HEAD INJURY
Head injuries are a
major cause of morbidity and mortality in the community. Trauma is the third
most common cause of death in the
Pathophysiology of head injury
The management of head injury has been based on the concept of primary
and secondary brain injury. The primary brain injury was defined as the
irreversible pathology sustained at the time of the trauma, whereas the
secondary brain injury has been considered the subsequent or progressive brain
damage that occurs due to an evolving pathology following the injury. It has
been the general contention that the primary injury is irreversible, and
management should be directed at preventing or treating secondary pathology
(such as cerebral swelling, hydrocephalus and intracerebral haematoma).
However, it is now clear that some of the biochemical events associated with
what was considered irreversible brain injury are potentially preventable, or even reversible if treatment is instituted
early enough. The distinction between primary and secondary injury has become
blurred, and the terms, whilst useful concepts, are now becoming obsolete.
Most head injuries result from
blunt trauma, as distinct from a penetrating wound of the skull and brain
caused by missiles or sharp objects. The pathological processes involved in a
head injury are:
• direct
trauma
• cerebral
contusion
• intracerebral
shearing
• cerebral
swelling (oedema)
• intracranial
haemorrhage
• hydrocephalus.
Direct trauma.
Although penetrating injuries produce most of their damage by direct trauma to
the brain this is not the case with blunt injuries, in which the energy from
the impact has a more widespread effect.
Cerebral contusion.
This may occur locally under the position of the impact although it usually
occurs more severely at a distance from the area of impact as a result of a
‘contre-coup’ injury. As the brain is mobile within the cranial cavity the
sudden acceleration/deceleration force will result in the opposite ‘poles’ of
the brain being jammed against the cranial vault. A sudden blow to the back of
the head will cause the temporal lobes to slide across the floor of the middle
cranial fossa and the frontal lobes across the floor of the anterior cranial
fossa, causing contusion on the undersurface of those lobes and to the temporal
and frontal poles of the brain as they strike the sphenoid ridge and frontal
bones, respectively. Cerebral contusion consists of lacerated haemorrhagic
brain, and a ‘burst temporal lobe’ may result when the temporal pole has been
severely injured.
Shearing forces. Intracerebral shearing forces occur as a result of
the differential brain movement following blunt trauma, frequently in
conjunction with a contre-coup type of injury. The rotational acceleration
following injury will cause shear forces that result in petechial haemorrhages
(particularly in the upper brainstem, cerebrum and corpus callosum), and
tearing of axons and myelin sheaths. The early pathological changes consist of
retraction balls or microglial scars, and if the patient lives for a number of
months before death then widespread degeneration of myelin will be apparent at
postmortem.
Cerebral swelling. This occurs following trauma, either in a focal
pattern around an intracerebral haematoma or diffusely throughout the cerebrum
and/or cerebellum. The nature of the pathological processes
are not clearly understood but involve a disturbance of vasomotor tone
causing vasodilatation and cerebral oedema. In addition, cerebral contusion and
petechial haemorrhages will contribute to the brain swelling.
Intracranial haemorrhage. Intracranial haemorrhage
following trauma is discussed in more detail later and may be:
• intracerebral
• subdural
• extradural.
The intracranial haematoma or
cerebral swelling may cause the types of cerebral herniation. The medial
surface of the hemisphere may be pushed under the falx (subfalcine), the uncus
and hippocampal gyrus of the temporal lobe may herniate through the tentorium
causing pressure on the 3rd nerve and midbrain (Fig. 4.1), or there may be a
caudal displacement of the brainstem and/or cerebellum, herniating into the
foramen magnum.
Fig. 4.1 Brain herniations. Alateral supratentorial mass
will cause displacement of the lateral ventricles with: (1) subfalcine herniation of
the cingulate gyrus
below the falx cerebri; (2)
herniation of the uncus into the
tentorial hiatus; (3) caudal displacement of the brainstem. Raised pressure within
the posterior fossa
may cause herniation of the
cerebellar tonsils into the foramen
magnum (4).
Hydrocephalus. This occurs infrequently in the early stages after a head injury. It
may be due to obstruction of the 4th ventricle by blood, swelling in the
posterior fossa, or the result of a traumatic subarachnoid haemorrhage causing
obstruction to the absorption of CSF and resulting in a communicating
hydrocephalus. This latter type of hydrocephalus is an uncommon, but important,
cause of delayed neurological deterioration either in the weeks following the
head injury or some years later
Concussion
Concussion involves an instantaneous loss of consciousness as a result
of trauma. The term ‘concussion’ was introduced by Pare and is derived from the
Latin ‘concutere’ which means to shake. In 1941 Denny-Brown and Russell showed
that concussion was produced by a blow on the cranium when it was free to move
and subsequent studies showed that the acceleration/deceleration of the head
resulted in shear strains, contre-coup injury, petechial and punctate
haemorrhages throughout the brainstem, cerebral hemispheres and corpus
callosum, and neuronal injury, the extent depending on the force of the impact.
The term concussion is not strictly defined with respect to the severity of the
injury. However, a minimum criterion is that the patient will have had a period
of amnesia. The retrograde amnesia of most cerebral concussion is usually short
term, lasting less than 1 day. The initial retrograde amnesia may extend over a
much longer period but it gradually shrinks down. Amore reliable assessment of
the severity of the head injury is the post-traumatic amnesia. If the amnesia
following the head injury lasts more than 1 day then the concussion is regarded
as being severe.
Associated injuries
Cranial nerves
The cranial nerves may be injured
as a result of either direct trauma by the skull fracture, movement of the
brain, or cerebral swelling.
The olfactory nerves.
These are the most commonly affected and this may be as a result of either a
fracture through the anterior cranial fossa, directly affecting the tracts, or
tearing of the delicate nerve rootlets passing through the cribriform plate
caused by the sudden brain movement, particularly from a blow to the back of
the head.
The 8th nerve.
Damage to this nerve is often associated with a fracture of the petrous
temporal bone. Deafness may be conductive, due to a haemotympanum, or
sensorineural as a result of injury to the inner ear or to the nerve itself.
Vertigo and nystagmus are due to vestibular nerve or end-organ damage and
usually resolve within a few months of the injury.
Facial paralysis.
This is usually associated with a fracture through the petrous temporal bone,
although this may only be evident on a highresolution CT scan using the bone
‘window’. It may be either immediate, as a result of direct compression of the
nerve, or delayed, due to bleeding and/or swelling around the nerve.
The 6th cranial nerve. This has a long course from the
brainstem to its entry into Dorello’s canal and the nerve is easily damaged by
torsion or herniation of the brain.
The 3rd nerve. This may also be damaged by direct trauma or by brain herniation, the
herniated uncus of the temporal lobe either impinging on the midbrain or
directly stretching the nerve.
The optic nerve. This is infrequently injured by direct trauma.
Skull fractures
Trauma may result in skull
fractures which are classified as:
• simple—a
linear fracture of the vault
• depressed—when the bone
fragments are depressed beneath the vault
• compound—when
there is a direct communication with the external environment. This may result
from either a laceration over the fracture or a fracture of the base of the
skull which will be compound because there will be a direct connection outside
the vault, usually via the air sinuses.
Scalp
lacerations
The extent of the scalp
laceration does not necessarily indicate the degree of trauma to the underlying
brain.
Other injuries
The most common associated
injuries are to the chest, skeletal and cardiovascular systems.
Initial management of head injury
The key aspects in the management
of patients following head injury involve:
• accurate
clinical assessment of the neurological and other injuries
• determination
of the pathological process involved
• the
concept that a change in the neurological signs indicates a progression or
change in the pathological processes.
Immediate treatment at the site
of the injury involves a rapid restoration and maintenance of an adequate
airway, ventilation, essential circulatory
resuscitation, first aid treatment of other injuries and the urgent transfer of
the patient to hospital. It is essential to avoid hypoxia and hypotension as
these will cause further brain injury.
Clinical
assessment
It is fundamental to the
management of the patient to know of changes in the neurological condition as
soon as possible. It is essential to ascertain the type of accident that caused
the head injury and the time injury occurred. An accurate assessment of the
patient’s initial neurological condition, albeit in non-medical terms, can be
obtained from bystanders at the site of the accident or from the ambulance
officers.
Neurological
examination
An accurate neurological
examination will help to determine the type and position of the pathological
process and provide a baseline for comparison with subsequent examinations.
Although a full neurological examination should be undertaken, special emphasis
should be given to the:
• conscious
state
• pupillary
size and reaction
• focal
neurological signs in the limbs.
The conscious
state
If the patient will respond
verbally an assessment should be made of the retrograde amnesia and
post-traumatic amnesia.
There is a continuum of altered
consciousness between those patients who are alert and respond appropriately to
verbal command and those who are deeply unconscious. The first sign of a
depressed conscious state is drowsiness, at which time the patient may be
easily arousable and orientated in time, place and person. As the level of
consciousness deteriorates the patient will become confused and more drowsy. The term ‘coma’ is generally restricted to
patients who show no response to external stimuli, do not obey commands, are
unable to utter comprehensible words, and do not open their eyes. However, the
use of the words ‘coma’, ‘semicoma’ or ‘stuporose’ should be avoided, as they
convey different meanings to different observers. The assessment is more
accurate and reproducible if either the exact nature of the response is
described or, more simply, the
The
Fig. 4.2 The standard observation chart used
at the Royal Melbourne Hospital and at many major trauma centres. The chart incorporates the
Glasgow coma scale.
Pupillary size
and reaction
Careful evaluation of the pupil
size and response to light is essential at the initial clinical assessment and
during further observation. Raised intracranial pressure causing temporal lobe
herniation will cause compression of the 3rd nerve, resulting in pupillary
dilatation, which nearly always occurs initially on the side of the raised
pressure. The pupil will at first remain reactive to light but subsequently
will become sluggish and then fail to respond to light at all. As the
intracranial pressure increases this same process commences on the
contralateral side. A traumatic mydriasis will also result from direct trauma
to the eye, and the dilated pupil should not be confused with that due to a 3rd cranial nerve palsy.
Disorders of ocular movement occur following head injury as a result of injury to an
extraocular muscle or its nerve supply, or due to disturbance of the conjugate
gaze centres and pathways. A destructive lesion of either a frontal or pontine
gaze centre results in tonic overaction of the opposite frontal–pontine pathway
for horizontal eye movement, causing ipsilateral deviation of the eyes with a
frontal lobe lesion and contralateral gaze deviation with pontine lesions. The
oculocephalic manoeuvre and caloric stimulation are important tests of
functional activity of the brainstem reticular formation.
The oculocephalic response should
only be performed after a cervical spine fracture has been excluded. The head
is raised 30° and rotated from side to side in the horizontal plane. In the
normal response the eyes maintain their position in space by moving opposite to
the rotation of the head. The afferent impulses are from the cervical nerve
roots and the semicircular canals.
Caloric testing should also be
performed with the head elevated 30° so that the horizontal canals are
positioned in the vertical plane. Irrigation with ice-cold water causes
ipsilateral tonic gaze deviation.
Skew deviation involves
divergence of the eyes in the vertical plane and is a sign of a lesion within
the brainstem. Ocular bobbing occurs only after a very severe head injury
resulting in pontine damage.
Focal
neurological signs in the limbs
Neurological examination of the
limbs will assess the tone, power and sensation. A hemiparesis will result from
an injury of the corticospinal tract at any point from the motor cortex to the
spinal cord. Following a severe brain injury the limbs may adopt an abnormal
‘posturing’ attitude. The decerebrate posture consists of the upper limbs
adducted and internally rotated against the trunk, extended at the elbow and
flexed at the wrist and fingers, with the lower limbs adducted, extended at the
hip and knee with the feet plantar flexed. There is a continuum of severity of
brain injury with the decerebrate posturing response being partial and
unilateral and occurring only as a result of a painful stimulus to severe
continuing bilateral decerebrate rigidity. The posture probably results from an
upper brainstem injury. Less frequently, the upper limbs may be flexed,
probably due to the injury predominantly involving the cerebral white matter
and basal ganglia—corresponding to a posture of decortication.
Particular attention must be
given to the patient’s ventilation, blood pressure and pulse. At all times it
is essential that care is taken to ensure the patient’s ventilation is
adequate. Respiratory problems may result either as a direct manifestation of
the severity of the head injury or due to an associated chest injury.
Cheyne–Stokes breathing is due to either intrinsic brainstem damage or raised
intracranial pressure causing pressure and distortion of the brainstem.
Bradycardia and hypertension, the Cushing response, are also both indicative of
brainstem compression due to raised intracranial pressure.
Pyrexia frequently occurs
following a head injury. A temperature lasting for more than 2 days is usually
due to traumatic subarachnoid haemorrhage or may occur in patients with a
severe brainstem injury.
General examination
Careful assessment must be made
of any other injuries. Chest, skeletal, cardiovascular or intraabdominal injury
must be diagnosed and the appropriate management instituted. Hypotension or
hypoxia may aggravate the brain injury, and, if severe, will themselves
cause brain damage.
Radiological
assessment
Following the clinical evaluation
radiological assessment will be essential unless the injury has been minor. The
CT scan will show the macroscopic intracranial injury and should be performed
where:
• there
is loss of consciousness (post-traumatic amnesia) of greater than 10 minutes
• the
patient is persistently drowsy or has a more seriously depressed conscious
state
• there
is persisting nausea or vomiting
• there
are lateralizing neurological signs
• there
is neurological or focal deterioration
• there
is skull fracture
• there
is CSF rhinorrhoea
• there
are associated injuries which will entail prolonged ventilation so that ongoing
neurological assessment is difficult.
The CT scan will clearly show the presence of intracerebral or
extracerebral haematoma, as well as cerebral contusion, oedema and infarction.
Small ‘slit’ ventricles and absence of the basal cisterns will indicate
generalized brain swelling. The indications for a skull X-ray have diminished
since the introduction of the CT scan, especially as the bony vault can be
assessed by the CT scan using the bone ‘windows’. If a CT scan has not been
performed, a skull X-ray is obligatory if there has been any loss of
consciousness or if the mechanism of injury is suggestive of an underlying
fracture.
Cerebral angiography is indicated if a caroticocavernous fistula is
suspected by the presence of a bruit over the orbit or by pulsating proptosis.
Carotid or vertebral angiography will be necessary if arterial dissection is
considered a possibility.
NB Full radiological assessment of
the cervical spine utilizing plain X-ray and CT scan is essential in patients
who have sustained a significant head injury, particularly if there are associated
facial injuries.
Further management of head injury
Following the clinical and
radiological assessment the subsequent management will depend on the
intracranial pathology and the extent of any neurological injury.
Minor head
injury
The patient would be assessed as
described above. Any patient who has suffered a head injury must be observed
for at least 4 hours. The following are the minimal criteria for obligatory CT
scan and admission to hospital:
• loss
of consciousness (post-traumatic amnesia) of greater than 10 minutes
• persistent
drowsiness
• focal
neurological deficits
• skull
fracture
• persisting nausea or vomiting
after 4 hours’ observation
• intracranial
pathology noted on a CT scan
• if the
patient does not have adequate care at home.
The further management of these
patients will be careful observation; the neurological observations should be
recorded on a chart displaying the features of the
• elevation
of the head of the bed 20°
• mild
fluid restriction to 2–2.5 l/day in an adult.
Should the patient’s neurological
state deteriorate an immediate CT scan is essential to re-evaluate the
intracranial pathology; further treatment will depend on the outcome.
Severe head
injury
The management of a patient
following a severe head injury depends on the patient’s neurological state and
the intracranial pathology resulting from the trauma. In general, the following
apply.
1.
The patient has
a clinical assessment and CT scan as described previously.
2.
If the CT scan
shows an intracranial haematoma causing shift of the underlying brain
structures then this should be evacuated immediately.
3.
If there is no
surgical lesion, or following the operation, the management consists of:
(a) Careful observation using a
chart with the
(b) Measures to decrease brain
swelling; these include:
(i) careful management of the airway to ensure
adequate oxygenation and ventilation. Hypercapnia will cause cerebral
vasodilatation and so exacerbate brain swelling
(ii) elevation of the head of the bed 20°
(iii) fluid and electrolyte balance. Maintenance of isotonic fluid
requirements, avoiding dextrose solutions and following resuscitation should be
administered until the patient is able to commence nasogastric feeding. Blood
loss from other injuries should be replaced with colloid or blood and not with
crystalloid solutions. Care should be taken to avoid overhydration, as this
will increase cerebral oedema. Following general injury there is retention of
salt and water and excretion of potassium. The retention of water is usually
greater than the retention of sodium, resulting in mild hyponatraemia.
Following a severe head injury fluid and electrolyte abnormalities may occur
for a variety of reasons. Severe hyponatraemia (sodium less than 130 mmol/l)
may be due to excessive fluid intake or, occasionally, because of inappropriate
excessive secretion of antidiuretic hormone (SIADH). The urine is usually
hypertonic with a high sodium level, probably as a result of suppression of
aldosterone secretion occurring as a response to overhydration and expansion of
the circulating volume.
The term ‘cerebral salt wasting’,
which has been applied to this syndrome, is usually inappropriate. Serum sodium
of less than 125 mmol/l may produce neurological
impairment with depression of conscious state. If due to SIADH the usual
treatment is to restrict fluid intake to 800 ml per day or less. Hypernatraemia
is usually associated with hyperosmolality and often results from inadequate
fluid intake. Other causes are diabetes insipidus, as a result of hypothalamic
injury and excessive use of osmotic agents for control of intracranial
pressure. Excessive administration of some feeding mixtures may lead to
electrolyte abnormalities, particularly when complicated by diarrhoea.
(c) Temperature control—pyrexia may be due to hypothalamic damage or
traumatic subarachnoid haemorrhage. However, infection as a cause of the fever
must be excluded. The most common sites of infection after a head injury are
the respiratory and urinary tracts, particularly if a urinary catheter has been
inserted. If the injury is compound, and especially if there has been a CSF
leak, intracranial infection should be suspected. The temperature can usually
be controlled using tepid sponges, and rectal paracetamol or aspirin.
Chlorpromazine, to abolish the shivering response, should be administered if a
cooling blanket is required. Every attempt should be made to control the
temperature because hyperthermia can elevate the intracranial pressure, will
increase brain and body metabolism and will predispose to seizure activity.
Although hypothermia has been advocated in the management of a severe head
injury no clear-cut benefit has been demonstrated.
(d) Nutrition—during the initial 2–3 days the fluid therapy will include 1.5–2 l of
4–5% dextrose, providing 250–400 calories per day. Proper nutritional support
should be commenced after 3–4 days. Feeding at this stage is best done by
intragastric administration, usually by a nasogastric tube, unless this is
precluded by other injuries. The nasogastric feeding should supply 2500–3000
calories per day with a calorie : nitrogen ratio of
180 : 1. The feeding should commence slowly, with dilute mixtures, and the
stomach should be aspirated regularly to prevent regurgitation and pulmonary
aspiration.
(e) Routine care of the unconscious patient including bowel, bladder and pressure care.
More aggressive methods to
control intracranial pressure are advisable if:
• the
patient’s neurological state continues to deteriorate and the CT scan shows
evidence of cerebral swelling without an intracranial haematoma
• there
is a posturing (decerebrate) response to stimuli
• the
In these patients an intracranial
pressure monitor should be inserted to assess the intracranial pressure as
accurately as possible. A transducer can be placed intraparenchymally via a
twist drill craniostomy. A catheter placed into the ventricle will give an
accurate reading of the intracranial pressure and CSF can be drained to help in
the control of the pressure. However, the disadvantages of an intraventricular
catheter include difficulty of placement if the ventricles are small, possible
injury to the brain during placement and infection resulting in ventriculitis
following prolonged monitoring. A subdural catheter will also give an adequate
measurement of the intracranial pressure but may be difficult to insert
satisfactorily if the brain is swollen, and will tend to block. Extradural
monitors are less accurate, although satisfactory recordings are obtainable
with meticulous placement technique.
An intracranial pressure monitor
will also be useful in patients requiring prolonged sedation and ventilation as
a result of other injuries. Measurement of the intracranial pressure will
provide another useful monitoring parameter and any sustained rise in the
pressure will be an indication for careful reassessment and, if necessary, CT
scan.
Following the insertion of the
intracranial pressure monitor the patient will be transferred to the intensive
care department. The techniques used to control intracranial pressure are as
follows.
• Controlled ventilation,
maintaining PaCO2 at 30–35 mmHg. Reduction of the PaCO2 will reduce cerebral
vasodilatation and consequently decrease the intracranial pressure.
• If the pressure remains
elevated despite hyperventilation CSF can be drained from a ventricular
catheter if this has been inserted.
• Diuretic therapy utilizing
intermittent administration of mannitol or frusemide (furosemide) can be used
if the preceding techniques have failed to control the intracranial pressure.
Mannitol is an osmotic diuretic and may also exert its effect by increasing
serum osmolality and drawing water out of the brain. The usual dose is 0.5–1.0
g/kg. The serum osmolality should not exceed 320 mosmol/kg.
• Barbiturate therapy can be
considered if the intracranial pressure is resistant to treatment with the
above techniques. Pentobarbitone (thiopentone) when given as a bolus dose (3–5
mg/kg) is frequently effective in temporarily reducing the intracranial
pressure. There is probably little value in using barbiturate infusion at a
dose to control burst suppression on EEG, although it has been postulated that
this provides brain protection by reducing cerebral metabolism.
• Steroids. Although steroids
dramatically reduce the oedema around cerebral tumours they have little effect
in controlling the brain swelling following a head injury. Steroid medication
is no longer considered advisable as there is no proven benefit for the patient
and possible complications, such as gastrointestinal bleeding, poor wound
healing and infection, may result from their administration.
• Hypothermia. In some centres
hypothermia (to reduce cerebral metabolism and intracranial pressure) has been
advocated, with cooling the patient to
• Hyperbaric oxygen has been used
in the past, but without proven benefit.
Decompressive craniotomy involving removal of a large area of cranial
vault from the frontal and temporal regions bilaterally has been advocated as a
means of controlling raised intracranial pressure due to severe cerebral
swelling following a head injury. The technique is controversial, but it needs
to be performed early following the injury if it is to have a chance of being
of benefit to the patient. At present there are no clinical trials proving its
efficacy in head injury.
There is some controversy concerning the effectiveness of the more
aggressive techniques to treat patients with severe head injuries. If a patient
has suffered a profound brain injury and the neurological examination shows
little or no remaining brainstem function then it is obvious that the
aggressive techniques will provide no benefit and only delay the inevitable.
Similarly, there are some patients who have suffered a severe head injury and
whose intracranial pressure continues to rise despite all the above techniques.
Other patients will have a fatal brain injury without any substantial
rise in intracranial pressure, usually when the brainstem has been the primary
site of injury. However, about 30% of patients who have suffered a severe brain
injury will obtain substantial benefit from control of the intracranial
pressure. Clinical studies have not yet conclusively proven the value of
intracranial pressure control in reducing morbidity following a brain injury as
it is thought that the patients in the studies that were performed were
overventilated and the cerebral blood flow might have been compromised. There is
now consensus that a reduction in raised intracranial pressure will not only
decrease the mortality but will improve the quality of the patient’s outcome
after a severe head injury.
Cerebral perfusion pressure is a vital physiological parameter in the management
of severely head injured patients. The cerebral perfusion pressure—mean arterial BP minus mean intracranial pressure—should be
maintained above 70 mmHg. Consequently head injury management involves ensuring
that the arterial blood pressure is maintained whilst the intracranial pressure
is reduced. This often involves close cooperation between the neurosurgeon and
the intensive care physician.
Management of associated
conditions
Scalp injury
Scalp injuries may include:
• abrasion
• confusion
• laceration
• subgaleal
haematoma.
A large scalp laceration may
result in considerable blood loss. When the patient arrives in the emergency
department ‘spurting’ arteries should be controlled with haemostatic clips
prior to the application of a sterile bandage to the head. The extent of the
soft tissue scalp injury may not reflect the severity of the underlying brain
injury. The principles of management are similar to those of soft tissue injury
at other sites of the body and the wound should be closed without delay. The
hair should be shaved widely around the wound, which should be meticulously
cleaned and debrided. The closure should be performed in two layers if
possible, with careful apposition of the galea prior to closing the skin. The
skin sutures should approximate the cut edges of the skin and care should be
taken to avoid excessive tension which would cause skin necrosis and wound
breakdown.
Straightforward, clean scalp
lacerations can nearly always be closed with local anaesthetic infiltration.
However, if the scalp wound has resulted in loss of soft tissue the wound may
need to be extended to provide an extra ‘flap’ of healthy tissue so that the
skin edges can be approximated without tension.
Skull fractures
Simple linear fracture. There is no specific management
for a simple skull fracture that is undisplaced without an overlying skin
injury.
However, the presence of a
fracture is an indication that the trauma was not trivial and it should provide
a warning that a haematoma may develop beneath the fracture. The patient should
be admitted for observation and CT scan performed.
Compound fracture. A skull fracture may be compound either because of an
overlying scalp laceration or if it involves an air sinus. The scalp wound
should be debrided and closed as described above. A short course of
prophylactic antibiotics should be administered to reduce the risk of
infection.
Depressed skull
fracture
(Fig. 4.3). A skull vault fracture is considered to be significantly depressed
if the inner table fragments are depressed by at least the thickness of the
skull. About half the injuries are due to road trauma and most of the remainder
are due either to objects falling on the head at work
or to assault with a heavy, blunt instrument. A depressed fracture caused by a
non-missile injury usually causes only focal brain damage, so that many
patients never lose consciousness. If the underlying injured brain is an
eloquent area the patient will exhibit focal neurological signs. Haemorrhage
from the bony edges, the dura or underlying brain trauma may result in an
intracranial haematoma which will cause progressive neurological deterioration.
If the depressed fracture is compound and the dura has been lacerated there is
a significantly increased risk of intracranial infection.
Fig. 4.3 Depressed skull
fracture.
If the depressed skull fracture
is compound, prophylactic antibiotics and tetanus prophylaxis should be
administered and surgery, usually requiring a general anaesthetic, should be
performed as soon as possible. A preoperative CT scan will show not only the
position of the depressed skull fragments but also the presence of any
underlying intracranial pathology (Figs 4.4 and 4.5). At operation the scalp
wound should be cleaned and debrided, as described previously,
and the bone fragments elevated. If the dura has been penetrated, or if bone
fragments and external foreign material have been driven down into the brain,
this must be meticulously debrided and haemostasis obtained. It is desirable
that the dura should be closed and this may require the use of a patch of
pericranium or fascia lata from the thigh. If the wound and bone fragments are
heavily contaminated, and particularly if there has been some delay in surgery,
the bone should not be replaced and a reconstructive cranioplasty may be
necessary later. If the depressed fracture is closed there is no urgency in
elevating the bone fragments, provided there is no underlying intracranial
complication. There is controversy over whether a depressed fragment might lead
to epilepsy due to continued pressure on the brain. In general, the depressed
fragments should be elevated if:
• careful studies using the bone
‘windows’ on the CT scan show that the dura might have been penetrated
• there
is significant brain compression
• the
fracture is compound
• there
are cosmetic considerations such as a frontal fracture in a young child.
Fig. 4.4 Depressed skull fracture
with underlying brain contusion.
Fig. 4.5 CT showing severe trauma resulting in
multiple fractures, disruption of the orbit, intracranial contusions involving
the right temporal lobe and intracranial air.
The risk of epilepsy following a depressed fracture is 15% for the whole
group, but the risk ranges from 3 to 70% depending upon other associated
intracranial pathology resulting from the injury. Prophylactic anticonvulsant
medication should be continued for 1 year if the dura has been penetrated.
Cerebrospinal
fluid rhinorrhoea
A fracture involving the base of
the anterior cranial fossa may cause tearing of the basal dura resulting in a
fistula into the frontal, ethmoid or sphenoid sinuses (Fig. 4.6). This type of
fistulous connection should also be suspected if the patient suffers from an
episode of meningitis or if the radiological investigations show a fracture in
the appropriate site. An intracranial aerocele (Fig. 4.7) is proof of a
fistulous connection. CSF rhinorrhoea may also occur as a result of a fistula
through the tegmen tympani into the cavity of the middle ear, and may leak via
the eustachian tube. Base of skull fractures are relatively frequent as skull
fractures are often directed into the skull base by its bony buttresses. They
are often occult radiologically but diagnosed clinically. Anterior fossa
fractures may open into the frontal, sphenoid or ethmoid sinuses, often running
across the cribriform plate. They present with:
• subconjunctival
haemorrhages extending to the posterior limits of the sclera. Periorbital
haematomas or ‘racoon eyes’ indicate subgaleal haemorrhage and not necessarily
a base of skull fracture
• anosmia
• nasal
tip paraesthesiae due to anterior ethmoidal nerve injury.
Middle fossa fractures involving
the petrous temporal bone present with:
• CSF otorrhoea (or rhinorrhoea)
via the eustachian tube
• deafness
due to 8th nerve injury or ossicular disruption
• haemotympanum
•
• 7th nerve palsy—often delayed.
Fig. 4.6 Relationship of base of
skull to air sinuses.
The diagnosis of CSF rhinorrhoea may be difficult. In the early stages
following a head injury
involving fractures to the facial bones,
CSF needs to be differentiated from a bloody nasal discharge.
Allergic rhinitis is the major differential diagnosis in patients
presenting weeks or months after a head injury. Testing for sugar or
B2-transferrin in the nasal discharge may help to identify the fluid as being
CSF. CSF isotope scans using technetium-99 injected through the lumbar theca
are only likely to be positive if there is a large leak. High-resolution CT
scanning following the administration of intracisternal contrast may help to
identify the position of the hole. The major concern of a dural fistula is the
risk of intracranial infection, particularly bacterial meningitis. ACSF leak may
not become apparent for a few days after the head injury, but as the brain
swelling decreases the dural tear becomes unplugged. Alternatively, CSF leakage
may cease due to a brain hernia ‘plugging’ the hole in the dura and bone.
Although the brain hernia might stop the CSF escaping it will not provide
protection against future intracranial infection, as the dural defect will
remain.
There is controversy concerning
the indications for an anterior cranial fossa exploration and dural repair, but
there is general agreement that surgery should be performed if:
• CSF leakage continues for more
than 5 days, indicating the fistula is not trivial
• there
is an intracranial aerocele
• there
has been an episode of meningitis in a patient with a fracture of the anterior
cranial fossa.
Patients with a possible dural
fistula should be placed on prophylactic antibiotic medication. In general,
penicillin is recommended as Pneumococcus is the most common organism;
amoxycillin is appropriate in children due to the risk of Haemophilus
infection. Broad-spectrum antibiotics may lead to the development of resistant
organisms and should be avoided. Nasal swabs may indicate the need for more
individualized antibiotic prophylaxis.
It is best to delay surgery for about 2 weeks, until the initial brain
swelling has resolved. Early surgery, using a craniofacial type of exposure,
has been advocated by some neurosurgeons if there are associated major facial
and anterior vault fractures. However, early surgery may result in further damage
to an already swollen frontal lobe during the retraction necessary to obtain
adequate exposure of the dural tear. The operative procedure involves a frontal
craniotomy with repair of the dural defect using either pericranium or fascia
lata taken from the thigh.
Cerebrospinal
fluid otorrhoea
CSF otorrhoea may occur as a
result of a base of skull fracture involving the petrous temporal bone. Unlike
fractures of the anterior cranial fossa the leakage nearly always settles and
the fistula does not usually provide a route of infection, unless there is
evidence of chronic middle ear infection. Occasionally, a persistent leak may
require surgical exploration and repair.
Fig. 4.7 CT scan
showing intracranial air in a subarachnoid space and within the lateral
ventricles.
Cranial nerve injuries
Injuries to the cranial nerves occurring directly as a result of the
trauma are not helped by surgery. Steroid medication is appropriate for
patients with a delayed facial nerve palsy following fracture of the petrous
temporal bone. Some otologists recommend surgical decompression of the facial
nerve when the palsy is delayed but, as the facial function nearly always recovers, operative intervention is usually not justified.
Missile injuries
Although most literature on missile injuries is related to warfare,
these injuries are unfortunately becoming more common in civilian conflict,
particularly as a result of the increased availability of firearms. In general
the cranial injury is directly proportional to the velocity of the missile. The
‘high-velocity’ injury is defined as resulting from a missile travelling faster
than the speed of sound (1050 ft/s), and modern rifle bullets have a muzzle
velocity greater than 3000 ft/s.
There are three categories of
missile injury:
• tangential—the
missile does not enter the cranium but causes a depressed skull fracture,
lacerating the scalp with an underlying cortical contusion, laceration or
haematomas
• penetrating—the missile enters
the cranium resulting in the deposition of metal, bone fragments and debris
within the brain
• through-and-through—the
missile enters and exits the cranium, frequently creating more than one tract
due to fragmentation
The cranial injury is directly related to the velocity of the missile.
The energy dissipated by the missile equals MV2 where M is the mass
and V the velocity of the missile. Modern ballistics has designed missiles to
have maximal velocity and stability in flight with maximal dissipation of
energy upon impact. The primary missile frequently fragments and can cause
further secondary missiles from fragments of bone or metal.
The missile causes cerebral
damage via three mechanisms:
• mechanical
laceration of brain tissue during transit
• the
shock wave promulgated ahead of the missile
• cavitation
in the wake of the missile.
The pathological processes involve scalp injury, depressed skull
fracture, intracranial haemorrhage and the intracranial pathological sequelae
resulting from a ‘closed’ head injury, including cerebral contusion,
haemorrhage, swelling and raised intracranial
pressure. The pattern of injury will depend on the velocity of the weapon and
the trajectory of the missile through the bone and brain. A high-velocity wound
may result in a rapid increase of intracranial pressure of more than 3000 mmHg
due to the temporary cavity about the missile, which might be 50 times as large
as the missile itself. The high intracranial pressure resulting from the
cavitation may result in death from failure of the respiratory and cardiac centres
in the brainstem.
Management
Rapid transport of the patient to
hospital and urgent treatment is of paramount importance. The early definitive
treatment resulting from prompt transport and the introduction of antibiotics
were the major factors in lowering mortality from head wounds in the Korean and
The operation is performed under
general anaesthesia and intravenous diuretic therapy is administered to reduce
intracranial pressure. A large scalp flap is designed, with excision and
debridement of the entry and exit wounds. Meticulous care is taken to remove
any accessible bone or metallic fragments. Haematoma and necrotic brain debris
are excised. A watertight dural closure should be performed and the scalp
should be closed in two layers (galea and skin). Following surgery, a repeat CT
scan will identify any further retained bone or metallic fragments. Accessible
fragments should be removed, but isolated deep or inaccessible bone or metallic
fragments are probably best left as further neurological damage may occur
during an attempt at excision of these particles. In civilian practice,
infection is unlikely if exploration has taken place within 2 hours of the
injury. In general it is thought that retained metallic fragments have less
potential for infection than other debris. Postoperative management is similar
to that described for severe head injury, with particular attention to
controlling intracranial pressure. Prophylactic antibiotics and anticonvulsant
medication are administered.
Non-accidental head injury
The infantile chronic subdural haematoma or effusion is a distinct
clinical entity. Birth trauma is a frequent cause but in many cases a past
history is inadequate to establish the nature of the injury with certainty.
Chronic subdural haematomas occur in approximately 20% of battered children.
The violent shaking of the immature brain might be sufficient to rupture
bridging veins or cause shearing at the grey/white interface without evidence
of external trauma. If an inadequate history is provided in such a setting, it
is important to screen for a coagulopathy, examine the fundi for retinal
haemorrhages, arrange a skeletal survey and when appropriate involve a
paediatrician and social services. MRI now plays an important role in
determining the chronicity of cerebral injuries in infants. Collections of
different chronicity, or in unusual locations, should alert the physician to
the possibility of non-accidental injury.
Rehabilitation
Some form of rehabilitation is essential following any significant head
injury. If the injury has been relatively minor then the necessary
rehabilitation may involve only advice and reassurance to the patient and
family. However, rehabilitation following a severe head injury will usually
involve a team of paramedical personnel, including physiotherapists,
occupational therapists, speech therapists and social workers.
The major groups of disabilities
resulting from a head injury are:
• impairment
of motor function—hemiparesis, quadriparesis, ataxia, poor coordination
• speech
disturbances—dysphasia, dysarthria
• impairment
of special senses—vision, hearing
• cognitive
disturbance—memory impairment, intellectual disability, personality change.
The general aims of the
rehabilitation process are:
• in the
initial period, to prevent complications such as contractures of the limbs and
to provide counselling for the family
• to
maximize the neurological recovery by restoring old skills and teaching new
skills—this is usually undertaken in a rehabilitation unit
• retraining for future
employment, if necessary and if possible.
The rehabilitation process should commence as soon as possible after the
head injury and should initially concentrate on preventing complications.
Limb contractures and pressure sores are avoided by frequent patient
turning, physiotherapy and the use of splints. As the neurological state
improves the patient’s rehabilitation will normally be undertaken in a
rehabilitation unit. Orthotic devices will assist hemiplegic patients to walk
and, if they can follow simple instructions, most are able to relearn the
activities of daily living.
The speech therapist may provide valuable assistance for patients with
dysarthria and swallowing difficulties. Formal speech therapy probably does
little to improve global aphasia but it does offer important psychological
support for the patient with a severe communication disorder.
Damage to the non-dominant
hemisphere results in perceptual disturbances, particularly relating to visual
spatial tasks. Although the perceptual problems may resolve with time and
rehabilitation, the problems associated with cognitive disturbances and
alteration of personality may persist. Family counselling and support is
essential to help the relatives understand and cope with these long-term
disabilities.
Intracranial haematomas
Intracranial haematoma formation following head injury is the major
cause of fatal injuries in which death may have been potentially avoidable and
in which many survivors are unnecessarily disabled following head injury due to
a delay in the evacuation of the haematoma. The incidence of intracranial
haematomas and the type of haematoma varies widely depending on the different
admission policies. In general hospitals that receive an unselected series of
patients, the incidence varies between 1 and 5% of all head injuries, while the
incidence will be much higher in specialist neurosurgical centres.
Classification
of traumatic intracranial haematomas
The general classification
depends on the relationship of the haematoma to the dura and brain.
Haematomas can be:
• extradural
• subdural
• intracerebral.
However, many haematomas occupy
more than one of the intracranial sites (Table 5.1).
Extradural haematoma
Extradural haematomas are more likely to occur in the younger age group
as the dura is able to strip more readily off the underlying bone. In patients
under 20 years of age, extradural haematomas account for about two-thirds of
all traumatic intracranial haematomas, but represent less than 5% of haematomas
in patients over the age of 50. Although an extradural haematoma may occur in
the presence of a severe head injury and coexist with a severe primary brain
injury, the important feature of an extradural haematoma is that it may occur
when the injury to the underlying brain is either trivial or negligible.
Distribution of
extradural haematomas
The most common sites for
extradural haematoma are the temporal region followed by the frontal area.
Posterior fossa and parasagittal extradural haematomas are relatively uncommon.
The relative proportions in a consecutive series of 200 cases from The Royal
Melbourne Hospital are shown in Fig. 5.1. In most cases the haemorrhage is from
a torn middle meningeal artery or its branches but haematomas may also develop
from haemorrhage from extradural veins, the superior sagittal sinus, transverse
sinus or posterior meningeal artery, the last two being responsible for the
posterior fossa extradural haematomas. A fracture overlies the haematoma in
nearly all (95%) adults and most (75%) children.
Fig. 5.1 Frequency of sites of
extradural haematomas in The Royal Melbourne Hospital series of 200 consecutive
cases.
Clinical presentation
As previously mentioned, an
extradural haematoma may occur as a result of a severe head injury and the
haematoma will then become manifest as a further deterioration of the
neurological state, particularly with lateralizing features involving a 3rd
nerve palsy (dilatation of the pupil) and progressive hemiparesis.
More frequently the extradural
haematoma occurs following a head injury that has resulted in only a transient
loss of consciousness and in approximately one-quarter of cases there has been
no initial loss of consciousness. In these patients the most important symptoms
are:
• headache
• deteriorating conscious state
• focal
neurological signs (dilating pupil, hemiparesis)
• change
in vital signs (hypertension, bradycardia).
Headache. This is the outstanding initial
symptom in patients who have not lost consciousness or who have regained
consciousness. The headache increases in severity and is followed by vomiting. Deteriorating conscious state.
This is the most important neurological sign, particularly when it develops
after a ‘lucid’ interval. It is essential that the drowsiness that occurs in a
patient following a head injury is not misinterpreted just as the patient
wishing to sleep. It is well to remember the nursery rhyme: It’s raining, it’s
pouring,
The old man is snoring,
He bumped his head and went to
bed,
And couldn’t get up in the
morning.
This is a classic description of
an extradural haematoma leading to drowsiness and death. Focal
neurological signs. These will depend upon the position of the
haematoma. In general, a temporal haematoma will produce a progressive
contralateral spastic hemiparesis and an ipsilateral dilated pupil. Further
progression will result in bilateral spastic limbs, a decerebrate posture and
bilaterally dilated pupils (see Chapter 4, Fig. 4.1). Occasionally the
hemiparesis may initially be ipsilateral, due to compression of the
contralateral crus cerebri of the tentorial edge, but it is rare for the
opposite pupil to be involved first.
Change in vital
signs.
The change in vital signs shows the classic Cushing response to a rise in
intracranial pressure—bradycardia accompanied by an increase in blood pressure.
Disturbances in respiration will develop into a Cheyne–Stokes pattern of breathing.
Extradural haematomas occurring
at other than the temporal position show modifications of this clinical
presentation. Frontal haematomas show evidence of lateralizing signs late in
their evolution, the predominant features being a deterioration of
consciousness and pupil abnormalities. In the posterior fossa the vital signs
tend to be affected early, followed by a change in conscious state. The pupils
and limbs may not be affected until the patient becomes deeply unconscious.
Haematomas in the posterior fossa
may cause sudden respiratory failure.
Radiological
investigations
The CT scan is the radiological
investigation of choice and must be performed urgently if an extradural
haematoma is considered a possibility. The CT scan will show the typical
hyperdense (white) biconvex haematoma (Fig. 5.2) with compression of the
underlying brain and distortion of the lateral ventricle.
Fig. 5.2 Extradural haematoma
with the typical hyperdense biconvex appearance.
Treatment
The treatment of extradural haematoma
is urgent craniotomy with evacuation of the clot. The patient should have an
urgent CT scan as soon as an extradural haematoma is suspected clinically. In
some cases the rate of neurological deterioration may be so rapid that there is
not sufficient time for a CT scan and the patient should be transferred
immediately to the operating theatre. Infusion of mannitol (20% solution, 1
g/kg) or frusemide (20 mg intravenously) may temporarily reduce the
intracranial pressure during the transfer to the operating theatre. If
unconscious, the patient must be intubated and hyperventilated during the
transfer. It is essential that there should be no delay in evacuating the
haematoma. An extradural haematoma is a surgical emergency which will result in
death if not removed promptly.
Operation for extradural haematoma The type of
operation performed will depend on the circumstances in which the patient is
being treated.
1 If a CT scan has been performed and the position of the haematoma is
known, the skin flap will be lifted directly over the haematoma.
2 If the patient’s neurological state is stable or only slowly
progressive and if the surgeon is trained in neurosurgical operations, a formal
craniotomy can be performed over the site of the haematoma.
(a) if the surgeon is inexperienced
(b) if craniotomy instruments are not available
(c) if the rate of neurological deterioration
has been so rapid that time has not permitted a CT scan to be performed.
Fig. 5.3 Emergency surgery for
suspected extradural haematoma. (a) Position of exploratory burr holes. (b) If
haematoma found in the temporal position the skin wound is extended. (c)
Further bone removed to enable complete evacuation of haematoma and
haemostasis.
Exploratory burr holes should be
inserted first in the temporal region and then in the frontal and parietal
areas (Fig. 5.3). When the haematoma is identified the burr hole
incision should be extended and the bone over the region of the haematoma
should be rapidly removed. If the haematoma is not found on the first side that
is explored burr holes should be performed in the same order on the other side.
The following are guidelines for the position of the haematoma if a CT scan has
not been performed:
(i) it
underlies the fracture (that may have been seen on the skull X-ray)
(ii) it
underlies a boggy swelling on the skull
(iii) it
is on the same side as the pupil that dilated first
(iv) in
85% of cases it is on the contralateral side to the hemiparesis.
Following removal of the bone of
the vault by craniotomy or craniectomy it is easy to evacuate the haematoma.
The original source of the haematoma, usually the bleeding middle meningeal
artery in the temporal haematoma, is controlled by diathermy or with a
haemostatic clip. The haematoma will have stripped away the dura from the inner
table of the vault, often resulting in considerable oozing from the dural
surface. The dura should be opened, if a CT scan has not previously been performed,
to exclude the coexistence of a subdural haematoma. It should then be closed in
a watertight fashion. It is usually advisable to insert a closed-system,
lowpressure extradural drain to evacuate any blood that may continue to ooze.
The postoperative care is similar to that for any other intracranial procedure.
If the neurological state fails to improve following the evacuation of the
haematoma, or if there is further deterioration, another CT scan should be
performed to exclude recurrence of the haematoma formation.
Prognosis.
If the initial head injury has resulted in only a transient loss of
consciousness, the patient should make a full recovery following removal of the
extradural haematoma, provided the haematoma has been evacuated early enough to
prevent permanent neurological disability. The damage caused by an extradural
haematoma is potentially reversible, provided the haematoma is evacuated before
pressure from the blood clot has caused secondary intracranial pathological
effects.
Subdural haematoma
Subdural haematomas have been
classified into acute, subacute and chronic, depending on the time they become
clinically evident following injury:
• acute
subdural haematoma—less than 3 days
• subacute
subdural haematoma—4–14 days
• chronic
subdural haematoma—more than 14 days.
The CT scan enables a further
classification depending on the density of the haematoma relative to the
adjacent brain. An acute subdural haematoma is hyperdense (white) and a chronic
subdural haematoma is hypodense. Between the end of the 1st week and the 3rd
week the subdural haematoma will be isodense with the adjacent brain.
Acute subdural
haematoma
The acute subdural haematoma
frequently results from severe trauma to the head and commonly arises from
cortical lacerations. However, an acute subdural haematoma can result from a
less severe trauma caused by rupture of a bridging vein or focal tear of a
cortical artery, especially if the patient has been anticoagulated for other
medical reasons (e.g. for atrial fibrillation). Cases of spontaneous acute
subdural haematoma have been reported and in these patients it is essential to
exclude a ruptured aneurysm or bleeding diathesis as a cause. Acute subdural
haematomas are bilateral in approximately one-third of cases, in comparison
with less than 3% of extradural haematomas.
An acute subdural haematoma often
presents in the context of a patient with a severe head injury whose
neurological state is either failing to improve or deteriorating. The features
of deteriorating neurological state—decrease in conscious state and/or increase
in lateralizing signs— should raise the possibility of a subdural haematoma.
Fig. 5.4 Acute subdural haematoma causing
marked shift of the lateral ventricle.
The CT scan will show the
characteristic hyperdense haematoma, which is concave towards the brain, with
compression of the underlying brain and distortion of the lateral ventricles
(Fig. 5.4). Over 80% of patients with acute subdural haematomas have a fracture
of either the cranial vault or the base of the skull, which may be evident on
the bone ‘windows’ of the CT scan.
A craniotomy is nearly always
necessary to evacuate an acute subdural haematoma. If the haematoma is liquid
the blood can sometimes be washed out with gentle irrigation through burr
holes. However if bleeding persists a craniotomy will be required for
haemostasis. Chronic subdural haematoma in the adult In
1863, Virchow first proposed chronic inflammation of the meninges as being the
cause of a chronic subdural haematoma. In 1914, Trotter suggested trauma as the
aetiological factor and in 1932 Gardner, and later Zollinger and Gross,
proposed that an osmotic gradient occurred from the breakdown of haemoglobin.
However, it was subsequently shown that the osmolarity of the haematoma did not
change with time and so this theory was abandoned.
Chronic subdural haematoma
can be divided into two major
groups. The first involves patients having suffered a significant,
and often severe head injury. However, in approximately one third of patients
there is no definite history of preceding head trauma. The aetiology of the
subdural haematoma in this non-traumatic group is probably related to rupture
of a fragile bridging vein in a relatively atrophic ‘mobile’ brain. In this
group the majority of patients are over 50 years of age. Shrinkage of the brain
resulting from atrophy allows the brain to become more mobile and increases the
space traversed by the veins bridging between the cortex and the vault. A
relatively trivial injury may result in movement of the brain, like a walnut
inside its shell, with tearing of the bridging vein. Patients who are
anticoagulated are especially prone to develop a subdural haematoma following
relatively minor trauma.
Clinical
presentation
The presence of a chronic
subdural haematoma should be considered if the neurological state of a patient
being treated in hospital for a significant head injury begins to deteriorate.
Alternatively, the patient may present without the history of a significant
head injury in one of three characteristic ways.
1 Raised intracranial pressure
without significant localizing signs. The patient presents with headache,
vomiting and drowsiness and the absence of focal neurological signs, raising
the differential diagnosis of a cerebral neoplasm or chronic subdural
haematoma.
2 Fluctuating drowsiness. The predominant characteristic
is a decline in the level of consciousness and the patient may abruptly become
deeply unconscious.
3 Aprogressive dementia, which
may be misdiagnosed as Alzheimer’s disease. However, the course of the
dementia is usually more rapid and progressive. Focal neurological signs may
develop, particularly a hemiparesis with an extensor plantar response. In up to
20% of cases the hemiparesis may be ipsilateral to the side of the haematoma
due to shift of the brain causing the contralateral crus cerebri to be
compressed by the tentorial edge.
A chronic subdural haematoma will
be diagnosed on the CT scan as a hypodense, extracerebral
collection causing compression of the
underlying, brain (Fig. 5.5). In 25% of cases the haematoma is bilateral (Figs
5.6 and 5.7).
The chronic subdural haematoma
can be drained through burr holes or a craniotomy located over the haematoma.
No attempt should be made to excise all the membrane of the haematoma. As these
haematomas may be multiloculated it is advisable to insert more than one burr
hole and to visualize the underlying brain at each site.
Fig. 5.5 Chronic subdural
haematoma.
The fluid is hypodense compared with the adjacent brain.
Fig. 5.6 Bilateral chronic
subdural haematoma. The collection on the left is not as hypodense, indicating that it is
more recent than the haematoma fluid on the right. It also has a hyperdense
area, indicating more recent haemorrhage.
Fig. 5.7 T1 MRI showing bilateral
chronic subdural haematoma.
The haematoma fluid should be
washed out completely and after the operation it is usually advisable to place
a subdural catheter for further drainage in a closed drainage system. Following
the operation the patient is nursed flat, or even with the head down initially,
to encourage the brain to expand into the haematoma space. Careful attention
should be given to the fluid intake and serum electrolytes. The normal daily
fluid requirements are given (3 l/day in adults) provided there is no clinical
or radiological evidence of brain swelling. The patient should be slightly more
hydrated after this type of operation than other intracranial procedures, in an
attempt to encourage the brain to swell into the previous haematoma space.
However, hyponatraemia is a common occurrence, both prior to and following
surgery, and if the serum sodium decreases to less than 130 mmol/l the fluid
intake should be reduced.
Subdural haematomas in infancy
The infantile chronic subdural haematoma, or effusion, is a distinct
clinical entity. Birth trauma is a frequent cause but in many cases a past
history is inadequate to establish the nature of the injury with certainty.
Chronic subdural haematomas occur in 10% of ‘battered children’ and the violent
shaking of an infant may be sufficient to lacerate bridging cerebral veins
without evidence of external trauma. Subdural bleeding in infants occurs
bilaterally in 85% of cases and is usually over the dorsolateral surfaces of
the frontal and parietal lobes.
The earliest finding in infants with chronic subdural haematomas is
excessive cranial enlargement as the sutures are unfused. The symptoms are
non-specific and usually involve listlessness, irritability and failure to thrive.
The diagnosis will be confirmed by CT scan. Treatment initially involves
aspiration of the fluid but if, after 2 or 3 weeks, repeated taps have failed
to reduce the volume significantly, a shunt may be inserted to drain the fluid
from the subdural space to the peritoneal cavity.
Traumatic
intracerebral haematomas
occur as a result of
a penetrating injury (such as a missile injury) or a depressed skull fracture,
or following a severe head injury. Intracerebral haematoma is frequently
associated with subdural haematoma. The size of the haematoma varies
considerably and multiple haematomas are frequently seen on the CT scan
following a severe head injury. The contre-coup injury described in may be
responsible for a ‘burst’ temporal lobe which results in a large temporal
haematoma associated with subdural blood. An intracerebral haematoma should be
suspected in any patient with a severe head injury or in a patient whose
neurological state is deteriorating.
The CT scan will show the size
and position of the haematomas (Fig. 5.8). It should be noted that traumatic
intracerebral haematomas not infrequently evolve more than 24 hours after the
trauma. Consequently if is essential to repeat a CT scan if the initial scan
performed after the injury was negative but the patient’s neurological state
deteriorates.
Fig. 5.8 Traumatic frontal
intracerebral haematomas resulting from contre-coup injury.
A large intracerebral haematoma
should be evacuated, unless the patient’s neurological state is improving.
Small intracerebral haematomas, particularly if multiple, are not removed but
the clinician must be aware that they may expand and require subsequent
evacuation.
SPINE TRAUMA
Trauma to the spinal
column occurs at an incidence of approximately 2–5 per
100 000 population. Although the majority of spinal injuries do not affect the cord or
spinal roots, about 10% will result in quadriplegia or paraplegia. Adolescent and young
adult males are the most commonly affected group. Most of the serious spinal cord injuries are
a consequence of road traffic accidents (involving cars, motor bikes and bicycles) although there
are other major causes of spinal cord injury, for example water sports, especially diving into shallow
water, and injuries following skiing and horse riding accidents and drunken falls.
Mechanisms of injury
Although severe disruption of the vertebral column usually causes
serious neurological damage, it is not always possible to correlate the degree of bone damage
with spinal cord injury. Minor vertebral column disruption does not usually cause
neurological deficit, but occasionally may be associated with severe neurological injury. The mechanism of
injury will determine the type of vertebral injury and neurological damage.
Trauma may damage the spinal cord by direct compression by bone, ligament or disc, haematoma, interruption
of the vascular supply and/or traction.
The X-rays taken following a potential spinal cord injury show the
vertebral alignment at that time but do not necessarily indicate the amount of disruption that may
have occurred at the moment of injury, or the degree of ligamentous damage. In general the
injuries can be classified by mechanism of the trauma.
Cervical spine
Flexion and flexion–rotation injuries
This is the most frequent type of injury to the cervical spine; C5/6 is
the most common site. Usually, one or both of the posterior facets are subluxed or dislocated
and may be locked in this position. There is extensive posterior ligamentous damage and these
injuries are usually unstable. The spinal cord may be compressed and distracted, sustaining
both direct damage and vascular impairment from involvement of the anastomotic segmental
vessels or feeders and secondary compression from subluxation with or without instability
Compression injuries
The vertebral body is decreased in height and there may be a wedge
compression fracture or a comminuted fracture with the posterior aspect of the body (retropulsed
fragment) encroaching upon the spinal canal. C5/6 is the most common level for this fracture.
The wedge fracture injuries are usually stable because the posterior bony elements and
longitudinal ligaments are intact. However those with a significant retropulsed fragment are likely to
have disruption of the associated ligaments and thus have to be considered unstable. When combined
with a rotation force in flexion, a ‘tear drop’ fracture may occur, with separation of a
small anteroinferior fragment from the vertebral body, and these should also be considered
unstable. Of the patients who do have spinal cord injuries about half have complete neurological deficit
below the level of the lesion, the remainder having incomplete deficit with the most damage
being to the anterior aspect of the cord.
Hyperextension injuries
These injuries are most common in the older age groups and in patients
with degenerative spinal canal stenosis. Bony injury is often not demonstrated and the major damage is
to the anterior longitudinal ligament secondary to hyperextension. Most of the injuries
result in incomplete cord damage resulting from compression of the cord between the
degenerative body and disc anteriorly, and the hypertrophic ligamentum flavum protruding
posteriorly. The injuries are nearly always stable and a central cervical cord syndrome is the most
common neurological impairment.
Thoracolumbar spine
Flexion–rotation injuries
These injuries occur most frequently at the T12/L1 level and result
in anterior dislocation of the T12 on the L1 vertebral body. There is usually disruption of the
posterior longitudinal ligament and posterior bony elements. The inferior vertebral body often sustains an
anterior superior wedge compression fracture. These are unstable injuries which usually
result in complete neurological deficit of either the spinal cord, conus or cauda equina.
Compression injuries
These injuries are common and the vertebral body is decreased in
height. They are usually stable injuries and neurological damage is uncommon.
Hyperextension injury
This is a very uncommon mechanism of injury at the thoracolumbar spine.
It involves rupture of the anterior longitudinal ligament, rupture of the intervertebral disc and
fracture through the involved vertebral body anteriorly. The injuries are unstable and usually cause severe
cord injury.
Chance fractures
This injury needs to be considered in patients who are involved in a
high-speed accident wearing lap belts without a shoulder harness. They sustain a hyperflexion
distraction injury to the thoracolumbar spine. The forward flexion and bending result in two
potential types of injuries, and they can cause a fracture through the spinous process pedicle and
vertebral body (Fig. 16.2a) or a fracture through the end-plate with disruption of the facet joint and
ligamentous structures (Fig. 16.2b). These injuries can easily be missed because of the unusual
radiological findings.They could well be associated with internal injuries, especially
abdominal injuries.
Fig 1. Mechanisms of injury
Open injuries
These may result from stab injuries or gunshot wounds resulting in cord
damage due to the blast injury, vascular damage and/or cord penetration by the missile or bony
fragments.
Types of neurological impairment
Immediately after a severe cord injury there is a state of diminished
excitability of the isolated spinal cord. This is referred to as ‘spinal shock’ or ‘altered reflex
activity’. The transient depression in the segments caudal to the cord lesion is due to sudden withdrawal of a
predominantly facilitating or excitatory influence from supraspinal centres. There is an areflexic
flaccid paralysis. The duration of spinal shock varies: minimal reflex activity may appear
within a period of 3–4 days or may be delayed up to 6–8 weeks, the average duration being 3–4
weeks.
The spinal cord injury is caused by:
• the direct force applied to the cord
• ischaemia due to vascular injury
• secondary haemorrhage in and around the cord.
The degree of neurological injury will be determined by the extent
and severity of these mechanisms.
Complete lesions
The most severe consequence of spinal trauma is complete transverse
myelopathy, in which all neurological function is absent below the level of the lesion, causing
either a paraplegia or quadriplegia, depending on the level. There will also be impairment of
autonomic function including bladder and bowel function.
Motor deficit
Injuries to the spinal cord will result in an upper motor neurone paralysis
characterized by loss of voluntary function, increased muscle tone and hyperreflexia. Injuries
to the lumbar spine causing cauda equina injuries result in lower motor neurone paralysis
characterized by reduced muscle tone, wasting and loss of reflexes. Acombination of upper and lower motor
neurone lesions results from a thoracolumbar injury involving the conus
medullaris and cauda equina.
Sensory deficit
In complete lesions the afferent long tracts carrying the various sensory
modalities are interrupted at the level of the lesion, abolishing sensory appreciation of
pain, temperature, touch and position and tactile discrimination below the lesion. Visceral
sensation is also lost. Sensation may decrease over a few spinal segments before being lost altogether.
Occasionally there is a level of abnormally increased sensation, hyperaesthesia and hyperalgesia at or
just below the lesion.
Autonomic deficit
Vasomotor control. Cervical and high thoracic lesions above the sympathetic
outflow at T5 may cause hypotension. Interruption of the sympathetic splanchnic vasomotor
control will initially cause a severe postural hypotension as a result of impaired venous return.
Temperature control. The patient with a complete spinal lesion will not
have satisfactory thermal regulation as there will be impairment of the autonomic mechanisms for
vasoconstriction and vasodilatation.
Sphincter disturbance
There is impairment of bowel and bladder control; this is
discussed later.
Incomplete lesions
Anterior cervical spinal cord
Acute anterior cervical spinal cord syndrome is due to compression of
the anterior aspect of the cord. This causes damage to the corticospinal and spinothalamic tracts,
with motor paralysis below the level of the lesion and loss of pain, temperature and touch sensation but
relative preservation of light touch, proprioception and position sense, which are carried
in the posterior columns. The exact pathophysiological process causing this syndrome has not
been precisely defined and it may be due either to stretch applied by the attachment of the dentate ligaments
at the equatorial plane of the cord or to ischaemic injury from compromise of the anterior
spinal artery which supplies the anterior two-thirds of the cord (Fig. 16.3c).
Fig. 16.3 (a) Normal cord cross-section. (b) Central cord syndrome. (c)
Anterior spinal artery syndrome. (d) Brown-Séquard syndrome. (e) Posterior column syndrome.
Central spinal cord
Acute central spinal cord syndrome is usually due to a hyperextension
of the cervical spine with compression of the spinal cord between the degenerative
intervertebral disc and osteophyte anteriorly and the thickened ligamentum flavum posteriorly. The cord
damage is located centrally, with the most severe injury to the more centrally lying cervical tracts
which supply the upper limbs. There is disproportionately greater weakness in the upper limbs in
comparison to the lower extremities below the level of the injury. Sensory loss is usually
minimal, although this is variable and frequently occurs in no specific pattern (Fig. 16.3b).
Brown-Séquard syndrome
The Brown-Séquard syndrome results from hemisection of the
spinal cord as from a stab wound, although it infrequently follows a blunt injury. There is
ipsilateral paralysis of the limbs below the level of the lesion with loss of pain, temperature and
touch on the opposite side of the body. The posterior columns will be interrupted ipsilaterally, but as
some fibres cross there is not a great deficit (Fig. 16.3d).
Spinal cord concussion
There may be a transient loss of function from concussion of the spinal
cord. The exact pathological processes involved in spinal cord concussion are not clear but they
are probably similar to those occurring in cerebral concussion, resulting in temporary impairment
of neuronal function. Recovery usually begins within 6 hours and should be detected
within 48 hours.
Management of spinal injuries
As with head injuries, there is little that can be done to repair the
damage caused by the initial injury and therefore the major efforts are directed towards prevention of
further spinal cord injury and the complications resulting from the neurological damage. The general
principles of management are:
• prevention of further injury to the spinal cord
• reduction and stabilization of bony injuries
• prevention of complications resulting from spinal cord injury
• rehabilitation.
Initial treatment
The first aid management of patients with injuries to the spinal
column and spinal cord requires the utmost caution in turning and lifting the patient. The spine
must be handled with great care to avoid inflicting additional damage. Before moving the patient
sufficient help should be available to provide horizontal stability and longitudinal traction.
Spinal flexion must be avoided. Atemporary collar should be applied if the injury is to the
cervical spine. An assessment should be made for other injuries to the chest, abdomen or limbs.
Hypotension and hypoventilation immediately following an acute
traumatic spinal cord injury may not only be life-threatening but may also increase the extent
of neurological impairment. Resuscitation techniques may need to be modified to ensure that
the spine remains stable. Respiratory insufficiency may require oxygen therapy and ventilatory
assistance. Loss of sympathetic tone may result in peripheral vasodilatation with peripheral vascular
pooling and hypotension. Treatment will include the use of intravascular
volume expanders, alphaadrenergic stimulators, intravenous atropine and occasionally the use of
a transvenous pacemaker. There must be careful attention to the body temperature— the spinal patient is
poikilothermic and will tend to assume the temperature of the environment. Body
temperature must be preserved in cold weather and the patient must not be overheated in warm
weather. A nasogastric tube should be passed to avoid problems associated with vomiting due to
gastric stasis and paralytic ileus. A urinary catheter should be passed to prevent the
complications of bladder overdistension, although intermittent catheterization may become preferable
later. Prophylaxis for deep vein thrombosis and subsequent pulmonary embolus should be
commenced as soon as possible using low-dose heparin (5000 units subcutaneously twice
daily) or low molecular weight heparins. Some centres also favour using various types of
compression stockings on the lower limbs.
Radiological investigations
Plain cervical spine X-rays and computerized tomography scan will show the bony
injuries, and magnetic resonance imaging is very helpful in showing the associated
cord, soft tissue and ligamentous pathology (Fig. 16.4). If a cervical spine injury is suspected (in
the absence of neurological signs or symptoms) but the plain X-ray and CT scan show no
abnormality, the X-rays should be carefully repeated in flexion and extension to exclude instability due
to ligamentous damage.
Fig. 16.4 MRI of spinal injury showing the bone damage and cord injury with localized syrinx.
Spinal reduction and stabilization
As soon as the systemic parameters have been stabilized, attention
should be directed to alignment and stabilization of the spine. The use of skeletal traction for
the restoration and/or maintenance of the normal alignment of the spinal column is a time-honoured and
effective treatment. There are various types of cervical traction devices. The spring-loaded tongs
have become popular because of their ease of application and maintenance. The usual
practice is to apply weight to the traction device to a maximum of
Injuries of the thoracolumbar spine can usually be managed
conservatively by postural reduction in bed. The correct posture must be maintained during
positioning on the side, as well as on the back; this is achieved by the appropriate placement of bolsters
and pillows by a turning team.
Indications for surgical intervention
There has been considerable controversy over surgical intervention in
patients with spinal cord injuries. The damage to the spinal cord occurs principally at the time
of the injury and it is not surprising that there has been no evidence to show improved
neurological function from acute operative decompression of the spine. The following are the general
indications for surgical intervention.
1 Progression of neurological deficit is an absolute indication. It requires
emergency intervention if a compressive lesion is demonstrated by either MRI or CT scan.
2 Patients who have a partial neurological injury, with preservation of
some distal neurological function, and who fail to improve should have further radiological
assessment. Surgery should be considered if this shows persisting extrinsic compression of the
spinal cord within the canal (particularly from a herniated cervical disc), a
depressed fractured lamina or an osteophytic bar, although removal of the
compression may not result in any neurological improvement.
3 An open injury from a gunshot or stab wound should be explored to
remove foreign particles, elevate bone spicules and, if possible, repair the dura.
4 The most common indication for operative intervention is to stabilize the
spine. This is usually undertaken:
(a) if there is gross instability, particularly in the presence of an
incomplete neurological lesion
(b) if it has not been possible to reduce locked facets by closed
reduction—posterior reduction and fusion is appropriate
(c) if operative procedures are needed to stabilize the unstable cervical
spine and so avoid prolonged bed rest; these are favoured by many spinal injury units
(Fig. 16.6).
Other treatments for spinal cord injury
Numerous pharmacological agents have been investigated in
experimental laboratory models but as yet there has been no controlled clinical study to show the
usefulness of these agents in spinal cord injury. The reatments include
glucocorticoids, diuretics, local hypothermia, barbiturates and endogenous opiate
agonists. Although there is no proven benefit, some spinal units use glucocorticoids and
osmotic diuretics for the treatment of oedema. The early use of high-dose dexamethasone may be
beneficial, but there is no conclusive proof.
Fig. 16.6 Postoperative X-ray—anterior cervical discectomy and bone and plate fusion.
Further management
Following reduction and immobilization of the fractures the principles
of the continuing care involve the avoidance of potential complications in patients who are
paraplegic or quadriplegic, and early rehabilitation, which commences as soon as the injury is
stabilized.
General care
Careful attention to the general condition and metabolic state is
essential following the injury; patients frequently develop a negative nitrogen balance and may become
anaemic. Urinary tract or other infections will aggravate the metabolic disorders. The patients
and their relatives will require skilled counselling and emotional support during the treatment and
rehabilitation period.
Skin care
Meticulous attention to pressure areas will avoid the development of
pressure sores which would seriously complicate the recovery and rehabilitation of the patient.
Gastrointestinal complications
Paralytic ileus occurs in acute spinal cord paralysis and if this is
unrecognized, the patient is at risk from vomiting and aspirations. Anasogastric tube should be passed in
the initial management of the patient. Acute gastric dilatation may also develop and is also
treated by nasogastric suction. In 3–5% of patients with acute spinal cord injuries acute peptic
ulceration occurs.
Bladder care
Urinary tract problems are a major cause of potential morbidity and
mortality. During the period of spinal shock the areflexic, flaccid paralysis below the level of the
lesion includes bladder function. The patient will develop acute retention with overflow
incontinence and a catheter is required. Reflex activity returns in upper motor neurone lesions as the
phase of spinal shock passes. The spinal micturitional reflex arc is intact in a
lesion above the conus and an autonomic type of bladder results. The
bladder will empty involuntarily as it fills with urine. The capacity may be less than normal, but
there is good voiding pressure capacity. There is no sensation of bladder fullness. In a lower
motor neurone lesion the spinal micturitional reflex is interrupted and an autonomous bladder
results. Bladder function is governed by a myogenic stretch reflex inherent in the detrusor fibres
themselves. This type of dysfunction is characterized by a linear increase in intravesical pressure,
with filling until capacity is reached. Urine may then flow past the sphincter by overflow
incontinence. In a mixed upper and lower motor neurone lesion, such as with a conus medullaris and cauda
equina injury, it is possible to have a flaccid lower motor neurone detrusor and a spastic sphincter,
as well as the reverse. The principles of management of the bladder consist of maintaining
proper bladder drainage to prevent dilatation of the upper urinary tract and renal impairment,
and the treatment of urinary tract infections. Acatheter is passed initiallyand
bladder training is commenced after the period of spinal shock. The details of bladder training and management
depend on whether the neurogenic bladder has resulted from an upper or a lower motor
neurone lesion and on the results of a cystometrogram showing the intravesical volume pressure
relationship.
Limb care
It is essential that the paralysed limbs should be put through their full
range of movements regularly. Physiotherapy, in particular, is essential to prevent contractures
as the tone returns and spasticity develops.
Special
cervical spine injuries
Jefferson’s
fracture
Jefferson described
bilateral fractures of the posterior arch of the atlas from a direct vertical blow to the head in four
patients. The mechanism of the fracture is due to the head pressing down on the spinal column and
the atlas being squeezed between the occipital condyles above and the axis below. The grooves
for the vertebral artery are the sites where the arches of the atlas are weakest, and when
fractures occur at this site bursting fragments are displaced outwards.
Fractures
of the odontoid process
A fracture of the
odontoid process may occur at the tip (type I) through the base of the dens (type II) or at the base and
extend into the adjacent C2 vertebral body (type III). The fractures that occur at the base of the dens
are the most common and may cause disruption of the blood supply to the dens, resulting in
non-union of the fracture (Fig. 16.7).
Many of the odontoid
fractures can be treated by immobilization in a firm brace or halo for 4 months. If there is
non-union and instability a posterior C1/2 fusion will be necessary. Anterior screw internal fixation
of the odontoid fracture has been advocated but is indicated in certain situations.
Fig. 16.7 Fractures of the odontoid process.
Hangman’s
fracture
This fracture is the
avulsion of the laminar arches of C2 with dislocation of the C2 vertebral body on C3. It is the
characteristic lesion resulting from judicial hanging.
Outcome
following spinal cord and roots injury is summarized:
MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS
Brain tumours are responsible for approximately 2% of all
cancer deaths. Central nervous system tumours comprise the most common group of
solid tumours in young patients, accounting for 20% of all paediatric
neoplasms. The overall incidence of brain tumours is 8–10 per 100 000
population per year. The
incidence increases after the 4th decade of life to reach a maximum of 16 per
100 000 per year in the 7th decade.
Aetiology
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Epidemiology
studies have not indicated any particular factor (viral, chemical or traumatic)
that causes brain tumours in humans, although a range of cerebral tumours can
be induced in animals experimentally. There is no genetic predisposition but
chromosome abnormalities have been noted in many CNS tumours
There is no specific evidence linking CNS tumours to environmental
carcinogens, although many chemicals, especially ethyl and methyl nitrosourea
and anthracene derivatives, show carcinogenic activity in animals and produce CNS tumours. Viral induction
of brain tumours has been used in animal models but there is no firm evidence
for viral aetiology in humans. Ahuman polyoma JC virus injected into primates
produces tumours similar to human astrocytomas after an 18-month incubation
period. This type of ‘slow virus’ effect may account for some of the problems
of isolating viruses from human tumours.
Although immunosuppression is known to increase markedly the risk of
primary lymphoma of the brain, particularly in transplant recipients, there is
not the corresponding increased incidence of gliomas.
At present there is considerable conjecture regarding the role of other
possible aetiological agents, including trauma, electromagnetic radiation and
organic solvents but, as yet, there is no convincing evidence to implicate
these as being involved with the development of brain tumours in humans.
The four hallmarks of the
development of a cancer cell are the ability to proliferate, with the
intracellular growth pathways constituitively activated, the evasion of
apoptosis, with the cancer cells having escaped from cell death pathways, the
attraction and induction of new blood vessels(angiogenesis) to supply increased
metabolic activity of tumour cells, and tissue invasion. Each of these are
dependent on ligand–receptor interactions on the cell surface leading to a cascade of cytoplasmic events that
eventually result in differential gene expression.
Molecular biology techniques have enabled the identification of a variety
of alterations in the genome of the tumour cell, including those of brain
tumours. The present concept of oncogenesis involves both the addition of
oncogenes to the genome and the loss of the normally occurring tumour
suppressor genes. Transformation (spontaneous or induced) is a multistep
process requiring both initiation and promotion. Oncogenes encode proteins that
participate in the signal transduction and second messenger systems that
modulate cell metabolism and proliferation. These proteins include both growth
factors and growth factor receptors such as epidermal growth factor receptor,
platelet-derived growth factor, tryosine-specific protein kinases and
guanine-binding proteins.
Tumour suppressor genes are normally present in the genome and act as a
‘brake’ on cell transformation. Mutations in the p53 tumour suppressor gene on
chromosome 17 are the most common gene alteration found to date in tumours and
have been shown to occur in both astrocytomas and meningiomas. The Li–Fraumeni
syndrome is due to a germ line mutation in the
p53 gene with the development of numerous cancers including gliomas,
ependymomas and medulloblastomas.
Glioma
Neuroectodermal tumours arise from
cells derived from neuroectodermal origin. Gliomas comprise the majority of
cerebral tumours and arise from the neuroglial cells. There are four distinct
types of glial cells: astrocytes, oligodendroglia, ependymal cells and
neuroglial precursors. Each of these gives rise to tumours with different
biological and anatomical characteristics. The neuroepithelial origin of
microglia is in question.
The most common gliomas arise from
the astrocytecells which The tumours arising from astrocytes range from the
relatively benign to the highly malignant. The term ‘malignant’ for brain
tumours differs from its usage for systemic tumours. Intrinsic brain tumours
very rarely metastasize (except for medulloblastoma and ependymoma), and
‘malignant’ refers to aggressive biological characteristics and a poor
prognosis.
Classification
There are many classification
systems of brain tumours in general and gliomas in particular. The period of
systematic classification of tumours began in 1846, when Virchow described the
neuroglia and related it to brain tumours. Although Virchow created the term
‘glioma’, these tumours had already been described under other names. In 1926,
Bailey and Cushing described a histogenetic classification system which
compared the predominant cell in the tumours with the embryonal development of
the neuroglia. The comparison with stages of cytogenesis was probably more of a
working hypothesis than an oncological theory for the origin of the tumours’
cells. The theory that gliomas originate from proliferation of cells of varying
degrees of maturity lying dormant in the brain is not generally accepted except
in the case of medulloblastoma, which may arise from a primitive layer in the
cerebellar cortex.
A valuable prognostic system of
subclassification of astrocytoma was described by Kernohan in 1949.
Astrocytomas were graded from I to IV, with Grade IV being the most malignant
and Grade I cytologically, but not necessarily biologically, benign. Ringertz
simplified the four-grade classification of Kernohan into a three-tiered
system; the comparison between the two is shown in Fig. 1. The glioblastoma
multiforme, equivalent to the Kernohan Grade III and IV tumours, is the most
common adult cerebral tumour, accounting for approximately half of all gliomas.
The low-grade gliomas—the astrocytoma, or Grade I or II Kernohan
astrocytoma—account for only 10–15% of astrocytomas.
The World Health Organization (WHO)
classification recognizes four grades of astrocytoma. Grade I is assigned to
the pilocytic astrocytoma which is biologically distinct from the diffuse
astrocytomas, which are classified as astrocytoma (WHO Grade II), anaplastic
astrocytoma (WHO Grade III) and glioblastoma multiforme (WHO Grade IV).
A grading system proposed by
Daumas-Duport and also known as the St Anne–Mayo System assessed the tumours
according to the presence or absence of four morphological features— nuclear
atypia, mitosis, endothelial proliferation, and necrosis—and they are graded
according to the cumulative features score. Grade I tumours have none of the
features, Grade II tumours have one feature, Grade III tumours have two
features and Grade IV tumours have three or four features.
Pathology
Macroscopic changes
An astrocytoma may arise in any part
of the brain, although it usually occurs in the cerebrum in adults and the
cerebellum in children. A low-grade tumour in the cerebral hemispheres invades
diffusely into the brain. The tumour does not have a capsule and there is no
distinct tumour margin. The low-grade gliomas are usually relatively avascular
with a firm fibrous or rubbery consistency. Fine deposits of calcium are
present in 15% of astrocytomas. Occasionally, a low-grade astrocytoma may
invade diffusely throughout the cerebral hemisphere. In contrast, the
macroscopic appearance of a highgrade tumour, the glioblastoma multiforme, is
characterized by a highly vascular tumour margin with necrosis in the centre of
the tumour. Although in certain areas the margin of the tumour may seem to be
macroscopically well defined from the surrounding brain, there are microscopic
nests of tumour cells extending well out into the brain.
Microscopic changes
The histological appearance of the tumour varies with the tumour’s grade. The
low-grade astrocytoma is characterized by an increased cellularity, composed
entirely of astrocytes. Intermediate-grade tumours show nuclear pleomorphism,
mitotic figures are frequent, and there is increased vascularity, as evidenced
by endothelial and adventitial cell proliferation. In the high-grade
astrocytoma very few astrocytes appear normal. There is marked cellular
pleomorphism, extensive endothelial and adventitial cell proliferation and
numerous mitotic figures with extensive necrosis. The major histological
features of glioblastoma multiforme are endothelial proliferation and necrosis.
The anaplastic astrocytoma is characterized by nuclear pleomorphism and
mitoses, which are absent in the astrocytoma.
Clinical presentation
The presenting features can be
classified under:
• raised intracranial pressure
• focal neurological signs
• epilepsy.
The duration of the symptoms and the
progression and evolution of the clinical presentation will depend on the grade
of the tumour—that is, its rate of growth. Apatient presenting with a low-grade
astrocytoma (Grade I or II) may have a history of seizures extending over many
years, antedating the development of progressive neurological signs and raised
intracranial pressure. The tumours may evolve histologically into the more
malignant anaplastic astrocytoma or glioblastoma multiforme. Patients with the
higher-grade tumours present with a shorter history and glioblastoma multiforme
is characterized by a short illness of weeks or a few months.
Raised intracranial pressure is due to the tumour mass,
surrounding cerebral oedema and hydrocephalus due to blockage of the CSF
pathways. The major symptoms are headache, nausea and vomiting, and
drowsiness.
Headache is the most common symptom
in patients with cerebral astrocytoma and occurs in nearly three-quarters of
patients; vomiting occurs in about one-third. The headaches are usually
gradually progressive and although frequently worse on the side of the tumours,
theymay be bitemporal and diffuse. Characteristically, the headache is worse on
waking and improves during the day. Nausea and vomiting occur as the
intracranial pressure increases, and the patient frequently indicates that
vomiting may temporarily relieve the severe headache. Drowsiness, that is, a
deterioration of conscious state, is the most important symptom and sign of
raised intracranial pressure. The extent of impairment of conscious state will
be related to the severity of raised intracranial pressure. An alert patient
with severely raised intracranial pressure may rapidly deteriorate and become
deeply unconscious when there is only a very small further rise in the pressure
within the cranial cavity.
Focal neurological deficits are common in patients presenting
with cerebral gliomas; the nature of the deficit will depend on the position of
the tumour. Patients presenting with tumours
involving the frontal lobes frequently have pseudopsychiatric problems,
personality change and mood disturbance. These changes are particularly
characteristic of the ‘butterfly glioma’, so called because it involves both
frontal lobes by spreading across the corpus callosum, giving it a
characteristic macroscopic (Fig. 4) and CT or MRI appearance. This type of
tumour may also occur posteriorly, with spread across the splenium of the
corpus callosum into both parieto-occipital lobes. Limb paresis results
from interference with the pyramidal tracts, at either a cortical or a
subcortical level, and occurs in just under 50% of patients. Field defects associated with tumours of the
temporal, occipital and parietal lobes are common, but may be evident only on
careful testing. Dysphasia, either expressive or receptive, is a
particularly distressing symptom occurring in patients with tumours involving
the relevant areas of the dominant hemisphere. The particular characteristics
of posterior fossa and brainstem gliomas will be discussed in the following
section on paediatric tumours.
Epileptic seizures are the most frequent initial
symptom in patients with cerebral astrocytoma and occur in 50–75% of all
patients. Tumours adjacent to the cortex are more likely to be associated with
epilepsy than those deep to the cortex and tumours involving the occipital lobe
are less likely to cause epilepsy than those which are more anteriorly placed.
Astrocytomas may produce either generalized or focal seizures; the focal
characteristics will depend on the position within the brain and the cortical
structures involved.
Investigations
Computerized tomography
CT scan or MRI of the brain are the
essential radiological investigations (Figs 5 and 6); an accurate diagnosis can
be made in nearly all tumours. Low-grade gliomas show decreased density on the
CT scan; this does not enhance with contrast and there is little or no
surrounding oedema. Calcification may be present. High-grade gliomas are
usually large and enhance vividly following intravenous injection of contrast
material (Fig. 7). The enhancement is often patchy and nonuniform and
frequently occurs in a broad, irregular rim around a central area of lower
density. Although tumour cysts may occur in the highgrade tumours, the central
area of low density surrounded by the contrast enhancement is usually due to
tumour necrosis. High-grade tumours are surrounded by marked cerebral oedema
and there is frequently considerable distortion of the lateral ventricles.
Compression of the lateral ventricle in one hemisphere, with pressure extending
across the midline, may result in an obstructive hydrocephalus involving the
opposite lateral ventricle.
Magnetic resonance imaging
When used with gadolinium contrast
enhancement, MRI improves the visualization and anatomical localization of the
tumours (Figs 8
and 9). MRI has the
advantage of being more sensitive than CT scan, enabling the detection of small
tumours and particularly low-grade gliomas that might be missed by CT scan. MRI
provides better anatomical detail and is more useful in visualizing skull base,
posterior fossa and brainstem tumours.
Low-grade astrocytomas may show up
on MRI as abnormal areas of increased T2 signal and decreased T1 signal, even
if the CT scan was normal. High-grade astrocytomas characteristically have low signal intensity on T1-weighted
images and high signal intensity on T2-weighted images. Gadolinium enhancement
is more likely to occur in the higher-grade tumour.
Perfusion-weighted MRI is used to determine the regional cerebral blood
volume, which is increased in high-grade glioma and may be of value in
differentiating recurrent tumour from radiation necrosis. Magnetic resonance
spectroscopy (MRS) is a non-invasive technique that provides information on the
composition and spatial distribution of cellular metabolites. On proton MRS,
tumours have an increased lactate production, loss of N-acetyl aspartate (due
to loss of neurones in the tumour area) and increased choline levels (due to
active membrane biosynthesis).
Fig. 5 Low-grade astrocytoma.
Fig. 6 MRI showing low-grade glioma
Fig. 7 Glioblastoma multiforme
Cerebral angiography
This was the standard study in most patients with astrocytomas prior to the
introduction of CT. It provides helpful information on the vascular supply of
the tumours but is now only rarely indicated.
Plain X-rays
Plain X-rays of the skull do not need to be performed as a routine. The
most common abnormality is erosion of the sella turcica due to long-standing
raised intracranial pressure. Radiologically visible calcification is present
in about 8% of patients with astrocyte-derived gliomas.
Management
Following the presumptive diagnosis
of a glioma the management involves:
• surgery
• radiotherapy
• other adjuvant treatments.
Surgery
Surgery is performed with three
principal aims.
• To make a definite diagnosis.
• Tumour reduction to alleviate the
symptoms of raised intracranial pressure.
• Reduction of tumour mass as a
precursor to adjuvant treatments.
The patient is started on
glucocorticoid steroid therapy (e.g. dexamethasone) when presenting with
clinical features of raised intracranial pressure with the aim of decreasing
the cerebral oedema prior to surgery.
The type of operation performed will
largely be determined by the position of the tumour and by the patient’s
clinical presentation. In general, the tumour is excised as radically as
possible, provided the surgery will not result in any disabling neurological
deficit. Craniotomy is performed in the position that provides the best access
to the tumour and usually with the aid of a frameless stereotactic system to
aid accuracy of localization. If the tumour has not grown to involve the
cortical surface, a small incision is made in a non-eloquent gyrus or sulcus
and the subcortical brain is divided down to the tumour mass.The tumour is
excised, often with the aid of an ultrasonic aspirator. Occasionally, the
tumour may involve one of the ‘poles’ of the hemisphere and the excision may
entail a partial lobectomy.
Although a craniotomy with radical
tumour excision will alleviate the symptoms of raised intracranial pressure,
there has been controversy as to whether a radical resection improves survival.
Most high-grade gliomas weigh approximately
Alternatively, a biopsy, which can
be performed most accurately using stereotactic methods, may be undertaken to
obtain the definite histological diagnosis, without macroscopic tumour
excision, if:
• the tumour is small and deep
seated
• the tumour is diffuse, without
major features of raised intracranial pressure, and macroscopic resection is
not feasible
• the tumour involves highly
eloquent areas (e.g. speech centre) without pronounced features of raised
intracranial pressure.
Stereotactic biopsy involves localization of the tumour with a stereotactic
frame applied to the head of the patient using the CT scan or MRI. The
three-dimensional coordinates of the tumour are ascertained. The surgeon
chooses the point of entry and the desired path through the brain and a computer
program determines the necessary angles for the biopsy probe and the depth to
the tumour (Fig. 6.10).
Postoperative care
The postoperative management of
astrocytoma involves the routine care of a patient following a craniotomy.
Careful neurological observations are performed, as prompt intervention is
essential if the patient’s neurological state deteriorates as a result of
either increasing cerebral oedema or postoperative haemorrhage. A postoperative
haematoma may occur in the region of the tumour excision or it may be
extracerebral, either subdural or extradural. A CT scan should be performed
urgently if there is neurological deterioration, to determine the exact
pathology. Occasionally, postoperative deterioration may be so rapid as to
require urgent re-exploration of the craniotomy without prior radiological
assessment.
In the initial postoperative period
it is essential to avoid overhydration of the patient so as not to precipitate
cerebral oedema. The patient isnursed with the head of the bed elevated 20°, so
as to promote venous return and reduce intracranial venous pressure. Steroid
medication is usually required in the initial postoperative period and is
gradually decreased over the following
days. The steroids may need to be re-instituted during the course of
radiotherapy. The patient is usually mobilized as soon as possible, if
necessary with the help of a physiotherapist.
Radiation therapy
Postoperative radiation therapy is
generally an effective adjunct to surgery in the treatment of higher-grade
gliomas. It has been shown to double the median survival for high-grade gliomas
to 37 weeks. Radiation treatment is planned to optimize the homogeneity of the
radiation dose throughout the tumour volume selected and to minimize high dose
regions in normal brain transited by the radiation beam. The size of the daily
radiation fraction is related to the incidence of complications and a maximal
daily dose is usually between 1.8 and 2.0 gray. The total radiation dose varies
depending on the tumour type, location and size of field, but for gliomas it is
usually between 45 and 60 gray. Opinion varies regarding the tissue volume that
should be treated for malignant glioma but radiation to the tumour area and a
‘generous volume’ of surrounding brain is now advocated, rather than radiation
to the whole brain. The selection of the proper radiation dose for gliomas is
as controversial. Although increasing the radiation dosage from 50 to 65 gray
does slightly improve survival, the higher dose of radiation therapy,
especially over 65 gray, significantly increases the risk of brain necrosis.
Prognosis
At present there is no satisfactory
treatment for the malignant cerebral glioma—the anaplastic astrocytoma and
glioblastoma multiforme. The median survival following surgery is approximately
17 weeks and when radiation therapy is used as an adjuvant the median survival
is approximately 37 weeks. Chemotherapy for highgrade gliomas has been
disappointing and the best results with surgery, radiation therapy and
chemotherapy consistently show a median survival time of less than 1 year. The
median normal for the low-grade glioma (fibrillary astrocytoma; WHO Grade II,
Daumus–Duport Grades I and II) is approximately 8 years, with most tumours
progressing to a higher grade.
The role of surgery, radiation
therapy and other adjuvant therapies in low-grade gliomas is even less certain
than for the high-grade glioma. The low-grade tumour may remain relatively
quiescent for some years before it either continues to grow slowly or changes
to a more anaplastic tumour with resulting debilitating neurological
deterioration. In general, the same principles for surgical excision apply for
lowgrade gliomas as for high-grade gliomas. However, a number of clinical
studies have shown that patients having a radical excision of a tumour have a
longer 5-year survival than those with a subtotal excision. Radiation therapy
has not been shown to improve the survival in patients with low-grade tumours.
In general, other adjuvant therapies are not used for the treatment of
low-grade astrocytoma, but may be of benefit for oligodendrogliomas.
Other adjuvant therapies
Many different adjuvant therapies have been investigated for the treatment
of glioma. These include the use of new chemotherapeutic agents, new methods of
administering cytotoxic chemicals, immunotherapy, hyperthermia, new techniques
of radiotherapy, photodynamic therapy, and gene therapy.
The lack of effectiveness of the present treatment of gliomas is related to
the biology of the tumour. The most common position for tumour recurrence
following conventional treatment is locally, in the tumour bed, indicating that
treatment has failed in local control. Although light microscopy shows
high-grade gliomas to have a relatively well-defined border with the adjacent
brain, special staining techniques, including monoclonal antibodies, show
malignant cells extending well out into the surrounding brain. It is the
failure to control the growth of these cells that is largely responsible for
the local tumour recurrence. As indicated previously, a good surgical resection
with 90% of the tumour excised would still result in 1010 cells
being present. Effective radiotherapy will result in 1 log (90%) or at the most
2 logs (99%) of cell kill and it is unlikely that subsequent chemotherapy would
reduce remaining tumour cells by more than 90%. Consequently, the effect of
cytoreductive surgery, radiotherapy and chemotherapy would result in
approximately 108 cells remaining; the immune system is unlikely to
be able to cope with a tumour burden of more than 105 cells. It
follows that, for any extra treatment to be effective, whether surgery or
adjuvant therapy, it must provide at least 1 log of cell kill.
Chemotherapy
Conventional chemotherapy has been
disappointing. Many of the chemotherapy agents that are active in vitro,
or in other systemic tumours, have reduced activity in malignant brain tumours,
either by exerting an inherently limited cytotoxic potential on brain tumour
cells or by the inability of the chemotherapeutic agent to reach the cells that
are responsible for the tumour recurrence. A study of brain tumour cell
kinetics of high-grade gliomas shows only a small proportion of the cells
(5–10%) in an active growth phase; this has serious consequences for any cell
cycle-specific cytotoxic agent. Until recently the most commonly used single
agent cytotoxic regime involves administration of nitrosourea compounds. The
high lipid solubility and low ionization of these agents ensures a relatively
effective penetration of the cytotoxic compound into the tumour. Combination
therapy, utilizing many different cytotoxic compounds, has been used in various
trials but none of the combinations has been shown to be more beneficial than
the use of the single nitrosourea.
Temozolomide is an alkylating agent
that can be taken orally, penetrates the CNS and is well tolerated with
predictable myelotoxicity. Clinical studies have shown it to be effective in
about 40% of patients. It is now the initial chemotherapy agent of choice, but
it is usually used at the time of tumour recurrence, rather than as an adjuvant
to surgery.
It has been postulated that a reason
for the lack of effectiveness of chemotherapy is the inability of the cytotoxic
compound to reach the tumour cells which are invading the normal adjacent
brain. This has resulted in new techniques of delivering the cytotoxic agent.
High-dose chemotherapy with bone marrow rescue has largely been abandoned
because of its high morbidity and lack of effectiveness. Techniques of
disrupting the blood–brain barrier have been used before chemotherapy infusion
to improve the delivery of chemotherapeutic agents to tumour cells within the
environment of a normal blood–brain barrier. This has resulted in substantially
increased neurotoxicity to the normal brain without significantly improving
survival. Intracarotid chemotherapy suffers from serious limitations— the
perfusion of the tumour mass is less than expected because most tumours are not
supplied entirely by one carotid artery and ‘streaming’ of the cytotoxic agent
results in very high doses of chemotherapy to small areas, with relative
hypoperfusion in other regions. Complications such as serious retinal damage
and neurotoxicity have further reduced the attractiveness of this technique.
Radiotherapy
Attempts to enhance the effect of radiotherapy have included the use of
radiosensitizers, such as metronidazole and misonidazole, which increase the
radiosensitivity of hypoxic tumour cells without a corresponding increase in
the sensitivity of euoxic cells. However, the clinical trials have shown only a
marginal advantage. The use of interstitial brachytherapy, involving
stereotactically implanted radioactive sources into the tumour, has the
advantage of applying a high dose of radiotherapy to the tumour while sparing
the surrounding brain. However, the clinical trials performed so far have
resulted in a high incidence of radionecrosis to the surrounding brain and
improvements in the technique will need to be devised before this method would
become acceptable. Similarly, stereotactic radiosurgery, that involves
radiation to a very highly focused area, is of limited use as it does not
target the infiltrative tumour cells that are responsible for tumour
recurrence.
Hyperthermia
This has inherent basic limitations as, although cell death occurs at
approximately
Immunotherapy
The possibilities for immunotherapy as an adjuvant treatment have been
investigated for many years. Investigations have included the use of active
immunotherapy techniques and, more recently, the application of adoptive
immunotherapy. This technique involves stimulating peripheral blood lymphocytes
in vitro with human recombinant interleukin-2 to produce lymphokine
activated killer cells (LAK cells) which can be administered in conjunction
with interleukin-2. However, the LAK cells do not cross the blood–brain barrier
and so need to be injected in close proximity to the tumour cells. Recent
studies using this technique have been disappointing.
Photodynamic therapy
This is a technique that offers special advantages as an adjuvant therapy
of malignant brain tumours since it has been shown to be an effective method of
controlling local tumours. The technique involves the selective uptake of
sensitizer into the brain tumour, followed by open or intraoperative
irradiation of the sensitized tumour cells with light of an appropriate
wavelength to activate the sensitizer and selectively destroy the tumour cells. Clinical studies using
this method have shown a favourable trend, although formal phase III studies
have not been undertaken.
Gene therapy
Experimental therapies of glioma at present being investigated involve the
use of retrovirus, adenoviruses or adeno-associated viruses to carry a variety
of gene therapies to the cancer cell. It is hoped that as these treatments are
refined over the next decade they will be useful in the treatment of cerebral
glioma.
Oligodendroglioma
Oligodendrogliomas are responsible
for approximately 5% of all gliomas and occur throughout the adult age group
with a maximal incidence in the 5th decade. The tumour is rare in children.
Pathology
Nearly all oligodendrogliomas occur
above the tentorium; most are located in the cerebral hemispheres and about
half of these are in the frontal lobes. Oligodendrogliomas may project into
either the 3rd or lateral ventricles. Oligodendrogliomas have the same spectrum
of histological appearance as astrocytomas, ranging from very slow growing,
benign tumours to a more rapidly growing, malignant variety with abundant
mitotic figures, endothelial proliferation and foci of necrosis. Calcium
deposits are found by histological examination in up to 90% of
oligodendrogliomas. Unlike the astrocyte group, most oligodendrogliomas are
well differentiated. Not infrequently tumours have mixed histology, with both
oligodendroglial and astroglial features.
Clinical presentation
The presenting features are
essentially the same as for the astrocyte group but, as these tumours are more
likely to be slow growing, epilepsy is common, occurring in 80% of patients and
seen as an initial symptom in 50%. The features of raised intracranial pressure
and focal neurological deficits are each present in approximately one-third of
patients.
As for astrocyte tumours, MRI with
contrast may be beneficial but other investigations are usually unnecessary.
Radiological investigation
CT scanning and MRI are the
fundamental investigations. They will confirm the diagnosis of an intracranial
tumour and in many cases the diagnosis of oligodendroglioma will be highly
probable. Calcification will be present in 90% of cases and over half show
contrast enhancement (Fig. 6.11).
Fig. 6.11 Oligodendroglioma
Treatment and results
Treatment involves:
• surgical resection
• radiotherapy
• other adjuvant treatments.
The standard treatment for
oligodendroglioma has been an aggressive resection of the tumour followed by
radiation therapy, although radiotherapy would now not be given to low-grade
tumours, and utilized only for the
intermediate- or high-grade oligodendroglial tumours. Oligodendrogliomas have
been shown to be more sensitive to chemotherapy than the astrocytoma tumours,
especially if the oligodendrogliomas belong to the group with loss of
heterozygosity OF chromosome 1p or 19q.
The survival of patients depends on
the degree of histological malignancy. Five-year survival rates are between 30
and 50% with a small number of patients living for many years (up to 5% for 20
years). However, many tumours with histological features of oligodendroglioma
also have a component of astrocyte-derived cells, usually anaplastic
astrocytoma, and the tumour behaves biologically and clinically as an
anaplastic astrocytoma rather than an oligodendroglioma.
Recurrent cerebral glioma
As discussed earlier, most
high-grade cerebral gliomas will recur within 1 year of the initial treatment
with surgery and radiotherapy. Lowgrade tumours may either recur as a
continuing progression of the slow growth or, alternatively, the histological
characteristics may alter and the tumour may become more anaplastic and rapidly
growing.
The clinical presentation of a
recurrent tumour will be evidenced by either a progression of the focal
neurological signs or the signs of an increase in the intracranial pressure.
The diagnosis will be confirmed by CT scan or MRI in most cases. The major
differential diagnosis is postradiotherapy radiation necrosis, which may
develop as early as 4 months or as late as 9 years after radiotherapy.
The radiological features of
necrosis are an avascular mass, and the diagnosis may be suspected from the
dose of radiotherapy that has been administered. However, there may be
considerable difficulty in differentiating necrosis from recurrent glioma, and
sometimes an operation is required both for definitive diagnosis and to remove
the mass.
The initial deterioration following
a diagnosis of recurrent glioma can usually be temporarily halted by the use of
steroid medication. The major decision is whether further surgery and other
adjuvant therapy should be undertaken. In general, a further operation
involving debulking of the tumour would be considered if:
• the patient is less than 65 years
old
• there has been a symptom-free
interval of 1 year or more since the first operation
• debilitating irreversible
neurological signs are absent
• the tumour is in an accessible
position and repeat surgery would not result in additional morbidity.
Adjuvant therapies
Adjuvant therapies have limited
benefit for patients with recurrent tumour and, considering the morbidity
involved, may not be indicated. Chemotherapy, utilizing temozolomide
administered orally, has shown to have a temporary benefit in up to 40% of
patients. Other chemotherapy agents, especially the nitrosourea compounds, have
much greater toxicity.
Ependymoma
Ependymomas are glial neoplasms
arising from the ependyma and constitute approximately 5% of all gliomas.
Approximately two-thirds of ependymomas occur in the infratentorial compartment
and most of these present in children, adolescents and young adults. The
supratentorial ependymomas occur mostly in adults.
Pathology
The tumour arises from the ependyma
of the ventricle and, although predominantly intraventricular, the tumour often
invades into the adjacent cerebellum, brainstem or cerebral hemisphere. Fourth
ventricular tumours usually arise from the floor or lateral recess of the 4th
ventricle and they may extend into the subarachnoid space to encase the medulla
or upper cervical spinal cord. Alternatively, the tumour may grow laterally
through the foramen of Luschka and into the cerebellopontine angle. The tumours
are well demarcated, nodular, soft and pale. Calcification is common,
especially in supratentorial ependymomas. There are numerous histological
classification systems of ependymomas, and the World Health Organization
classification divides these tumours into cellular, papillary and clear cell
types of non-anaplastic ependymoma and anaplastic ependymoma.
The myxopapillary variety is a slow-growing distinct variant of ependymoma
that occurs in the cauda equina. In an adult the subependymoma variant may be
encountered as an incidental autopsy finding—a discrete nodular mass based in
the brain’s ventricular surface, particularly the floor or lateral recess of
the 4th ventricle or the septum pellucidum—or it may be large enough to present
clinically. It is usually heavily calcified and is composed of cells with
astrocytic as well as ependymal features.
The papillary and anaplastic varieties of ependymoma are responsible for
the majority of clinically symptomatic ependymomas. The cellularity and
architecture of the ependymomas vary but a diagnostic feature is the presence
of rosettes, and most ependymomas contain areas in which perivascular
pseudorosettes are conspicuously developed. In these formations the blood
vessel is surrounded by an eosinophilic halo composed of the radiating tapering
processes of the cells. Blepharoplasts frequently occur in ependymomas but may
be difficult to visualize. These are tiny intracytoplasmic spherical or
rod-shaped structures which represent the basal bodies of cilia, and are most
frequently encountered in the apical portion of cells that form ependymal
rosettes.
Clinical presentation
Posterior fossa ependymomas
Details will be discussed in the
section on paediatric tumours (p. 91). Patients present with features of raised
intracranial pressure due to hydrocephalus as a result of obstruction of the
4th ventricle, ataxia due to cerebellar involvement, and occasionally features
of brainstem pressure or infiltration.
Supratentorial tumours
Virtually all patients with
supratentorial ependymomas present with features of raised intracranial
pressure, often due to hydrocephalus as a result of obstruction of the CSF
pathways. Ataxia is common and focal neurological deficits may occur due to
involvement of the underlying cerebral hemisphere.
Radiological investigation
The CT scan and MRI will show a
tumour that arises in the ventricle and enhances after administration of
intravenous contrast. Calcification is common in tumours arising from the
lateral ventricles (Fig. 6.12). There is frequently associated hydrocephalus.
In the posterior fossa differentiation from a medulloblastoma may be difficult.
Treatment
The treatment of ependymomas is
initially surgical, with an attempt to perform a radical macroscopic resection
of the tumour. Supratentorial tumours are often very large and may extend
throughout the lateral and 3rd ventricles, but the associated hydrocephalus
makes the excision of the intraventricular portion feasible. However, the
tumour may arise from the ventricular wall in
the region of the basal ganglia and
blend imperceptibly with the underlying cerebral structures so that a complete
excision is not possible. Fourth ventricular tumours can be excised from the
ventricle but microscopic infiltration into the underlying brainstem cannot be
removed surgically.
Postoperative radiation therapy is
advisable and, as these tumours may spread through the CSF pathways, sometimes
whole neuraxis radiation is recommended.
The prognosis is related to the
degree of anaplasia of the tumour and for intratentorial tumours varies from
20% to 50% 5-year survival. The prognosis for the supratentorial tumours is
better, particularly in adults.
Pineal tumours
Tumours arising in the region of the
pineal gland are mostly not of pineal origin, but are generally called
‘pineal’, as they have a similar clinical presentation.
The tumours are relatively uncommon, accounting for 0.5% of all
intracranial tumours.
However, they occur more frequently in Japan and China, where the incidence
is up to 5%. Most tumours make their clinical appearance between 10 and 30
years of age.
Classification
Pineal region tumours are classified
in decreasing frequency as:
• germinoma
• teratoma
• pineocytoma
• pineoblastoma
• miscellaneous
• glioma
• cyst.
Germinoma is the most common pineal
region tumour and is similar in histological appearance to germinoma of the
gonads and mediastinum; it occurs predominantly in males. These tumours may
also arise in the suprasellar region, and synchronous tumours in both the
pineal and suprasellar region occur occasionally. Teratoma is like germinoma;
it also arises from displaced embryonic tissue. The other tumour types occur
less commonly.
Clinical presentation
Patients with pineal tumours present
with:
• raised intracranial pressure
• neurological signs due to focal
compression
• endocrine disturbance.
Raised intracranial pressure. The features of raised intracranial
pressure, such as headaches, drowsiness and papilloedema, are due to
hydrocephalus, which is a result of the tumour occluding the aqueduct of
Sylvius.
Focal compression. Compression of the efferent
cerebellar pathways in the superior cerebellar peduncle results in limb ataxia
and distortion of the quadrigeminal plate, produces limitation of upgaze,
convergence paresis with impairment of reaction of pupils to light and
accommodation (Parinaud’s syndrome), and may result in convergence-retraction nystagmus
on upgaze (Koerber–Salius–Elschnig syndrome).
Endocrine disturbance. Endocrine disturbances are
uncommon but include precocious puberty in 10% of patients, almost invariably
male, and diabetes insipidus in 10%. The endocrine effects can either be due to
direct tumour involvement of the hypothalamus or result from the secondary
effects of hydrocephalus.
Radiological investigations
CT scan and MRI will show a pineal
region tumour and will often suggest the correct pathological diagnosis (Fig.
13). On CT scan, before contrast, a germinoma will be a hyperdense lesion in
the region of the pineal gland infiltrating into the surrounding tissue and
there will be uniform vivid enhancement following intravenous contrast.
Calcification is uncommon. On MRI germinomas are relatively isointense to
normal white matter on T1-weighted images and slightlyhyperintense on
T2-weighted scans. Gadolinium contrast defines the tumour well as germinomas
enhance markedly and homogeneously.
Management
This consists of surgery and
radiotherapy. A ventriculoperitoneal shunt or drainage of CSF by a 3rd
ventriculostomy may be required if the hydrocephalus is severe.
There is controversy over whether the definitive treatment should be an
attempt at surgical excision or radiotherapy. As most of the tumours are
germinomas, and these tumours are very radiosensitive, a course of radiotherapy
can be given as the initial treatment if the radiological appearance is typical
for germinoma. If serial CT scans show the tumour has failed to respond to
radiotherapy then surgery may be necessary. Alternatively, if the features on
the initial CT and MRI scans are atypical, and the lesion does not resemble a
germinoma, exploration of the tumour and surgical excision may be appropriate
as the initial procedure.
The preferred surgical approach is usually by a posterior fossa craniotomy,
above the cerebellum and below the tentorium cerebelli. Alternative
supratentorial surgical exposures include approaching the tumour through the
corpus callosum or by retracting the occipital lobe.
Metastatic tumours
Metastatic tumours are responsible
for approximately 15% of brain tumours in clinical series but up to 30% of
brain tumours reported by pathologists. Approximately 30% of deaths are due
to cancer and
• carcinoma of the lung
• carcinoma of the breast
• metastatic melanoma
• carcinoma of the kidney
• gastrointestinal carcinoma.
In 15% a primary origin is never found. Most metastatic tumours are
multiple and onethird are solitary. In about half of these systemic spread is
not apparent. The incidence of tumours in the cerebrum relative to the
cerebellum is 8 : 1, and most occur in the distribution of the middle cerebral
artery. The size of the tumours may vary considerably if the deposits are
multiple. Metastatic tumours are often surrounded by intense cerebral oedema.
Clinical presentation
The interval between diagnosis of
the primary cancer and cerebral metastases varies considerably. In general,
secondary tumours from carcinoma of the lung present relatively soon after the
initial diagnosis, with a median interval of 5 months. Although cerebral
metastases may present within a few months of the initial diagnosis of
malignant melanoma or carcinoma of the breast, some patients may live many
years (up to 15 years) before an intracranial tumour appears. The presenting
features are similar to those described for other intracranial tumours:
• raised intracranial pressure
• focal neurological signs
• epileptic seizures.
Headache and vomiting, indicative of
raised intracranial pressure, occur in most patients and the presenting history
is usually short, often only a few weeks or months. The increased intracranial
pressure will be caused by either the tumour mass and surrounding oedema or, in
posterior fossa tumours, obstructive hydrocephalus. The pattern of focal
neurological signs will depend on the position of the tumour deposits and the
patient may present with a progressive hemiparesis or speech disturbance with
supratentorial tumours or gait ataxia with cerebellar tumours. Epileptic
seizures occur in approximately 25% of patients and may be either focal or
generalized.
Occasionally, metastases, especially
melanoma or choriocarcinoma, present following an intracerebral haemorrhage.
Radiological investigations
CT scan or MRI will diagnose the
metastatic tumour and will show whether the deposits are solitary or multiple. Most metastatic tumours are relatively
isodense on the unenhanced CT scan and they enhance vividly after intravenous
contrast injection. Tumours that may be hyperdense prior to contrast are
melanoma, choriocarcinoma, mucoid adenocarcinoma (e.g. from the
gastrointestinal tract) and 50% of lymphomas. There is usually considerable
surrounding cerebral oedema with distortion of the ventricular system. MRI
following gadolinium contrast will demonstrate small metastatic tumours often
not visible on the CT scan (Fig. 15).
Treatment
Steroid medication (e.g.
dexamethasone) will control cerebral oedema and should be commenced immediately
if there is raised intracranial pressure.
Surgery to remove the metastasis is
indicated if:
• there is a solitary metastasis in
a surgically accessible position
• there is no systemic spread.
Removal of a solitary secondary is
preferable only if the primary site of origin has been, or will be, controlled.
However, excision of a single metastasis will provide excellent symptomatic
relief and consequently may be indicated even if the primary site cannot be
treated satisfactorily. Surgery is, of course, mandatory if the diagnosis is
uncertain.
Radiotherapy, together with steroid
medication to control cerebral oedema, is used to treat patients with multiple
cerebral metastases and may be advisable following the excision of a single
metastasis. The treatment, up to 45 gray, is usually given in a 2-week course.
Over the past decade stereotactic
radiosurgery utilizing a highly focused beam of radiation has been used to
treat single and multiple cerebral metastases. The therapy does seem to be
effective in some cases and its role relative to surgery is being evaluated.
Anticonvulsant medication is given
both to patients who have suffered epileptic seizures and as a prophylactic measure.
Prognosis
About 30% of patients with solitary
metastatic deposits from carcinoma of the lung or melanoma and 50% of patients
with carcinoma of the breast survive 1 year following surgical excision. In
those patients where the source of the metastatic tumours is undetermined,
about 50% survive 1 year.
Leptomeningeal metastases
Meningeal carcinomatosis is widespread, multifocal seeding of the
leptomeninges by systemic cancer. The clinical presentation includes:
• hydrocephalus, causing headaches and vomiting
• cranial nerve abnormalities due to direct invasion by the tumours
• spinal root involvement due to local infiltration.
The CT scan or MRI findings may be subtle but frequently show excessive
enhancement of the meninges. Lumbar puncture can be performed if there is no
evidence of raised intracranial pressure. Malignant cells may be seen in the
CSF, the protein concentration is increased and the glucose reduced.
Paediatric tumours
Intracranial tumours are the most
common form of solid tumours in childhood, with 40% of the tumours occurring
above the tentorium cerebelli. The most common supratentorial tumours are
astrocytomas, followed by anaplastic astrocytomas and glioblastoma multiforme.
Craniopharyngioma occurs more commonly in children than in adults and is
situated in the suprasellar region. Other, less common, supratentorial tumours include primitive
neuroectodermal tumours (PNETs), ependymomas, ganglioglioma and pineal region
tumours.
Posterior fossa tumours
Sixty per cent of paediatric brain
tumours occur in the posterior fossa. The relative incidence of the tumours is:
1 cerebellar astrocytoma 30%
2 medulloblastoma (infratentorial
primitive neuroectodermal tumour) 30%
3 ependymoma 20%
4 brainstem glioma 10%
5 miscellaneous 10%:
(a) choroid plexus papilloma
(b) haemangioblastoma
(c) epidermoid, dermoid
(d) chordoma.
Clinical presentation
The presenting clinical features of
posterior fossa neoplasms in children are related to:
• raised intracranial pressure
• focal neurological signs.
Raised intracranial pressure
This is the most common presenting
feature. It is due to hydrocephalus caused by obstruction of the 4th ventricle and is manifest by
headaches, vomiting, diplopia and papilloedema. The headaches begin
insidiously, gradually becoming more severe and frequent; they are worst in the
early morning. There is usually no specific headache localization. Vomiting is
frequently associated with the headaches and may temporarily relieve the
headache. Raised intracranial pressure may result in a strabismus causing
diplopia due to stretching of one or both of the 6th (abducens) cranial nerves.
This is a so-called ‘false localizing sign’. Papilloedema is usually present at
the time of diagnosis. In infants, an expanding head size is an additional sign
of raised intracranial pressure.
Focal neurological signs
These are due to the tumour invading
or compressing the cerebellum (nuclei and tracts), the brainstem and cranial
nerves. Truncal and gait ataxia result particularly from midline cerebellar
involvement. Horizontal gaze paretic nystagmus often occurs with tumours around
the 4th ventricle. Upbeat vertical nystagmus is indicative of brainstem
involvement.
Disturbances of bulbar function,
such as difficulty in swallowing with nasal regurgitation of fluid, dysarthria
and impaired palatal and pharyngeal reflexes, result from brainstem
involvement. In addition, compression or tumour invasion of the pyramidal
tracts may result in hemiparesis and, if the ascending sensory pathways are
involved, sensory disturbance will occur in the trunk and limbs.
The tumour may directly envelop the
lower cranial nerves—glossopharyngeal, vagal, spinal accessory and
hypoglossal—as well as the 7th cranial nerve.
Neck stiffness and head tilt may
occur in children with posterior fossa neoplasms, and may be due to herniation
of a cerebellar tonsil or tumour tissue resulting in dural irritation.
Investigations
CT scan and MRI have replaced the
need for the previous radiological investigations that included radio-isotope
brain scanning, air ventriculography and posterior fossa angiography. The CT
scan and/or MRI will show the presence of a posterior fossa tumour, its
position and whether it arises primarily in the brainstem, 4th ventricle or the
cerebellum (Figs 20–24).
Management
The treatment of posterior fossa
tumours involves:
• surgery
• radiotherapy
• chemotherapy.
Apreliminary CSF shunt may need to be performed in a child with severely
raised intracranial pressure due to hydrocephalus. The CSF diversion can be
achieved by either an external drain or a ventriculoperitoneal shunt. An
external drain is a temporary measure only, because of the risk of infection. A
ventriculoperitoneal shunt provides immediate and controlled relief of
intracranial hypertension and the subsequent posterior fossa operation can be
performed as a planned elective procedure, rather than an urgent operation in
suboptimal conditions. A criticism of a preoperative ventriculoperitoneal shunt
is that it might promote the metastatic
spread of tumour. A filtering chamber in the shunt system may lessen this
risk but this predisposes to shunt malfunction.
Steroid medication to control local oedema is commenced preoperatively. The
operation is performed in either the sitting or prone position through a
vertical midline incision. A posterior fossa craniotomy is performed, usually
with excision of the bone down to and around the foramen magnum.
Postoperative care involves careful monitoring of the neurological signs.
Postoperative haemorrhage or oedema may result in rapid deterioration of the
neurological state, and in respiratory arrest. An urgent CT scan may indicate
the cause and site of the problem but the deterioration may be so rapid that
the wound may need to be reopened without the benefit of prior scanning. If a ventriculoperitoneal
shunt has not been inserted prior to tumour removal an exacerbation of the
obstructive hydrocephalus may occur if the tumour excision has failed to
relieve the CSF obstruction. Disturbances of bulbar and lower cranial nerve
function may cause difficulty in swallowing. Nasogastric feeding may be
necessary until the protective mechanisms return, and great care should be
taken to avoid aspiration.
Medulloblastoma
Medulloblastoma, also referred to as
an infratentorial PNET, is a malignant tumour usually arising in the midline
from the cerebellar vermis, although it may occur more laterally in a
cerebellar hemisphere in older patients. The tumour expands to invade the
adjacent cerebellum and large tumours completely fill the 4th ventricle. Fig.20
Presenting features. The presenting features are
related to hydrocephalus and cerebellar dysfunction. Truncal ataxia is
typically present in children with medulloblastoma but cranial nerve deficits,
except for a 6th nerve palsy, are uncommon in the early stages.
Surgery. At surgery the cerebellar vermis
is split in the midline and it is usually possible to obtain a gross
macroscopic excision of the tumour with complete removal from the 4th
ventricle.
Radiation therapy. Medulloblastoma is relatively
radiosensitive and radiation therapy is recommended to the entire neuraxis
because of the tendency of the tumours to seed along the CSF pathways.
Chemotherapy. Adjuvant chemotherapy is usually
recommended Young children are exquisitely sensitive to the neurotoxicity due
to radiation therapy, such that the possibility of utilizing chemotherapy alone
and postponing the use of radiotherapy has been trialled.
Prognosis. Although the combination of
radical surgery and irradiation has improved the prognosis, the 5-year survival
rate is approximately 40%.
Cerebellar astrocytoma
The cerebellar astrocytoma is
frequently a benign, slowly growing cystic tumour which is the most favourable
of all the intracranial paediatric neoplasms. The tumours may arise in either
the hemisphere or vermis and frequently consist of a large tumour cyst with a
relatively small solid component in the wall of the cyst (see Fig. 21). Less frequently the tumour may be
entirely solid with little or no cystic component. Histologically, the solid
portion of the tumour is usually a Grade 1 or 2 astrocytoma.
Presenting features. The clinical presenting features
are similar to those of a medulloblastoma, but as the tumour may be located
more laterally the presenting features are accompanied by ipsilateral
cerebellar disturbance. The duration of symptoms is variable but tends to be
longer than with medulloblastoma, averaging 6–12 months.
Surgery. Acomplete surgical excision is
usually possible and it is only necessary to excise the solid component from
the cystic tumour.
Radiation therapy. Postoperative radiation therapy is
not usually indicated if an excision has been possible. The prognosis is the
most favourable of all intracranial childhood tumours with a cure rate in
excess of 75%.
Ependymoma
The ependymoma of the 4th ventricle
arises from the floor of the 4th ventricle and is attached to, and may
infiltrate, the underlying brainstem
Pathological features and histology are described
earlier.
Presenting features. The presenting features are similar
to those described for a medulloblastoma,although the initial symptoms and
signs are usually due to hydrocephalus. Involvement of the dorsal brainstem
results in unilateral or bilateral facial weakness.
Surgery. The surgical excision of the
ependymoma involves splitting the inferior vermis to obtain access to the 4th
ventricle. It is usually possible to perform a gross macroscopic excision of
the tumour from the ventricle and adjacent cerebellum but, as the tumour often
originates from the floor of the 4th ventricle, total excision is rarely
possible.
Radiation therapy. Postoperative radiation therapy is
usually administered to the posterior fossa and, as the tumour seeds along the
CSF pathways, entire neural axis irradiation is often recommended, particularly
in the higher-grade ependymoma.
There is no definite advantage from
adjuvant chemotherapy, although it may be used at the time of tumour
recurrence.
Brainstem glioma
The brainstem glioma arises
predominantly in the pons, less frequently in the medulla but may infiltrate
extensively throughout the brainstem.
Clinical presentation. The clinical presentation
characteristically includes progressive multiple bilateral cranial nerve
palsies with involvement of pyramidal tracts and ataxia. Facial weakness and
6th cranial nerve palsy are common and an internuclear ophthalmoplegia is
indicative of an intrinsic brainstem lesion. The child’s personality often
changes—they become apathetic. Raised
intracranial pressure is less common
than with other paediatric posterior fossa neoplasms, as obstruction of the 4th
ventricle or aqueduct of Sylvius occurs late in the illness.
The CT and MRI appearance is of an
expanded brainstem. MRI has considerably improved the accuracy of the diagnosis
(Fig. 6.23).
Surgery. Surgical treatment is not usually
indicated, although either an open or a stereotactic biopsy may be performed to
confirm the diagnosis.
Radiation therapy. Palliative radiation therapy is
the only treatment. The tumour usually causes death within 24 months of
diagnosis, although some patients with low-grade tumours will live longer.
Chemotherapy has limited benefit.
BENIGN BRAIN TUMOURS
The benign brain tumours may be intimately associated with, and surrounded
by, the adjacent brain, but the tumour cells do not invade the underlying
brain. This is in contradistinction to the gliomas, which are intrinsic brain
tumours actively invading the adjacent brain.
Meningioma
Meningiomas are the most common of the benign brain tumours and constitute
about 15% of all intracranial tumours, being about one-third of the number of
gliomas. Although they may occur at any age, they reach their peak incidence in
middle age, are very uncommon in children and occur more frequently in women
than men. The term meningioma was introduced by Harvey Cushing in 1922,
although the tumour had been described in the late eighteenth century. The
tumour arises from the arachnoid layer of the meninges, principally the
arachnoid villi and granulations.
Aetiology
As for other brain tumours, no
definite aetiological factor has been identified. However, the possibility that
head trauma predisposes to the development of meningioma has been the subject
of controversy for many years. Although epidemiological studies do not support
trauma as an aetiological factor, there have been cases reporting the
development of meningiomas at the site of substantial meningeal trauma.
Meningiomas are known to occur following low levels of irradiation as was given
in the past for tinea capitis, and an analysis of the Nagasaki atomic bomb
survivors found a high correlation between the incidence of meningiomas and the
distance from the epicentre of the explosion. Meningiomas occur with a high
frequency in patients with neurofibromatosis type 2 (NF2) (often multiple).
This association has prompted cytogenetic studies, which have shown that
monosomy of chromosome 22 is the most common chromosomal abnormality noted in
meningiomas, occurring in 50–80% of sporadic tumours. In addition, alterations
of many other chromosomes (including chromosomes 1, 6, 9, 10, 11, 13, 14, 18
and 19) have been noted to be involved in the formation and progression of
meningioma.
The importance of sex hormones and
their receptors in meningioma is suggested by the 2–4 times incidence in
females. Oestrogen binds in less than 30% of meningiomas, with the majority of
those receptors being type II subtype, that have a lower affinity and
specificity for oestrogen than the classic type I receptor usually found in
breast cancer. Progesterone receptors are much more commonly associated with
meningiomas, occurring in 50–100% of tumours tested.
Position of meningiomas
Meningiomas arise from the arachnoid
layer of the meninges, especially the arachnoid cap cells. The most common
location is in the parasagittal region arising either from the wall of the
superior sagittal sinus (parasagittal) or from the falx (falcine). Less frequently the
tumours may arise from the convexity of the cranial vault, where they are
particularly concentrated in the region of the coronal suture. Sphenoidal ridge
meningiomasare divided into those that arise from the inner part of the lesser
wing of the sphenoid and the adjacent anterior clinoid process, and those
arising from the outer sphenoidal ridge, comprising the greater wing of the
sphenoid and theadjacent pterion (the junction of the temporal, parietal and
frontal bones). Less frequently, the tumours may arise from the olfactory
groove, tuberculum sella (suprasellar), floor of the middle cranial fossa,
cavernous sinus or posterior fossa (Table 7.1). Meningiomas usually occur as a
single intracranial tumour but multiple intracranial meningiomas may present in
NF2.
Pathology
Unlike gliomas, where the
classification system is based on the histological appearance of the tumour, meningiomas
are usually classified according to their position of origin rather than their
histology. The reason for this is that the biological activity of the tumour,
the presenting features, the treatment and prognosis are all related more to
the site of the tumour than to the histology.
The major histological types are
listed below.
• Syncytial or meningotheliomatous—sheets of cells with varying amounts of
stroma.
• The transitional type is characterized by whorls of cells which may
undergo hyalin degeneration with subsequent deposition of calcium salts. These
calcified concentric psammoma bodies form the characteristic feature of
many transitional meningiomas but they may also be present in the syncytial or
fibroblastic types.
• The fibroblastic type contains abundant reticulin and collagen fibres.
• Angiomatous meningiomas are much less common and their characteristic
feature is the predominance of vascular channels separated by sheets of cells.
Histologically, these tumours resemble cerebellar haemangioblastomas.
• Malignant meningiomas occur infrequently. The indications of malignancy
include cellular pleomorphism, necrosis, increased numbers of mitotic figures
and local invasion of brain. Atypical meningiomas are tumours that lack the
histological features of malignancy, but have a biological behaviour
intermediate between the typical and malignant meningioma. These tumours are
most likely to recur.
Clinical presentation
Meningiomas present with features
of:
• raised intracranial pressure
• focal neurological signs
• epilepsy.
The position of the tumour will
determine the features of the clinical presentation. The tumours grow slowly
and there is frequently a long history, often of many years, of symptoms prior
to the diagnosis.
Parasagittal tumours
These tumours most often arise in
the middle third of the vault and the patient may present with focal epilepsy
and paresis, usually affecting the opposite leg and foot as the motor cortex on
the medial aspect of the posterior frontal lobe is affected. Tumours arising
anteriorly are often bilateral and patients present with features of raised
intracranial pressure. As these tumours involve the frontal lobes,
pseudopsychiatric symptoms, as well as impairment of memory, intelligence and
personality, may occur. Urinary incontinence is occasionally a symptom of a
large frontal tumour, especially if it is bilateral. Tumours arising from the
posterior falx may affect the parieto-occipital region and produce a homonymous
hemianopia. If the tumour lies above the calcarine fissure the inferior
quadrant is more affected; when the tumour is below the fissure the upper
quadrant is predominantly affected.
Fig. 7.2 Parasagittal meningioma.
Convexity tumours
Convexity tumours may grow to a
large size if situated in front of the coronal suture. They present with raised
intracranial pressure. More posterior tumours will cause focal neurological
symptoms and focal epilepsy.
Sphenoidal ridge tumours
Tumours arising from the inner
sphenoidal ridge cause compression of the adjacent optic nerve and patients
may present with a history of uniocular visual failure. If the tumour is large
enough to cause raised intracranial pressure papilloedema will develop in the
contralateral eye. syndrome is known as the Foster Kennedy. Inner sphenoidal
ridge tumours may also cause compression of the
olfactory tract, resulting in
anosmia. Patients with tumours involving the outer sphenoidal ridge present
with features of raised intracranial pressure, often severe papilloedema with
relatively inconspicuous localizing symptoms or signs. Tumours in this region
occur as a thin sheet, and are known as ‘en plaque’. They may cause an
excessive bony reaction (hyperostosis) resulting in proptosis.
Fig. 7.4 (a) CT scan. Hyperostosis of the
left sphenoidal ring causing unilateral proptosis due to a sphenoidal ring
meningioma. (b) MRI. Inner sphenoidal wing meningioma.
Olfactory groove tumours (Fig. 7.5)
Olfactory groove meningiomas cause
anosmia, initially unilateral and later bilateral. The presenting features may
include symptoms of raised intracranial pressure, and failing vision either
from chronic papilloedema or from direct compression of the optic nerve or
chiasm causing visual field defects. These tumours may also present with the
Foster Kennedy syndrome and the intellectual and psychiatric problems caused by
frontal lobe compression described for inner spheroidal ridge
meningiomas.
Suprasellar tumours
Suprasellar meningiomas arising from
the tuberculum sellae will cause visual failure and a bitemporal hemianopia,
but the lack of endocrine disturbance will distinguish the clinical
presentation of this tumour from that of a pituitary tumour.
Ventricular tumours
Tumours arising in the lateral
ventricle present with symptoms of raised intracranial pressure extending over
several years and associated with a mild global disturbance of function of one
hemisphere and frequently a homonymous hemianopia.
Posterior fossa tumours
Posterior fossa tumours may arise
from the cerebellar convexity or from the cerebellopontine angle or clivus. The
cerebellopontine angle tumours simulate an acoustic neuroma with symptoms
involving the acoustic nerve, trigeminal nerve and facial nerve, ataxia due to
cerebellar involvement and raised intracranial pressure, often due to
hydrocephalus caused by obstruction of the 4th ventricle. Meningiomas arising
from the clivus or the foramen magnum region may compress the brainstem
directly.
Radiological investigations
The CT scan appearance shows a
tumour of slightly increased density prior to contrast; it enhances vividly and
uniformly following intravenous contrast. Hyperostosis of the cranial vault may
be a focal process at the site of the tumour attachment or, as seen with en
plaque meningioma, a more diffuse sclerosis. These bone changes may also be
seen on plain skull X-ray.
Magnetic resonance imaging will
demonstrate meningiomas following the intravenous injection of gadolinium
contrast Meningiomas are usually isointense on T1- weighted images, but
enhance intensely and usually homogeneously following administration of
gadolinium.
Cerebral angiography is no longer
necessary as a diagnostic investigation but may be useful preoperatively to
ascertain the position of the cerebral vessels. It will demonstrate external
carotid artery supply to the tumour with a characteristic tumour blush,
differentiating it from a glioma or metastatic tumour (Fig. 7.12). Angiography
also allows preoperative embolization of the tumour, if necessary.
Preoperative management
Meningiomas are frequently
surrounded by severe cerebral oedema and patients should be treated with
high-dose steroids (dexamethasone) prior to surgery if possible. Preoperative
embolization of the tumour vasculature may be considered advisable in some
anterior basal and sphenoidal wing tumours where the major Vascular supply is not readily
accessible in the early stages of the operation.
Treatment
The treatment of meningiomas is
total surgical excision, including obliteration of the dural attachment.
Although this objective is usually possible there are some situations where
complete excision is not possible because of
the position of the tumour. Tumours arising from the clivus, in front of the
brainstem or those situated within the cavernous sinus, are notoriously
difficult to excise without causing serious morbidity. Radiation therapy may be
used to treat residual tumours following subtotal resection, in order to reduce
the risk of recurrent growth. Stereotactic radiotherapy has been used to treat
small meningiomas (less than
Postoperative management
The postoperative care of patients
following excision of a meningioma involves the routine management of patients
following a craniotomy but with particular attention to the minimization of
cerebral oedema. Steroid therapy is continued initially and gradually tapered.
Care is taken to avoid excessive hydration and the patient is nursed with the
head of the bed elevated to promote venous return. Neurological deterioration
requires urgent assessment and a CT scan will determine the pathological cause,
either postoperative haemorrhage or cerebral oedema.
Tumour recurrence
The risk of tumour recurrence
depends on the extent of tumour excision. When the tumour and its dural origins
are completely excised, the risk of recurrence is remote. The most common
source of recurrence is from a tumour that has invaded a venous sinus and which
was not resected (e.g. superior sagittal sinus or cavernous sinus). Recurrence
is more common if the tumour has histological features of malignancy.
Meningeal haemangiopericytoma
Meningeal haemangiopericytoma is a malignant neoplasm with sarcoma-like
behaviour. It was originally classified by Cushing and Eisenhardt in 1938 as an
angioblastic variant of meningioma.The tumour’s radiological and macroscopic
appearance resembles a vascular meningioma, but it arises from the meningeal
capillary pericyte and typically contains a subpopulation of cells that express
actor VIIIa. The tumour incidence is 2–4% of meningioma and it is
slightly more common in males than in females.
The presenting features are dependent on the tumour location, with symptoms
usually being present for less than 1 year.
Acoustic neuroma
Acoustic schwannomas arise from the
8th cranial nerve and account for 8% of intracranial tumours. Schwannomas occur
less frequently on the 5th cranial nerve and rarely involve other cranial
nerves. The acoustic schwannoma takes origin from the vestibular component of
the 8th cranial nerve near the internal auditory meatus, at the transition zone
where the Schwann cells replace the oligodendroglia. As such it should more
correctly be called a vestibular schwannoma, although the term acoustic neuroma
or schwannoma is more commonly used.
Macroscopically, the acoustic schwannoma is lobulated with a capsule that
separates it from the surrounding neural structures. Small tumours usually
arise from within the internal auditory canal and occupy the porus of the
internal auditory canal and, as the tumour grows, the 8th nerve is destroyed
and the adjacent cranial nerves become stretched around the tumour. The 7th
nerve is typically displaced on the ventral and anterior surface of the tumour
and the trigeminal nerve is carried upwards and forwards by the upper pole. The
6th nerve lies ventral and usually medial to the major mass and the lower
cranial nerves are displaced around the inferior pole of the tumour. As the
tumour grows medially it compresses and displaces the cerebellum and distorts
the brainstem. Large tumours will result in obstruction of the 4th ventricle
and hydrocephalus.
Bilateral acoustic neuromas are the
hallmark of neurofibromatosis type 2 (NF2), inherited as an autosomal dominant
condition Clinical presentation
The presenting features will depend
on the size of the tumour at the time of diagnosis. The earlier symptoms are
associated with 8th nerve involvement. Tinnitus and unilateral partial or
complete sensorineural hearing loss are the earliest features. Episodes of
vertigo may occur but these may be difficult to distinguish from
Menière’s disease. Although the tumour causes compressionof the facial
nerve, the growth of the tumour is so slow that facial paresis is not evident
until the tumour is large. At that stage 5th nerve compression may be evident,
with diminished facial sensation and a depressed corneal reflex. Cerebellar
involvement will result in ataxia, and compression of the pyramidal tracts from
a very large tumour causing brainstem compression will cause a contralateral
hemiparesis. If a large tumour has caused obstructive hydrocephalus the patient
will also present with features of raised intracranial pressure.
Radiological investigations
The CT scan or MRI will show an
enhancing tumour extending from the internal auditory canal into the
cerebellopontine angle (Fig. 7.13). The internal auditory meatus will be
widened indicating that the tumour has arisen from the 8th cranial nerve (Fig.
7.14). While there is no difficulty in diagnosing a tumour large enough to be
evident on the CT scan, very small acoustic neuromas, which are predominantly
within the internal auditory canal, may be more difficult to diagnose. These
tumours may be seen on highquality CT scan but are particularly evident using
MRI, especially following gadolinium contrast (Fig. 7.15), which is now the
investigation of choice.
Fig. 7.13 Acoustic neuroma.
Other investigations
Pure tone audiometry, by both air
and bone conduction, is an essential part of the investigation of a patient
with an acoustic neuroma, the most common finding being high-frequency hearing
loss. Other special auditory tests include the use of brainstem auditory evoked
responses which are particularly sensitive for changes in the retrocochlear
auditory system; these are helpful in diagnosing a small intracanalicular
tumour. Vestibular function is impaired early in patients with acoustic
neuroma. The Hallpike caloric test is carried out with the patient supine on a
couch and the head raised to
Differential diagnosis
The major differential diagnoses for a cerebello-pontine angle tumour, in
decreasing frequency, are: meningioma, metastatic tumour, exophytic brainstem glioma, epidermoid tumour.
Treatment
The total excision of a large
acoustic neuroma remains one of the major operative challenges in what Cushing
has described as ‘the gloomy corner of neurologic surgery’.
The aim of the operation is complete
resection of the tumour while sparing the adjacent neural structures. If the
patient presents with a large tumour causing severe hydrocephalus and raised
intracranial pressure, a preliminary ventriculoperitoneal shunt or ventricular
drain may be considered. Steroid administration prior to surgery may be
advisable if the tumour is large.
There are three basic approaches to
the cerebellopontine angle: by excision of the labyrinth (translabyrinthine);
through a posterior fossa craniectomy
(suboccipital/retrosigmoid); or via the middle cranial fossa. The route chosen
is governed by tumour size, the degree of hearing loss, the hearing level in
the contralateral ear, and the surgical preference and expertise of the
operator.
The major advantage of the translabyrinthine operation is that the facial
nerve can be identified lateral to the tumour at an early stage in the dissection,
and access to the fundus of the internal auditory meatus is excellent.
Furthermore, retraction of the cerebellum is minimal and the risk of
postoperative oedema is consequently less. The major disadvantage of this route
is that residual hearing is irrevocably destroyed. translabyrinthine operation
is favoured for large tumours, regardless of hearing level, and for
medium-sized lesions with poor hearing. It provides a more direct approach to
the cerebellopontine angle, and retraction of the cerebellum is negligible.
As a consequence of progressive improvements in operative results,
particularly in mortality and facial nerve outcome, attention has
turned more recently to the ability to preserve useful hearing. The
suboccipital operation provides good access to the cerebellopontine angle but,
if hearing is to be conserved, tumour at the fundus of the internal auditory
meatus may be difficult to expose under direct vision. For hearing preservation
the retrosigmoid approach for tumours with up to
Recently there has been renewed interest in the middle fossa approach for
removal of intracanalicular tumours or those with a small cerebellopontine
angle component, particularly where the tumour in the internal auditory canal
extends to the fundus. Higher rates of hearing preservation have been reported
without any compromise of facial nerve function, but this route provides more
limited access to the cerebellopontine angle, and is therefore restricted to
the treatment of small lesions. The middle fossa approach is preferred for
intracanalicular tumours and for those with up to
Stereotactic radiosurgery using
either a 60CO Gamma Knife or a highly focused linear accelerator has been
advocated for the treatment of smaller tumours, less than
There is continuing debate as to the relative advantages of surgery and
stereotactic radiation treatment. Whilst some clinicians advocate radiation
treatment for smaller tumours, others would only recommend it for elderly or
medically infirm patients or if there is residual tumour or regrowth after
subtotal resection.
The management plan for patients with bilateral acoustic neuromas (NF2) is
complex, and must be tailored for each patient, with the aim of preserving
useful hearing for as long as possible, whilst minimizing the possible serious
neurological complications from enlarging tumours causing cranial nerve,
cerebellar and brainstem compression. Therapeutic options include surgery,
radiosurgery and hearing preservations/restoration utilizing brainstem
electrode implants at the time of tumour resection.
Haemangioblastoma
Haemangioblastomas are uncommon intracranial tumours accounting for 1–2% of
all brain tumours and approximately 10% of posterior fossa tumours.
The haemangioblastoma arises from proliferation of endothelial cells. The
tumour usually occurs in young adults, although it may occur at any age. It
usually occurs in the posterior fossa and often produces a large cyst. Although
haemangioblastoma may occur as a component of von Hippel–Lindau’s disease,
which includes multiple haemangioblastomas, haemangioblastomas of the retina
(von Hippel tumour), renal tumour, renal cyst, pancreatic cyst and tubular
adenomata of the epididymis, the majority of patients with the cerebellar
tumour do not have von Hippel–Lindau’s disease. Incomplete forms of the
syndrome may occur and cerebellar haemangioblastomas occur in about 20% of
patients with retinal haemangioblastoma.
The tumour presents as a slowly growing posterior fossa mass with features
of raised intracranial pressure and cerebellar involvement. Occasionally the
patient may be polycythaemic due to increased circulating erythropoietin.
CT scan or MRI show a cerebellar tumour which may involve the vermis and
hemispheres and which shows vivid enhancement following intravenous contrast.
There is usually a low-density cyst surrounding the tumour nodule (Fig. 7.17),
although haemangioblastomas may sometimes be solid. If considered necessary,
vertebral angiography will confirm the highly vascular mass.
Total surgical excision through a posterior fossa craniotomy is nearly
always possible. Great care must be taken not to enter the highly vascular
tumour during the dissection and excision.
Colloid cyst of the 3rd ventricle
The colloid cyst of the 3rd ventricle is situated in the anterior part of
the ventricle and is attached to the roof just behind the foramen of Monro.
Several possibilities as to the origin of the tumour have been proposed,
including the paraphysis, choroid plexus epithelium, ependyma or a diverticulum
of the diencephalon.
The cyst consists of a thin, outer fibrous capsule lined by a layer of
epithelium; the contents consist of mucoid material, epithelial debris and
mucin. The cyst may be very small and asymptomatic. As the tumour grows it will
cause bilateral obstruction to the foramina of Monro, leading to raised
intracranial pressure from hydrocephalus. The headaches may fluctuate, being
aggravated by stooping and relieved by standing upright. Episodes of abrupt,
sudden leg weakness causing the patient to fall may occur without a change in
conscious state. Alternatively, an abrupt loss of consciousness may occur and
this, although usually transient, might be fatal.
The usual CT scan picture is a high-density, rounded tumour in the anterior
3rd ventricle which enhances following intravenous contrast (Fig. 7.18),
although isodense, hypodense and non-enhancing tumours have been reported. MRI
helps to define the position of these tumours (Fig. 7.18) and will be able to
differentiate between a colloid cyst and an aneurysm of the basilar tip, which
may occasionally be indistinguishable on CT scan.
Surgical excision is performed through a craniotomy with a small incision
in the anterior corpus callosum giving access to the lateral ventricle. The
tumour is seen expanding the foramen of Monro and, using the operating
microscope, a complete excision is usually possible. Great care must be taken
during the operation to preserve the venous structures, including the septal
veins, thalamostriate vein and internal cerebral veins. Damage to the columns
of the fornix will result in severe
postoperativememory disturbance.
Epidermoid and dermoid cysts
Epidermoid and dermoid cysts arise from epithelial cells embryologically
misplaced intracranially, particularly into the meninges and ventricles and,
less frequently, into the parenchyma of the brain. Rarely, the cells can be
implanted as a result of trauma such as a lumbar puncture, which can implant
skin into the spinal canal causing an epidermoid cyst.
Epidermoid tumours are found principally in the arachnoid spaces, the
cisterns or the diploe of the bone. The most frequent localizations are the
cerebellopontine angle, the suprasellar and parasellar regions, the lateral or
4th ventricles, and the quadrigeminal cistern. Dermoid tumours occur mostly in
the posterior fossa as a midline lesion and a fistula may connect the dermoid
with the skin.
The epidermoid cyst contains desquamated epithelium surrounded by
keratin-producing squamous epithelium. The dermoid cyst includes dermal
elements such as hair follicles, sebaceous glands and sometimes sweat glands.
The cysts usually present following a long history of symptoms related to
their position. Cranial nerve abnormalities such as trigeminal neuralgia and
hemifacial spasm may occur with cerebellopontine angle epidermoid tumours and
the suprasellar cyst will produce visual impairment with optic atrophy and
often a bitemporal hemianopia. Leakage of epidermoid cyst contents may result
in a chemical meningitis, and in patients with posterior fossa dermoid cysts,
bacterial meningitis may occur through the dermal sinus connecting the cyst
with the skin.
The CT scan of an epidermoid cyst is characterized by a low-density lesion
that does not enhance. The dermoid cyst will also have areas which are even less
dense than CSF, indicating the presence of fat (Fig. 7.19). MRI has superceded
CT for accurate preoperative evaluation and planning. Epidermoid lesions are
usually manifest as low signal on T1 and high signal on T2 images, although
depending on lipid content, variable signal intensities may be seen within
thesame lesion.
The treatment is operative, with resection of the cyst. Complete excision
may be prevented if the cyst wall is densely adherent to major vessels and
important neural structures.
PITUITARY ADENOMAS
Pituitary adenomas account for 8–10%
of all intracranial tumours.
In 1886 Pierre Marie first made the
connection between acromegaly and pituitary adenomas. Patients may present
either with signs of endocrine disturbance or with compression of the adjacent
neural structures, especially the optic pathways.
Classification
Historically, three main types of
pituitary adenomas were defined by their cytoplasmic staining characteristics:
chromophobic, acidophilic and basophilic—the implication being that these
tumours were either hormonally inactive, secreted growth hormone, or produced
adrenocorticotrophic hormone (ACTH), respectively.
The development of immunoperoxidase
techniques and electron microscopy has provided a more refined classification
of pituitary adenomas based on the specific hormone that is produced. This
classification is shown in Table 8.1.
Pathology
Pituitary adenomas arise from the
anterior lobe (adenohypophysis) of the pituitary gland which develops from
Rathke’s pouch, an ectodermal diverticulum arising from the roof of the
stomodeum, immediately in front of the buccopharyngeal membrane. The posterior
lobe (neurohypophysis/pars nervosa) arises from the infundibulum developing
from the floor of the diencephalon (Fig. 8.1).
The tumour arises within the
pituitary fossa. If it is less than
pathways, particularly the optic
chiasm. Further growth superiorly causes compression of the hypothalamus and,
if large enough, obstruction of the 3rd ventricle, resulting in hydrocephalus
(Figs 8.2).
The tumour may also grow laterally
out of the sella into the cavernous sinus. Occasionally the lateral extension
may be sufficient to cause disturbance of the cranial nerves in the cavernous sinus.
Uncommonly the tumour penetrates further laterally, into the temporal lobe.
The tumour may infrequently extend
inferiorly through the floor of the pituitary fossa into the sphenoid sinus,
resulting in CSF rhinorrhoea.
The localization of microadenomas within the pituitary fossa corresponds
somewhat with the regional distribution of the normal adenohypophyseal cells.
Prolactin- and growth hormonesecreting microadenomas tend to occur laterally,
whereas most adenomas secreting ACTH occur in the central zone.
Multiple endocrine neoplasia type 1 (Werner’s syndrome) is an autosomal
dominant disorder representing the inherited occurrence of both benign and
malignant neoplasms involving the pituitary gland, parathyroid gland and
pancreas.
About 10% of pituitary adenomas are invasive, with extensive penetration of
the pituitary capsule, dural sinuses and surrounding bone. Most invasive
pituitary adenomas are sparsely granulated or chromophobic and are either
hormonally inactive or prolactin producing. Metastasizing pituitary carcinoma,
either extracranially or throughout the CSF pathway, is extremely rare.
Clinical presentation are due to:
• the size of the tumour
• endocrine disturbance.
Headache occurs principally in
patients with macromegaly and is uncommon in other
types of pituitary tumour.
Visual failure
Careful assessment of the visual
fields, the visual acuity and the optic fundi is essential. Suprasellar
extension of the pituitary tumour causes compression of the optic chiasm
resulting in a bitemporal hemianopia. The bitemporal hemianopia initially
involves the upper quadrants,before extending to the lower quadrants of the visual field. If the chiasm is
prefixed, that is, placed more anteriorly than usual, a homonymous hemianopia
may occur due to compression of the optic tract. Bilateral central scotomas
result from the tumour pressing on the posterior part of the chiasm where the
macular fibres decussate. Primary optic atrophy will be evident in patients
with long-standing compression of the chiasm. Ocular palsies occur in about 10%
of patients and are due to invasion of the cavernous sinus. The 3rd nerve is
the most frequently affected, followed by the 6th and 4th cranial nerves.
Facial pain results from compression of the trigeminal nerve, usually the
ophthalmic division, as a result of cavernous sinus invasion.
Endocrine abnormalities
Endocrine disturbance is due to
either hypopituitarism or excess secretion of a particular pituitary hormone.
Hypopituitarism
Hypopituitarism results from failure
of the hormones secreted by the adenohypophysis and it gives rise to the
clinical features first described by Simmonds in 1914. Pituitary gland failure
does not occur if the tumour is a microadenoma, but may be clinically evident
in the larger tumours. The endocrine secretions are not equally depressed but
there is a selective failure and the order of susceptibility is as follows:
growth hormone, gonadotrophin, corticotrophin, thyroidstimulating hormone.
Gonadotrophic deficiency prior to
puberty retards the development of secondary sex characteristics; adult men
have poor beard growth, women suffer from amenorrhoea and both sexes have loss
of libido and deficient pubic and axillary hair. The biochemical abnormality is
manifest by a low oestrogen and androgen production with reduced urinary
17-ketosteroids. Hypopituitarism initially results in vague symptoms, including
lack of energy, undue fatiguability, muscle weakness and anorexia and, when
prolonged and severe, it will cause low blood pressure. Clinical hypothyroidism
is manifest by physical and mental sluggishness and a preference for warmth.
When the hypopituitarism is severe, episodic confusion occurs and the patient
will become drowsy. It is essential to recognize the features of severe
pituitary insufficiency as an endocrine crisis can be precipitated by minor
stressful events occurring during hospital investigation or as a result of an
intercurrent infection.
Pituitary apoplexy results from
spontaneous haemorrhage into a pituitary tumour. It is characterized by sudden,
severe headache followed by transient or more prolonged loss of consciousness
with features of neck stiffness, vomiting and photophobia. The condition is
similar to subarachnoid haemorrhage resulting from a ruptured aneurysm, but is
often associated with paralysis of one or more of the ocular muscles (usually
bilateral) and acute visual deterioration. An acute endocrine crisis may be
precipitated by
the apoplexy.
Prolactinoma
The prolactin-secreting tumour may
be a microadenoma or macroadenoma within the pituitary fossa. The patients are
usually women who present with infertility associated with amenorrhoea and
galactorrhoea, although the tumour may occasionally cause infertility in men.
Large prolactinomas occur in the elderly and in males, and these can cause
endocrine disturbance associated with hypopituitarism and visual failure.
Acromegaly
Acromegaly results from a growth
hormonesecreting pituitary adenoma which, as described previously, consists of
cells that stain either as acidophils, chromophobes or both. The onset of
acromegaly is slow and insidious, usually during the 3rd and 4th decades of
life, with both sexes being affected equally. The clinical features (Table 8.3)
include bone and soft tissue changes that are evident as an enlarged
supraciliary ridge, enlarged frontal sinuses and increased mandibular size,
which will cause the chin to project (prognathism) (Fig. 8.6). The hands and
feet enlarge, and the skin becomes coarse and greasy and sweats profusely. The
voice becomes hoarse and gruff and thoracic kyphosis occurs as a result of
osteoporosis. Other problems associated with acromegaly include hypertension,
cardiac hypertrophy and diabetes. Headache is often severe in patients with
pituitary tumours causing acromegaly and patients complain of lack of energy,
physical weakness and lassitude. Suprasellar extension of the tumour occurs in
about 15% of cases and may result in compression of the optic pathways.
A pituitary adenoma with excessive
growth hormone secretion occasionally presents in childhood and results in
gigantism.
Cushing’s disease
Cushing’s disease is due to
ACTH-producing pituitary adenomas. Over 80% of the tumours are microadenomas
and the remainder are macroadenomas involving the whole of the sella or with
extrasellar extension. The onset is insidious and the disease may affect
children or adults. Severe obesity occurs, the skin is tense and painful, and
purple striae appear around the trunk. Fat is deposited, particularly on the
face (moon face), neck, cervicodorsal junction (buffalo hump) and trunk. The
skin becomes a purple colour due to vasodilatation and stasis. Spontaneous
bruising is common. The skin is greasy, acne is common and facial hair
excessive. Patients complain of excessive fatigue and weakness. There is wasting
and flaccidity of the muscles. Osteoporosis predisposes to spontaneous
fractures.
Glucose tolerance is impaired, the
serum potassium is low and vascular hypertension occurs. If untreated, 50% of
cases are fatal in 5 years.
Laboratory investigations
Radioimmunoassay will help to identify the hormone being secreted.
Serum prolactin level in patients with prolactinomas will vary from just
above the upper limit of normal to values greater than 20 000 mIU/l (normal
70–550 mIU/l). The levels may show considerable variation in a particular
patient and prolactin levels greater than 2000 mIU/l are almost always
indicative of a pituitary tumour. As mentioned previously, hyperprolactinaemia
may be associated with other pituitary tumours and has been noted in some
patients with acromegaly. Null cell tumours may be associated with mild
hyperprolactinaemia due to distortion of the pituitary stalk or impingement on
the hypothalamus.
Serum growth hormone is measured by radioimmunoassay, the normal values
being less than 5 mIU/l in males and less than 10 mIU/l in females. Growth
hormone exerts its effects on peripheraltissues indirectly via
somatomedins—polypeptides produced primarily by the liver and fibroblasts.
Serum somatomedin C (insulinlike growth factor I, IGF-I) is a more accurate
indicator of growth hormone bioactivity than the serum growth hormone levels.
Provocative tests of growth hormone secretion are useful in confirming
acromegaly. Most patients with acromegaly
do not show the normal suppression of growth hormone following glucose load.
Other provocative tests utilize thyrotrophinreleasing hormone and growth
hormonereleasing hormone.
In contrast to other pituitary tumours that rely on imaging studies as the
foremost diagnostic investigation, a careful endocrinological assessment is
critical in the diagnosis of Cushing’s disease, especially as in nearly 50% a
tumour is not evident on MRI.
There are three essential steps in the diagnosis of Cushing’s disease due
to pituitary pathology.
1 Confirm
excess secretion of cortisol (normal 120–650 nmol/l).
2 Distinguish
ACTH-dependent from ACTH-independent causes of hypercortisolaemia.
3 Distinguish
pituitary-based Cushing’s disease from ectopic states of ACTH production.
A24-hour urine specimen is the simplest initial means of establishing
hypercortisolaemia.
The investigation of Cushing’s disease involves the measurement of ACTH by
radioimmunoassay of samples of both peripheral blood and blood from the
petrosal sinus. A differential level of ACTH in petrosal vein blood and
peripheral blood will help confirm the presence of a pituitary basis for the
ACTH production, especially after administration of corticotrophin-releasing
hormone (CRH). A dexamethasone suppression test will help diagnose Cushing’s
syndrome and its cause. The urine- and plasma-free cortisol is measured and is
normally suppressed following administration of low-dose dexamethasone (0.5 mg
6-hourly). The levels will be suppressed following high-dose dexamethasone (2mg
6-hourly) in pituitary-dependent Cushing’s disease. There will be a failure of
suppression of the levels with high-dose dexamethasone if the Cushing’s
syndrome is due to other than pituitary causes.
Radiological investigations
High-resolution CT scanning and
magnetic resonance imaging using thin slices and intravenous contrast are the
appropriate investigation. Pituitary microadenomas are usually hypodense and
may cause upward bulging and convexity of the upper border of the gland in
adults, deviation of the pituitary stalk and thinning of the sellar floor on
the side of the tumour.
High-quality CT scanning is able to demonstrate tumours as small as
MRI has improved the identification
of microadenomas, which appear as low-density focal lesions on T1-weighted
scans and high intensity on T2-weighted scans (Fig. 8.9). Macroadenomas usually
appear as isointense on the T1-weighted images and moderately hyperintense on
the T2- images. Haemorrhage into a tumour, such as occurs following pituitary
apoplexy, shows as high-intensity areas because of methaemoglobin on the T1-
and T2-weighted scans intermingled with low-density regions due to haemosiderin
(see Figs 8.5 and 8.9). Dynamic scans taken at 30-second intervals following
intravenous gadolinium may help demonstrate small microadenomas.
Plain skull X-rays may show
enlargement of the sella with thinning erosion or bulging of its contours (Fig.
8.11).
In the past angiography has been
performed to exclude incidental aneurysms and to determine the position of the
internal carotid arteries in the cavernous sinuses, but this information can
now be obtained satisfactorily from good-quality MRI and, if necessary, magnetic
resonance angiography.
Differential diagnosis
The major differential diagnoses
are:
• craniopharyngioma
• suprasellar meningioma (arising
from the tuberculum sellae).
Uncommon masses around the
suprasellar region also include optic nerve and hypothalamic glioma, giant
aneurysm arising from the carotid artery, Rathke’s cleft cysts, suprasellar
germinomas and chordomas.
Treatment
The objectives of treatment of
patients with pituitary tumours depend on whether the patient has presented
with features of endocrine disturbance or problems related to compression of
adjacent neural structures. The methods of treatment used are:
1 Operative procedures:
(a) transsphenoidal excision
(b) transcranial excision.
2 Radiotherapy.
3 Medical treatment with antisecretory
drugs.
Surgical excision
This will be used as the primary
method of treatment for:
• large tumours causing compression
of adjacent adjacent neural structures, particularly the visual pathways
• GH-secreting tumours causing
acromegaly
• ACTH-secreting tumours causing
Cushing’s disease
• the occasional treatment of a
prolactin-secreting adenoma, either microadenoma or macroadenoma confined
within the sella, when medical treatment using bromocriptine is not tolerated.
Most tumours can be excised via the
transsphenoidal approach to the pituitary fossa
The development of the surgical microscope and fluoroscopic radiography has
made this a safe procedure. The sphenoid sinus is usually entered using a
unilateral trans-septal approach, with the incision either in the nasal mucosa
or sublabially. The mucosa is reflected from the nasal septum and floor and the
sphenoid is opened. The anterior wall of the sella is removed and the pituitary
fossa entered. Microadenomas (tumours less than 10mm in diameter) may be
evident on the surface of the gland or may become evident only once the gland
is incised. These tumours can be completely excised, preserving pituitary
function. The suprasellar extension of the tumour can be gently coaxed down
into the pituitary fossa by slightly raising the intracranial pressure using a
Valsalva manoeuvre or by the anaesthetist injecting small increments of nitrous
oxide and oxygen mixture into the lumbar theca until the intracranial pressure
forces the suprasellar tumour into the operative field. This will also have the
additional benefit that the intracranial gas will provide a
pneumoencephalogram, outlining the remaining suprasellar extension of tumour.
A transcranial operation is
occasionally necessary, particularly where there is a subfrontal or retroclival
extension of the tumour.
Postoperative management requires
careful attention to the fluid balance and hormonal status. Endocrine
deficiency in the immediate postoperative period will require replacement with
parenteral hydrocortisone and possibly the use of vasopressin for the treatment
of diabetes insipidus, which often
occurs at least transiently after the excision of a large pituitary tumour. In
the early postoperative period aqueous vaso-pressin (Pitressin ®) should be
given by intramuscular or subcutaneous injection and, if the diabetes insipidus
persists, by the intranasal route. Other long-term hormonal replacements may
include cortisone acetate (12.5–25 mg twice daily), thyroxine and testosterone.
Radiotherapy
Postoperative radiotherapy may be
used if there has been a subtotal excision of the tumour or if the
postoperative endocrine studies demonstrate residual excessive hormone
secretion.
Medical treatment
Treatment of pituitary adenomas is
undertaken to restore the endocrine status of the patient by replacement of
either the pituitary hormone itself or the hormone of the pituitary-dependent
glands. This will be a necessary preoperative procedure in patients with
evidence of hypopituitarism and
will frequently be necessary after the surgical excision of a macroadenoma.
Prolactin-secreting pituitary tumours are treated with bromocriptine, a
dopamine agonist. This is the preferred treatment for a symptomatic prolactin-
secreting microadenoma and may be used either as the definitive treatment of
larger prolactin- secreting tumours or in conjunction with surgery. Some
patients show poor tolerance to bromocriptine, as it may cause intractable
nausea, vomiting and postural hypotension, and these patients will require
surgical treatment of the tumour.
Craniopharyngioma
This tumour may occur at any age,
although nearly half occur in the first 20 years of life. They are thought to
arise from the epithelial remnants of Rathke’s pouch. The tumours occur in the
region of the pituitary fossa and extend through the suprasellar cisterns to
the hypothalamus. There are two histological types of tumours. The adamantinous
type resembles adamantinoma of the jaw and is encountered in virtually all
children. The papillary type, so-called adult craniopharyngioma, occurs in
about one-third of adults and is rare in children.
Clinical presentation
Clinical features include:
• raised intracranial pressure
• visual impairment
• endocrine dysfunction.
Raised intracranial pressure
This is common, particularly in
children, who present with headache, vomiting and papilloedema.
Visual impairment
This is due to papilloedema,
chiasmal compression or a combination of both. Papilloedema is due to
hydrocephalus as a result of 3rd ventricular obstruction by the tumour. The
visual field defect is frequently similar to that produced by a pituitary
tumour, a bitemporal hemianopia, but homonymous defects are more common than in
pituitary adenoma.
Endocrine abnormalities
These are frequent in children and
consist of:
• hypogonadism
• stunting of growth
• diabetes insipidus.
Endocrine failure due to
craniopharyngioma arising in adults is essentially similar to that caused by a
pituitary tumour, except that diabetes insipidus occurs more commonly in
patients presenting with craniopharyngioma.
Investigations
The CT scan usually shows a cystic
tumour in the suprasellar region with calcification (Fig. 8.14). Tumours in
adults may be solid and are less calcified than those seen in younger patients.
MRI is useful in showing the full extent of the tumour (Fig. 8.15). Changes in
the sella turcica are seen in approximately 50% of patients. Suprasellar
tumours and the associated hydrocephalus press downwards on the dorsum sellae
and anterior clinoids and may enlarge the sella. Nearly 90% of tumours in
children have radiographically identifiable calcification in the tumour,
whereas only 40% of adults have radiologically demonstrable calcification. The
calcification consists of aggregates of small flecks of calcium and may be
curvilinear, outlining a portion of the cyst wall.
Treatment
Preoperative visual and endocrine
assessment is essential. The standard treatment for craniopharyngioma is
operative, with an attempt at maximal resection of the tumour. However,
complete resection may not be possible due to the extent of the tumour and the
intimate attachment to hypothalamic vital structures. The usual surgical
approach is through a pterional craniotomy or a bifrontal craniotomy with
separation of the frontal lobes and division of the lamina terminalis. Tumours
extending into the 3rd ventricle may also need to be approached through the
corpus callosum. An extended transsphenoidal approach is sometimes advised for
those tumours extending down to the floor of the pituitary fossa.
Postoperative management will
include careful attention to fluid and electrolyte balance as many patients
have at least a transient diabetes insipidus following surgery. Other hormones
may need replacement depending on endocrinological assessment.
The role of postoperative
radiotherapy in patients with a subtotal resection is controversial but
radiotherapy may be beneficial in decreasing the production of cyst fluid and
delaying recurrence of the tumour.
Empty sella syndrome
The empty sella refers to a communicating extension of the subarachnoid
space into the pituitary fossa. This may occur as a result of an incomplete
anatomical formation of the diaphragma sellae which allows the arachnoid to
herniate directly into the pituitary fossa or as a secondary phenomenon
following either pituitary There is good reason to regard the empty sella as an
anatomical variant rather than a syndrome. However, defects in the diaphragma
are not the only requirement for formation of an empty sella. Increased intracranial
pressure associated with benign intracranial hypertension or long-standing
hydrocephalus will cause herniation of the subarachnoid space into the sella
and will result in the remodelling of the pituitary fossa to produce the
classic globular appearance on plain X-ray and CT scan (Fig. 8.18). It is
possible that the normal variations in CSF pressure may be transmitted into the
fossa through an incompetent diaphragma and so result in the bony changes.
Clinical presentation
Most patients with the radiological features of an empty sella are
asymptomatic. The majority of patients presenting with symptoms are obese,
middle-aged, hypertensive women. Headache is the most common symptom associated
with the empty sella but the features are so varied that their relevance to the
intrasellar subarachnoid space is dubious without an underlying cause for
possible raised intracranial pressure. Visual field defects and endocrine
abnormalities are subtle and uncommon in patients with primary empty sella
syndrome. In patients with a secondary empty sella, e.g. following surgery or
radiotherapy, field defects may be more pronounced but are rarely severe.
The most serious consequence of an empty sella is spontaneous CSF
rhinorrhoea. This usually occurs only if there has been an underlying cause of
raised intracranial pressure, such as benign intracranial hypertension. It is
managed by repairing the leak in the floor of the sella with crushed muscle and
fascia lata and performing a CSF shunt.