in cerebral contusions; and
(iv) loss of autoregulation or vasoparalysis, with vasodilatation
and hyperaemia (congestive brain swelling) (Fig. 2.13a, b).26,35
a
(b)b
▲ Figure 2.13 Effects of progression of the initial injury in the
microcirculation. (a) Uninjured capillary. (b) Changes in the injured
capillary leading to reduced flow in the microcirculation, including
narrowing and distortion of the capillary lumen by swelling of
capillary endothelial cells (open arrows), extrinsic compression by
swollen glial cells (large black arrows), leucocyte adherence to the
capillary endothelium (small black arrow) and sludging of red cells
(black arrowheads).

20. CONSEQUENCES OF DAMAGE
TO THE MICROVASCULATURE
Reduction of Regional Cerebral Blood Flow
(Hypoperfusion)
Pathological changes in the microvasculature and surrounding
glial cells can contribute to regional post-traumatic
hypoperfusion.2
The loss of endogenous vasodilators (such
as nitric oxide) and liberation of vasoconstrictors (such as
endothelin-1) are also thought to contribute to early post-
traumatic hypoperfusion.38,39
There may be a significant global reduction in cerebral
blood flow during the early postinjury period (especially in the
first 6–8 hours) after severe head injury. There may also be focal
reductions in blood flow around cerebral contusions and in the
cerebral hemisphere underlying acute SDH.5,21,26,37,40–42
Current
investigations suggest heterogeneity in the degree of perfusion
in different regions of the brain after acute head injury.43
Injured brain cells are particularly vulnerable to any
reductionsinperfusion,contributingtothecommonoccurrence
of ischaemic cell change in patients after severe head injury.17
Brain Swelling and Increased Intracranial
Pressure
Extracellular oedema (vasogenic oedema) may result from
increased capillary permeability due to disruption of the blood–
brain barrier.28
Hyperaemic brain swelling may also result
from vasoparalysis and vascular engorgement (hyperaemia).
Vasogenic oedema and hyperaemia can contribute to post-
traumatic brain swelling (and, hence, increased intracranial
pressure) in the later stages of acute head injury.
Impairment of Autoregulation
Autoregulation is the capacity of the cerebral microvasculature
to adjust cerebral blood flow in response to changes in cerebral
perfusion pressure or changes in cerebral metabolism. The
ability of the cerebral arterioles to change their calibre is termed
vasoreactivity.
PRESSURE AUTOREGULATION
The cerebral perfusion pressure (CPP) is the net force driving
arterial blood into the cranial cavity:
CPP=MAP–ICP
where MAP is mean arterial blood pressure and ICP is
intracranial pressure.
In the uninjured brain, pressure autoregulation maintains
a constant cerebral blood flow (CBF) within a range of CPP
between 50 and 150 mm Hg. An increase in CPP leads to
vasoconstriction of the arterioles. Conversely, a reduction in
CPP leads to vasodilatation.
METABOLIC AUTOREGULATION
Normally, CBF is coupled to the cerebral metabolic rate; CBF
is diminished in patients who are in deep coma, in whom the
cerebral metabolic rate is reduced. Conversely, CBF increases
with seizures or pyrexia when there is an increase in cerebral
metabolism. If CBF falls, there is a fall in tissue oxygen, a fall
in pH and an increase in tissue carbon dioxide levels. These
metabolic changes stimulate vasodilatation and increase CBF.
In a significant proportion of patients with severe head
injury, cerebral autoregulation is impaired. The impairment
of autoregulation is most evident in the immediate postinjury
phase and may improve over time.44–48
The loss of the capacity to
increase cerebral perfusion in the face of threats such as hypoxia
and hypotension contributes to the increased vulnerability of
the injured brain to secondary insults.28,49
The distribution of
impairment of autoregulation in the cerebral vasculature may
be asymmetric, with the more damaged portion of the brain
demonstrating greater impairment.45,46,48
Impaired autoregulation has also been demonstrated in
patients after mild and moderate head injury, emphasising
the importance of maintaining an adequate cerebral perfusion
pressure (CPP) even in patients with less severe injury.21,50
The deleterious consequences of impaired autoregulation
are further discussed in Chapter 3.
CARBON DIOXIDE REACTIVITY
Arteriolar calibre, and hence CBF, is sensitive to changes in
the pH in the perivascular spaces of the arterioles and, thus,
to changes in arterial CO2
levels. Hypercarbia leads to a fall
in pH, arteriolar dilatation and an increase in cerebral blood
volume and CBF (potential for increased intracranial pressure).
Hypocapnia leads to an increase in pH, arteriolar constriction
andadecreaseinCBF(potentialforischaemia).Inmostpatients
with severe head injury, CO2
reactivity is temporarily disturbed,
but returns to normal within 24 hours. The vulnerability to
hypocapnia is especially significant because the damaged vessels
in the ischaemic areas of the contusions may retain reactivity to
changes in PaCO2
even though pressure autoregulation is lost.5,6
Marion et al.51
demonstrated that CO2
reactivity was increased
in the hemisphere underlying acute SDH. Patients with severe,
persistent impairment of CO2
reactivity die or remain severely
disabled.52
CONSEQUENCES OF DAMAGE TO LARGER
INTRACRANIAL VESSELS
Haemorrhage
Extradural haematoma From injury to dural vessels
(middle meningeal artery and vein, other meningeal
vessels or the dural venous sinuses).
Acute subdural haematoma From rupture of bridging
veins, that extend between the dural venous sinuses or less
commonly arteries between the dura and brain surface, the
sylvian veins.
Contusion/laceration-related acute SDH From rupture
of cortical arteries or venules, most often with injuries to
frontal, temporal poles (‘burst lobes’).
Intracerebral haematoma From rupture of deeply situated
perforating vessels in the brain parenchyma.
Ischaemia
Vascular injury and ischaemia may also follow stretching
and distortion of brain vessels as a result of mechanical
20 PART II BASIC PRINCIPLES

21. b
a
▲ Figure 2.14 Extradural Haematoma (EDH). (a) A computed
tomography (CT) scan demonstrating an EDH, typically located
directly beneath the area of impact, as indicated by the overlying
scalp haematoma. (b) A CT scan with bone window settings
demonstrating a skull fracture (white arrowhead).
displacement (brain shift or herniations caused by intracranial
hypertension) or as a result of vasospasm secondary to
traumatic subarachnoid haemorrhage.2
Ischaemia may also
occur from damage to major extracranial vessels (e.g. traumatic
dissection, stenosis or thrombosis of the internal carotid artery
with distal embolisation) or primary traumatic occlusion of the
middle cerebral artery.53
Secondary Brain Injury
Traumatic Intracranial
Haematomas
EXTRADURAL HAEMATOMA
Extradural haematoma has been reported in up to 4% of all
patients who have a computed tomography (CT) scan after
acute head injury and in approximately 9% of all patients
who are unconscious at admission. Most EDH occur in the
second or third decade, when the dura is less densely adherent
to the overlying cranium than in the newborn and elderly
and, therefore, more easily stripped from the cranium after
an impact. Hence, EDH is rare in the newborn and elderly, in
whom the dura is tightly adherent to the cranium.54–56
An EDH is usually located directly beneath the point of
impact and is associated with a skull fracture in 66%–95% of
instances (Fig. 2.14).55
However, in children <15 years of age, an
EDH may occur without skull fracture because the skull is more
pliable and can deform without fracturing. Although a blow to
the head or a fall has the most potential to cause EDH, motor
vehicle accidents, being more common mechanisms of head
injury, account for nearly 50% of all EDH. In infants and young
children, most EDH result from falls.56
Most EDH occur in the temporal or temperoparietal region
(62%–80%), with the frontal area (7%–18%), posterior fossa
(4%–11%) and vertex being less common sites.55
The anterior or posterior branches of the middle meningeal
vessels are the source of bleeding in approximately 80% of EDH.
In vertex and posterior fossa haematomas, a dural venous sinus,
diploic veins or other meningeal vessels may be the source.
Usually the EDH is confined to the area where the dura was
stripped at the initial impact. However, brisk and continued
arterial bleeding may produce rapidly increasing pressure
within the EDH, resulting in progressive stripping of the dura
and a rapidly expanding EDH.54
Associated Lesions
Intradural lesions, in particular acute SDH and cerebral
contusions, are associated with 27%–38% of EDH.54
The
incidence of associated lesions is much higher (50%–70%) in
patientswhoarecomatose.57
Associatedlesionsmaysignificantly
influence the clinical picture and outcome.
Posterior Fossa EDH
Extradural haematoma is the most common traumatic
intracranial lesion in the posterior fossa and is most often seen
during the second and third decades of life.58
There is usually
an impact injury in the occipital region and a fracture crossing
the transverse, sigmoid or confluence of sinuses.
PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 21
SUBDURAL HAEMATOMA
Subdural haematomas are classified as acute, sub-acute or
chronic depending on time of presentation after injury. Acute
SDH presents within 48 hours, subacute SDH presents between
48 hours and 2 weeks, whereas chronic SDH presents after
2 weeks.59
Acute Subdural Haematoma
Acute SDH has been reported in 11% of all patients with acute
head injury and in 21% of those with severe head injury.57
The mechanism of injury responsible for the development
of an SDH differs between age groups, with motor vehicle-

22. related accidents (MVA) being the mechanism in a majority
of younger patients and falls accounting for most SDH in the
older age group (>65 years). In comatose patients, MVA are the
mechanism of injury in 53%–75% of SDH.57
Cerebral atrophy
with an increase in the potential subdural space increases the
risk of acute SDH in chronic alcoholics and the elderly.
The usual source of bleeding is a ruptured bridging vein,
although at times a cortical artery may be the source (Fig. 2.7).2
When SDH is associated with a cerebral laceration, damaged
pial vessels contribute. When a surface artery is the source of
bleeding, rapid deterioration of consciousness may occur,
similar to the common presentation of an EDH.60
LESIONS ASSOCIATED WITH ACUTE SDH
Unilateral hemisphere ischaemia and swelling Brain
compression caused by the SDH may lead to ischaemia
in the microcirculation and brain swelling (Fig. 2.15).42
Venous compression may also be a factor. The force that
generates the SDH may also be responsible for hemisphere
damage and swelling. In some instances, the acute SDH
may be very thin, but may be accompanied by significant
unilateral hemisphere swelling that accounts for most of
the mass effect.
Diffuse axonal injury, cerebral contusions and
intracerebral haematomas (ICH) Acute SDH may be
accompanied by DAI, cerebral contusions and ICH.
‘Burst lobe’ Complicated acute SDH is associated with a
laceration of the frontal or temporal lobe and intracerebral
bleeding (‘burst lobe’). Solonuik et al. described that 28%
of cases of traumatic ICH are associated with an acute
SDH.16
Patients with acute SDH and coexistent unilateral
hemisphere swelling and/or associated lesions often
present with a severe degree of neurological impairment
and have the potential for further deterioration. This
underscores the need for early intensive management
once an acute SDH is detected.
Subacute SDH
Subacute SDH becomes symptomatic between 48 hours and
2 weeks after injury. These lesions are usually not accompanied
by significant associated injury. The haematoma undergoes
degradation and is usually a mixture of semisolid and fluid
blood at the time of presentation.
Chronic SDH
Chronic SDH becomes symptomatic 2 weeks or more after
trauma and is more commonly seen in the elderly or chronic
alcoholics. Chronic SDH is also liable to occur in patients with
coagulopathy, chronic epilepsy and those with CSF shunts. The
head injury may be of a minor nature or, indeed, there may
be no history of a head injury. A chronic SDH is thought to
originate from a small asymptomatic SDH that becomes
enclosed in a membrane containing numerous fragile, enlarged
capillary vessels (macrocapillaries). Continued bleeding and
escape of plasma from these fragile capillaries is thought to
contribute to gradual enlargement of the haematoma.13
Several
layers of membranes may develop and haematomas of different
stages of evolution may be evident in one location. Absorption
of fluid into the haematoma by osmotic mechanisms may also
play a role in enlargement of the lesion.
Subdural hygroma
This is a collection of CSF that accumulates in the subdural
space as a result of tear in the arachnoid allowing CSF to enter
the subdural space in a valvular fashion. Effusion of fluid from
injured vessels in the meninges or in the underlying parenchyma
may also play a role.61,62
The fluid in a subdural hygroma is
usually clear and xanthrochromic, although at times it may be
blood stained.
INTRACEREBRAL HAEMATOMAS
A typical traumatic ICH is a well-defined, homogeneous
collection of blood within the brain parenchyma in contrast
with a cerebral contusion,which is an ill-defined,heterogeneous
lesion comprising areas of haemorrhage, partially damaged
brain parenchyma and necrotic brain. However, this distinction
is not always clear because a contusion with a predominantly
haemorrhagic component may appear as a traumatic ICH.
Traumatic ICH have been reported in approximately 15% of
patients with fatal head injury.63
Solonuik et al.16
reported that
28% of traumatic ICH was associated with SDH and 10% with
EDH. Most cases of traumatic ICH result from direct rupture
of small vessels within the parenchyma secondary to a contre
coup injury. Hence, traumatic ICH are often multiple and most
frequently (in 80%–90% of cases) occur in the white matter of
the frontal and temporal regions. As a result of the common
biomechanical mechanisms involved in their production, ICH
may be associated with lobar contusions and SDH, the ‘burst
lobe’.33,64,65
22 PART II BASIC PRINCIPLES
▲ Figure 2.15 Acute subdural haematoma (AcSDH). A computed
tomography scan demonstrating an AcSDH with ischaemia and
swelling of the underlying cerebral hemisphere, contributing to a
significant mass effect.

23. a
b
▲ Figure 2.16 Intracerebral haematoma (ICH) secondary to
penetrating injury. (a) A computed tomography scan with ‘bone’
window settings demonstrating a narrow area of disruption of
the cranium (white arrow) by a penetrating injury; there is also
evidence of air in the subdural space (white arrowhead). (b) ‘Brain’
window settings showing an ICH (white arrow).
PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 23
Traumatic Basal Ganglia Haematomas
Intracerebral haematomas occur in the thalamus and basal
ganglia in approximately 3% of patients with severe closed
head injury.66
These haematomas are often associated with
diffuse axonal injury and are thought to result from shearing
of deep penetrating branches of the anterior choroidal and
lenticulostriate arteries.67
They are often associated with a poor
prognosis.
POST-TRAUMATIC INTRAVENTRICULAR
HAEMORRHAGE
Post-traumatic intraventricular haemorrhage has been
reported in as many as 25% of patients with severe head injury.
Parenchymal haemorrhages and basal ganglia haemorrhages
may extend into the ventricular system. Intraventricular
haemorrhage in the absence of parenchymal or basal ganglia
haemorrhages is due to tearing of veins in the fornix, septum
pellucidum or the choroids plexus and is an indicator of a
shearing injury.68,69
TRAUMATIC SUBARACHNOID
HAEMORRHAGE
Traumatic SAH (tSAH) usually results from shear injury to
vessels in the subarachnoid space. In the Traumatic Coma Data
Bank Study of patients after severe head injury, 39% showed
CT scan evidence of tSAH as hyperdense collections of blood in
the cerebral sulci, Sylvian fissures and basal cisterns. The risk of
mortality rose nearly twofold when tSAH was evident in the CT
scan.70
In addition, tSAH may occur at sites of contact injury as
a result of disruption of superficial vessels.
HAEMATOMAS IN THE CEREBELLUM AND
BRAIN STEM
Traumatic haematomas in the cerebellum and brain stem are
uncommon, being detected in approximately 3% of patients
who have CT scans after acute head injury.71
CEREBELLAR HAEMATOMAS
Intraparenchymal haematomas of the cerebellum may develop
within areas of cerebellar contusions (which are often a result
of direct impact) or may develop after a delay in areas of
the cerebellum that appear normal on the initial CT scans.72
Traumatic cerebellar haematomas in children which are often
associated with an occipital fracture.73
BRAIN STEM HAEMATOMA
Two types of traumatic brain stem haematomas have been
described:72,73
(i) those associated with diffuse axonal injury,
usually located in the dorsolateral part of the upper brain
stem; and (ii) secondary brainstem haemorrhages or Duret’s
haemorrhages caused by brain stem compression and distortion
associated with increased ICP and brain herniation, usually
located centrally in the pons or midbrain. Blumbergs also
described brain stem contusions, lacerations in relation to skull
base fractures and disruptions at the mesencephalic–pontine,
pontomedullary and medullocervical junctions.74
An ICH may also develop beneath the site of impact (e.g.
adjacent to a linear or depressed fracture) or as the result of a
penetrating injury (Fig. 2.16a, b).
The mass effect secondary to a traumatic ICH may increase
with time due to perilesional swelling or from continued
bleeding. Delayed ICH may develop in regions that appear
normal in an early CT scan, underlying the need for repeat
scanning in patients with severe head injury, even when
the initial scan was normal, whenever there is unexpected
deterioration (see Chapter 5, Radiological Evaluation).

24. PROGRESSION OF INTRACRANIAL
HAEMORRHAGIC LESIONS AND
DEVELOPMENT OF NEW HAEMORRHAGE
Acute head injury is a dynamic process and progressive changes
that can lead to an increase of the mass effect and intracranial
pressure. These changes are: (i) enlargement of existing
mass lesions; (ii) development of new mass lesions; and (iii)
progression of brain swelling.
French and Dublin75
demonstrated that 52% of patients
with acute head injury developed new lesions or progression
of known lesions in follow-up CT scans. Gentleman et al.76
demonstrated delayed traumatic intracranial haematomas in
15%–20% of patients with severe head injury. A mass effect
secondary to evolution of existing lesions or the development of
new lesions is the most common cause of sudden neurological
deterioration in patients who may be relatively intact at initial
assessment.77–79
Delayed Lesions with Diffuse Brain Injury
In a recent study of patients with moderate and severe head
injury whose initial CT scan showed evidence of a diffuse injury,
one of six showed evidence of deterioration in a subsequent CT
scan. A new mass lesion was evident in 74% of patients who
showed CT evidence of deterioration, worsening prognosis.80
Delayed Lesions After Normal Initial CT
Scans
The incidence of delayed lesions after a normal initial CT scan,
is low (4%–9%) in current studies of comatose patients when
high-resolution CT scanners are used.80,81
Mechanisms responsible for delayed haemorrhage in
patients with acute head injury include the following.82–87
Delayedruptureofbloodvesselspartiallydamagedduring
initial injury This may be precipitated by an increase
in intravascular pressure secondary to vasodilatation
following loss of autoregulation or as a result of hypoxia or
hypercarbia. Surges in blood pressure in restless patients
or restoration of blood pressure in a hypotensive patient
may also contribute.
Release of tamponade effect This may follow a rapid
decrease of ICP after surgical removal of a large
intracranial haematoma or administration of a bolus dose
of intravenous mannitol or excessive CSF drainage.
Coagulopathy secondary to brain injury This is discussed
in the next section of this chapter.
Disseminated coagulopathy Disseminated coagulopathy
may occur after severe trauma or as a result of premorbid
coagulopathy (e.g. due to anticoagulant medication,
alcohol intoxication or liver dysfunction).
The lesions most likely to show delayed enlargement are cerebral
contusions, ICH and EDH.73,88
Delayed enlargement of EDH Approximately 25% of EDH
enlarge in the postinjury period, within a mean interval of
8.2 hours from injury to reaching their final size (range
6–36 hours after injury).89–91
Approximately 8% of EDH
appear after an initially negative CT study.92
Delayed enlargement of acute SDH Delayed development
of acute SDH is considered rare, with some small acute
SDH reported to disappear or decrease in volume.88
However, delayed enlargement of acute SDH has been
reported after restoration of blood pressure in hypotensive
patientsandafterevacuationof largetraumaticintracranial
haematoma.83
Acute SDH in the posterior fossa may
enlarge during the first 4 days after injury, especially when
it is associated with parenchymal cerebellar injury.93
Delayedenlargementofcerebralcontusions Mostcerebral
contusions increase in size or appear as new lesions during
the first 12 hours (Fig. 2.13b, c).88
The maximal mass effect
due to new haemorrhage and swelling usually occurs at
3–5 days, although this may range from the first
24–48 hours to 10 days or, rarely, even up to 3 weeks
after an injury.8,12–14
Statham et al.17
demonstrated that
most patients with bifrontal contusions show evidence of
progression by 3 days postinjury, but some deteriorate as
late as 9 days after injury.
Delayed traumatic ICH Delayed traumatic ICH (DTICH)
is defined as an ICH that develops in an area of the brain
that was non-haemorrhagic on a previous CT scan.13,56,57
Since the advent of CT scanning, it has been recognised
that ICH may develop hours to days or even weeks after an
acute head injury, even though an immediate postinjury
CT scan may not show their presence.9,94
Although a 3.5%
incidence of DTICH has been reported among all head-
injured patients, the reported incidence in patients with
moderate and severe head injury is 3.3%–7.4%.9,56,76
COAGULOPATHY SECONDARY TO BRAIN
INJURY
Coagulation consists of conversion of fibrinogen to fibrin by a
cascade of enzymatic changes initiated by tissue and/or vascular
injury.The strands of fibrin trap blood cells (platelets) to form a
clot.Coagulationitself,aswellasplateletactivity,releasesaseries
of inflammatory mediators that promote further coagulation.
Brain tissue is very rich in thromboplastin. The release of
tissue thromboplastin by brain parenchymal damage and the
damaged endothelium of the cerebral vasculature, as well as
platelet activation, can lead to hypercoagulation, fibrinolysis
and a depletion of clotting factors locally in the brain.
The consumption of coagulation factors is reflected by
changes in coagulation parameters: elevation of prothrombin
time (PT), activated partial thromboplastin time (APTT),
decreased serum levels of fibrinogen and increased serum levels
of fibrin degradation products (FDP) and D-dimer. These
changes are found to peak at about 6 hours after the injury and
return to normal values at 24–36 hours.95
Deleterious Consequences of Coagulopathy
Secondary to Brain Injury
Increased risk of post-traumatic haemorrhage Delayed,
as well as progressive, post-traumatic haemorrhage has
24 PART II BASIC PRINCIPLES

25. been linked to abnormalities of brain injury induced
coagulopathy.86,96
Intravascular microthrombosis and cerebral ischaemia
Microthrombi leading to ischaemic brain damage have
been demonstrated in rats with fluid percussion injury,
pigs with diffuse axonal injury and in contused brain tissue
removed from patients with acute head injury during
surgical decompression.95
Aggravation of postinjury inflammatory changes
Blood coagulation can result in an excessive release of
inflammatory mediators, such as cytokines, which can
damage parenchymal cells and the vascular endothelium
directly, leading to aggravation of ischaemic brain
injury.97
Post-traumatic Brain Swelling
Brain swelling implies an increase in ‘brain bulk’. This can
result from an increase in brain tissue water (brain oedema),
an increase in intravascular blood volume (hyperaemia or
vascular engorgement) or a combination of both mechanisms.4
Traumatic brain oedema is considered to contribute most to
post-traumatic brain swelling.35
TRAUMATIC BRAIN OEDEMA
The two principal types of traumatic brain oedema are cytotoxic
oedema (intracellular oedema) and vasogenic oedema.
Cytotoxic (Intracellular) Oedema
Cytotoxic oedema results from the intracellular accumulation
of water in neurones and glia. Primary damage to parenchymal
cells leads to energy depletion, failure of the active ion pumps
and increased permeability of the cell membrane to sodium
and water, leading to accumulation of sodium and water in the
cells.Cytotoxic oedema can also be aggravated by ischaemia and
hypoxia.98
Astrocytes outnumber neurones and can swell up to
five times their normal size. Hence, glial swelling is considered
the main contributor to cytotoxic oedema.98,99
Vasogenic Oedema
Vasogenic oedema is the accumulation of fluid in the
extracellular space. Primary injury to the microvasculature can
lead to disruption of the blood–brain barrier, with increased
capillary permeability and escape of protein-rich fluid from
the intravascular compartment into the extracellular space.
Vasogenic oedema is seen around cerebral contusions.26
Other important, although less common, mechanisms of
traumatic brain oedema include the following.
Osmotic oedema (osmolar swelling)
Osmotic oedema develops as a result of osmotic imbalances
between extracellular and intracellular compartments, leading
to entry of water into cells. Such an imbalance occurs in areas
of contusion necrosis when macromolecules are broken down
into smaller molecules.11,50
Osmotic oedema may also occur as a
result of a reduction in the osmolarity of the extracellular space,
in hyponatraemia.
PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 25
Interstitial oedema due to obstructive
hydrocephalus
An obstruction to CSF outflow results in the accumulation of
water in the extrcellular space in the periventricular region.
Hydrostatic oedema
Hydrostatic oedema may follow an increase in intravascular
pressure in an intact vascular bed when loss of autoregulation
is combined with high systemic blood pressure or after surgical
decompression.
Earlier studies suggested that early post-traumatic brain
swelling was mainly due to vascular engorgement and an
increase in blood volume. Cellular swelling (cytotoxic oedema)
was thought to play a minor role.100,101
However, more recent
studies suggest that cytotoxic oedema is the main mechanism
of traumatic brain oedema and that cytotoxic oedema can
develop during the first 24 hours after injury.26,34,35,98
Diffusion-
weighted MRI in patients with severe head injury and early
post-traumatic brain swelling demonstrated high levels of
water content in brain tissue,102
even in those patients without
evidence of ischaemia, indicating that cellular swelling was
predominantly responsible for early post-traumatic brain
swelling. The blood volume was actually reduced after severe
traumatic brain injury. An experimental study with contrast-
enhanced MRI demonstrated a lack of blood–brain barrier
opening during an early phase of rapid brain swelling after
diffuse brain injury, excluding a role for vasogenic oedema in
early post-traumatic brain swelling.103
CEREBRAL HYPERAEMIA (VASCULAR
ENGORGEMENT)
Cerebral vasodilatation or hyperaemia leads to brain swelling as
a result of increased volume in the intravascular compartment.
Such vasodilatation may be the result of the effects of the
initial injury or the result of secondary insults, such as hypoxia,
hypercarbia, hyperthermia or seizures. Vascular engorgement
can also follow an increase in venous pressure as a result of
posture, coughing, straining or high intrathoracic pressure.
DISTRIBUTION OF BRAIN SWELLING
Brain swelling may be focal, unilateral hemispheric or diffuse.
Focal brain swelling This is typically seen around cerebral
contusions and intracerebral haematoma (shown in
Fig. 2.13a). In the initial stages, the swelling may be
predominantly cytotoxic, whereas in the later stages of
the injury, vasogenic oedema also plays an important
role.104,105
Unilateral hemispheric swelling Swelling of an entire
cerebral hemisphere most commonly occurs in association
with an acute SDH (less commonly with an EDH or
without a mass lesion; shown in Fig. 2.15). When such
swelling occurs very rapidly, vascular engorgement may
play a role, although eventually the predominant factor
responsible appears to be cytotoxic oedema.26
Diffuse brain swelling Diffuse brain swelling may develop
after a severe diffuse brain injury or may follow secondary

26. 26 PART II BASIC PRINCIPLES
brain insults, such as hypoxia and hypotension. Diffuse
brain swelling is seen in approximately 17% of children
with severe head injury.105
In most children, such swelling
follows a benign course, unless associated with hypoxia
and hypotension.106
Diffuse brain swelling also occurs in
approximately 12% of adults after severe head injury.106,107
The deleterious effects of brain swelling include increased
ICP, reduced cerebral perfusion, cerebral ischaemia and brain
shift, if asymetrical; these aspects will be discussed further in
Chapter 3 (Harmful Effects of Increased ICP).
Focal Brain Damage Secondary to
Brain Shifts and Herniations
Focal damage may occur secondary to brain shifts and
herniations caused by space-occupying haematomas and brain
swelling. Such damage includes, most importantly, brain stem
compression, focal damage due to compression by brain shifts
and focal areas of ischaemia secondary to compression of
intracranial arteries. These lesions will be described further in
Chapter 3 (Harmful Effects of Increased ICP).
Secondary Brain Insults
Secondary brain insults can occur at any time after the initial
injury as a result of systemic or intracranial pathophysiological
disturbances (Table 2.1).
Secondary Insults due to
Extracranial Causes
Secondary brain damage due to extracranial causes is mostly
preventable (see Table 2.1).
HYPOXIA AND HYPOTENSION
Hypoxia (PaO2
<65 mm Hg, O2
saturation <90%, apnoea or
cyanosis before admission) and hypotension (systolic blood
pressure (SBP) <90 mm Hg in adults) are the most common
extracranial causes of secondary ischaemic brain insults.
Hypotension after acute head injury is most commonly due to
blood loss and should be assumed so until proven otherwise.
However, a small subset of patients has hypotension of
neurogenic origin.108,109
Hypotension may occur at any time after injury, including:
(i) the prehospital period, from the moment of injury to
admission to the Emergency Department; (ii) the early
postinjury period, during management in the Emergency
Department; and (iii) the late postinjury period in the
Intensive Care Unit or in the Head Injury Care Ward. Several
investigations have highlighted the incidence of hypoxia and
hypotension during these different phases and their impact on
the outcome of acute head injury (see Table 2.2).
As noted previously in the section on initial injury and its
progression in this chapter, the injured brain is profoundly
vulnerable to hypotension and hypoxia. Hypotension and
hypoxia also lead to cerebral arteriolar dilatation (hyperaemia),
which, in turn, results in increased ICP.
ANAEMIA
Anaemia (haematocrit less than 30%) reduces the oxygen-
carrying capacity of the blood and can contribute to ischaemic
brain injury.116
HYPERPYREXIA
Each 1°C increase in temperature results in a 10% increase
in oxygen consumption in the brain, thus increasing the
risk of ischaemic brain damage. Pyrexia also causes cerebral
vasodilatation and increases ICP by 3–4 mm Hg for every 1°C
increase in temperature.117
HYPERGLYCAEMIA
The sympathoadrenal response to trauma can result in an
increase in glucose production. There is experimental evidence
that high serum glucose can exacerbate secondary brain injury
by increasing lactic acid production, changing neuronal pH
and increasing the release of excitatory amino acids.118–120
In patients with severe head injury, hyperglycaemia during the
early postinjury period has been shown to be associated with
poor outcome.121
SEIZURES
Seizures can aggravate the neurochemical and metabolic
disturbances in partly damaged brain cells, increase the oxygen
demand of cells and lead to an increase in cerebral blood flow
with the risk of increased ICP.
Table 2.1 Types of secondary brain insults
Extracranial insults Intracranial insults
Hypoxia (PaO2
<60 mm Hg, O2
saturation <90%, apnoea or
cyanosis before admission)
Hypotension (SBP <90 mm Hg for adults)
Hypocapnia, hypercapnia
Acute anaemia (haematocrit <30%)
Hyperpyrexia (temperature >38°C)
Hyponatraemia (serum sodium <130 mmol/L)
Hypoglycaemia, hyperglycaemia
Sepsis
Increased intracranial pressure, brain shifts and herniations
Intracranial haematoma•
Cerebral contusion•
Brain swelling•
Hydrocephalus•
Traumatic vasospasm
Seizures
Intracranial infection
Meningitis•
Brain abscess•
SBP, systolic blood pressure.

27. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 27
Table 2.2 Hypoxia and hypotension after acute head injury
Study Phase Evidence References
131 patients with
severe head injury
Prehospital On admission to Emergency Department
Hypoxia in 27%•
Hypotension in 18%•
110
25 patients with
acute head injury
Prehospital Hypoxia evident in 44%, associated with poor outcome 111
49 patients with
acute head injury
Prehospital Hypoxia in 55%, hypotension in 24%
Threefold increase of poor outcome in hypoxic patients
Hypotension associated with poor outcome
112
The National
Traumatic Coma
Data Bank Study
of 717 patients
with severe head
injury
Prehospital,
early and late
postinjury
phases
Prehospital and Early Post-injury Hypotension in 34.6% of
patients
Late post-injury hypotension in 32%
A single episode of hypotension nearly doubled the risk
of mortality. Patients with untreated hypotension in the
prehospital phase fared worse
Hypotension developed only during treatment in the ICU in
16.3% of patients
109, 113
107 patients with
severe head injury
Early postinjury
phase
Hypotension in 24% of patients
Mortality 65% in hypotensive patients
Even brief episodes of hypotension are associated with poor
outcome
114
81 patients with
severe head injury
Early and late
postinjury
phase (first
24 hours after
injury)
Secondary insults occur mostly in the first 24 hours after
injury
Hypotension is associated with increased mortality
Hypoxia is associated with a longer stay in the ICU
115
ICU, intensive care unit.
Ischaemic Brain Damage
Following Acute Head Injury
Ischaemic brain damage is the predominant pathological
change in patients who die from acute head injury.1,122
The
mechanisms leading to post-traumatic ischaemic brain damage
are listed in Table 2.3.
A global reduction of blood flow can occur within the first
few hours after severe brain injury, which is mostly coupled to
a reduction in the cerebral metabolic rate.2,40,41,122
However, in
approximately 30% of patients with severe head injury, the CBF
is reduced to ischaemic levels (<18 mL/100 g per min).41
It has
been suggested that compromise of the microvasculature is the
most likely cause of early ischaemia in severe head injury.26,124
The role of intravascular microthrombosis in ischaemic brain
damage has already been discussed.
Global ischaemic damage can also result from secondary
insults, such as hypoxia, hypotension, increased ICP (leading
to diminished cerebral perfusion), anaemia, seizures and
hyperthermia, especially in patients in whom the CBF is already
reduced.
MECHANISMS BY WHICH ISCHAEMIA
INFLICTS BRAIN TISSUE DAMAGE
The brain is considered to be dependent on aerobic glycolysis
and, hence, an adequate supply of oxygen and glucose, which
Table 2.3 Causes of ischaemic brain damage in acute injury40–42,123
Global ischaemic damage Focal ischaemic damage
Injury to the microvasculature, intravascular
microthrombosis
Hypoxia, hypotension
Increased ICP
Intracranial haematoma (EDH, SDH, ICH)•
Cerebral contusion•
Brain swelling•
Anaemia
Increased metabolic demands (seizures, hyperthermia)
‘Ischaemic penumbra’ around cerebral contusions
Hemispheric ischaemia (hemisphere underlying acute
SDH)
Brain shifts and herniations leading to focal ischaemic
damage in the:
Uncus, parahippocampal gyrus•
Cingulate gyrus, anterior cerebral artery territory•
Posterior cerebral artery territory•
Brain stem•
Subarachnoid haemorrhage and vasospasm
ICP, intracranial pressure; EDH, extradural haematoma; SDH, subdural haematoma; ICH, intracerebral haematoma.

28. again is dependent on adequate perfusion. The reduction in
the cerebral metabolic rate after severe head injury can protect
the injured brain from reduced blood flow. Although there is
evidence of increased glucose metabolism in the immediate
postinjury period, increasing the potential for ischaemic
damage, other mechanisms may mitigate the deleterious
effects of reduced blood flow. Recent evidence indicates that
lactate released into the extracellular space following glucose
metabolism in the astrocytes and glia may be metabolised
aerobically by the neurones, a phenomenon termed ‘coupled
lactate metabolism’.26,127
However, blood flow reduced below a critical ishaemic
threshold can interfere with energy dependent functions,
such as mitochondrial function, cell membrane integrity,
impairment of energy dependant ionic homeostasis in brain
cells and propagation of deleterious biochemical cascades, in a
manner similar to that occurring in partly damaged cells after
the traumatic injury.26
Cerebral ischaemia results in cerebral vasodilatation and
further increases in ICP, a reduction of cerebral perfusion
pressure and further ischaemia. Brain shifts and herniations
secondary to increased intracranial pressure may also result in
further ischaemic damage.
Patients with mild and moderate head injury who suffer
significant ischaemic insults risk adverse outcomes similar to
those with severe head injury.128
FOCAL ISCHAEMIC LESIONS
Focal ischaemic lesions include: (i) an ischaemic zone around
cerebralcontusionsorandICH;(ii)ischaemiainthehemisphere
underlying an acute SDH (Fig. 2.15); (iii) arterial vascular
territory ischaemia; (iv) venous infarction; and (v) watershed
ischaemia.
Arterial Vascular Territory Ischaemia
Posteriorcerebralarteryterritory Thisisthemostcommon
arterial vascular territory ischaemia involves the posterior
cerebral artery and is secondary to uncal herniation, which
compresses the artery against the tentorial edge, leading to
a distal ischaemic lesion in the occipital lobe.
Anterior cerebral artery territory Less commonly, the
pericallosal branch of the anterior cerebral artery may be
compressed between the herniating cingulate gyrus and
the free edge of the falx cerebri during lateral transtentorial
herniation, resulting in a distal ischaemic lesion, typically
located along the medial aspects of the frontal and parietal
lobes.
Territory of major intracranial vessels An injury to the
extracranial internal carotid artery, such as a dissection,
may manifest as ischaemia predominantly in the middle
cerebral artery territory. Suspicion of such a lesion is an
indication for an angiographic study of the extracranial
vessels.
28 PART II BASIC PRINCIPLES
Venous Infarction
Fractures (especially depressed fractures) overlying a major
venous sinus can lead to sinus thrombosis and areas of
venous infarction. Such infarcts typically appear as irregular
haemorrhages located in the white matter in a non-arterial
distribution.73
With superior sagittal sinus thrombosis,
such areas of haemorrhagic ischaemia may be located in the
parasagittal regions; however, the pattern is quite variable.
Watershed Ischaemia
Severe hypotension in the postinjury period can lead to
ischaemia of the junctional zones (watershed areas) between
the major intracranial vessel territories. These areas are in the
frontal parafalcine region (the watershed between the anterior
and middle cerebral artery territories) and in the parietal
convexity region (the watershed between the middle and
posterior cerebral artery territories).73
Mechanisms Contributing to
Repair of Damage from the
Initial Injury
Intrinsic neuroprotective factors produced by neurones and
glia may play an important role in attenuating the effects of
the initial injury.129
Neurotrophic growth factors, such as nerve
growth factors, brain-derived neurotrophic factor, insulin-
like growth factor, glial-derived neurotrophic factor and
neurotrophic factor 3, may be upregulated by injury and may
aid in recovery. There is experimental evidence that growth
factors protect neurones against insults, such as energy loss and
glutamate or calcium excess.130
Role of Genetic Profile in
Determining the Outcome of
Head Injury
Genetic factors may also play a role in the outcome of head
injury. The apolipoprotein E (ApoE) genotype has been
demonstrated to influence the outcome of head injury.
Apolipoprotein E is thought to mediate protective mechanisms
against secondary oxidative damage to neurones after head
injury. Experimental evidence suggests that ApoE deficiency
may increase vulnerability to increased cerebral cortical lipid
peroxidation and protein nitration.21,130
In neuropathological
studies of patients who die from head injury, deposits of
amyloid β-protein in the cerebral cortex (a pathological marker
of injury severity) have been demonstrated predominantly in
patients with the APOE ε4 allele. It has also been suggested that,
in patients who survive head injury, those with the APOE ε4
genotype are more than twice as likely to have an unfavourable
outcome compared with patients without the APOE ε4
genotype, even when other prognostic factors, such as age,
coma score and CT findings, are taken into account.21,74

29. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 29
SUMMARY
The initial, or primary, injury results from a mechanical
deformation of brain parenchymal cells, axons and the
microvasculature. The processes initiated by this injury
may continue to damage parenchymal cells, axons and
the microvasculature, progressing over several hours or
days. Secondary brain damage in the form of intracranial
haematoma, brain swelling and increased intracranial
pressure can develop during the course of the injury.
Damaged brain tissue is vulnerable to further ischaemic
insults. This vulnerability is most marked in patients
with severe head injury, but extends across the entire
spectrum of head injury severity. Secondary brain
insults, especially hypoxia, hypotension and increased
ICP, can amplify the primary damage and its progression
by causing ischaemic brain damage. The outcome of
a given injury is determined by a complex interaction
between the severity of the initial injury, the pattern of
progression, the deleterious effects of secondary brain
insults and the processes of healing and repair. There is
an increasing recognition of the role of the genetic profile
in influencing the course of these complex, interacting
processes.