It is unlikely that high intracranial pressure alone directly damages neuronal tissue, but brain damage occurs as a result of tonsillar or tentorial herniation (see page 81). A progressive increase in intracranial pressure due to a supratentorial haematoma initially produces midline shift. Herniation of the medial temporal lobe through the tentorial hiatus follows (lateral tentorial herniation), causing midbrain compression and damage. Uncontrolled lateral tentorial herniation or diffuse bilateral hemispheric swelling will result in central tentorial herniation. Herniation of the cerebellar tonsils through the foramen magnum (tonsillar herniation) and consequent lower brain stem compression may follow central tentorial herniation or may result from the infrequently occurring traumatic posterior fossa haematoma.

Infection

The presence of a dural tear provides a potential route for infection. This seldom occurs within 48 hours of injury. Meningitis may develop after several months or years.

DIFFUSE DAMAGE

Diffuse axonal injury

Shearing forces cause immediate mechanical damage to axons. Over the subsequent 48 hours, further damage results from release of excitotoxic neurotransmitters which cause Ca²⁺ influx into cells and triggers the phospholipid cascade (page 246). Genetic susceptibility conferred by the presence of the APOE ͛4 gene may also play a part. Depending on the severity of the injury, effects may range from mild coma to death.

The macrosopic appearance may appear entirely normal but in some patients pathological sections reveal small haemorrhagic tears, particularly in the corpus callosum or in the superior cerebellar peduncle.

Microscopic evidence of neuronal damage depends on the duration of survival and on the severity of the injury. After a few days, retraction balls and microglial clusters are seen in the white matter.

If the patient survives 5 weeks or more after injury then appropriate staining demonstrates Wallerian degeneration of the long tracts and white matter of the cerebral hemispheres. Even a minor injury causing a transient loss of consciousness produces some neuronal damage. Since neuronal regeneration is limited, the effects of repeated minor injury are cumulative.

Cerebral swelling

This may occur with or without focal damage. It results from either vascular engorgement or an increase in extra- or intracellular fluid. The exact causative mechanism remains unknown

Cerebral ischaemia

Cerebral ischaemia commonly occurs after severe head injury and is caused by either hypoxia or impaired cerebral perfusion. In the normal subject, a fall in blood pressure does not produce a drop in cerebral perfusion since ‘auto-regulation’ results in cerebral vasodilatation. After head injury, however, autoregulation is often defective and hypotension may have more drastic effects. Glutamate excess and free radical accumulation may also contribute to neuronal damage (see page 246).

MULTIPLE INJURY – PRIORITIES OF ASSESSMENT

Patients admitted in coma with multiple injuries require urgent care and the clinician must be aware of the priorities of assessment and management.

When intracranial haematoma is suspected, a CT scan is essential, especially before clinical signs are masked by a general anaesthetic required for the management of limb or abdominal injuries. However, if difficulty occurs in maintaining blood pressure, then urgent laparotomy or thoracotomy would take precedence over investigation of a possible intracranial haematoma.

HEAD INJURY – ASSESSMENT

Some patients may describe the events leading to and following head injury, but often the doctor depends on descriptions from witnesses.

Points to determine:

Period of loss of consciousness: relates to severity of diffuse brain damage and may range from a few seconds to several weeks.

Period of post-traumatic amnesia: the period of permanent amnesia occurring after head injury. This reflects the severity of damage and in severe injuries may last several weeks.

Period of retrograde amnesia: amnesia for events before the injury.

Cause and circumstances of the injury: the patient may collapse, or crash his vehicle as a result of some preceding intracranial event, e.g. subarachnoid haemorrhage or epileptic seizure. The more “violent” the injury, the greater the risk of associated extracranial injuries.

Presence of headache and vomiting: these are common symptoms after head injury. If they persist, the possibility of intracranial haematoma must be considered.

HEAD INJURY – CLINICAL ASSESSMENT

PETROUS FRACTURE

Bleeding from the external auditory meatus or CSF otorrhoea:

3. Conscious level – Glasgow Coma Score (GCS)

Assess patient’s conscious level in terms of eye opening, verbal and motor response on admission (see page 5) and record at regular intervals thereafter. An observation chart incorporating these features is essential and clearly shows the trend in the patient’s condition. Deterioration in conscious level indicates the need for immediate investigation and action where appropriate.

Note: This chart shows a ‘14 point scale’ with a maximum score of ‘14’ in a fully conscious patient. Many centres use a 15 point coma scale where ‘Flexion to pain’ is divided into ‘normal’ or ‘spastic’ flexion (see page 29).

4. Pupil response

The light reflex (page 142) tests optic (II) and oculomotor (III) nerve function. Although II nerve damage is important to record and may result in permanent visual impairment, it is the III nerve function which is the most useful indicator of an expanding intracranial lesion. Herniation of the medial temporal lobe through the tentorial hiatus may damage the III nerve directly or cause midbrain ischaemia, resulting in pupil dilatation with impaired or absent reaction to light. The pupil dilates on the side of the expanding lesion and is an important localising sign. With a further increase in intracranial pressure, bilateral pupillary dilatation may occur.

5. Limb weakness

Determine limb weakness by comparing the response in each limb to painful stimuli (page 30). Hemiparesis or hemiplegia usually occurs in the limbs contralateral to the side of the lesion. Indentation of the contralateral cerebral peduncle by the edge of the tentorium cerebelli (Kernohan’s notch) may produce an ipsilateral deficit, a false localising sign more often seen with chronic subdural haematomas. Limb deficits are therefore of limited value in lesion localisation.

6. Eye movements

Evaluation of eye movements does not help in immediate management, but provides a useful prognostic guide.

Eye movements may occur spontaneously, or can be elicited reflexly (page 30) by head rotation (oculocephalic reflex) or by caloric stimulation (oculovestibular reflex).

Abnormal eye movements may result from: brain stem dysfunction, damage to the nerves supplying the extraocular muscles or damage to the vestibular apparatus. Absent eye movements relate to low levels of responsiveness and indicate a gloomy prognosis.

Vital signs

At the beginning of the century, the eminent neurosurgeon Harvey Cushing noted that a rise in intracranial pressure led to a rise in blood pressure and a fall in pulse rate and produced abnormal respiratory patterns. In the past, much emphasis has been placed on close observation of these vital signs in patients with head injury, but these changes may not occur and when present are usually preceded by deterioration in conscious level. Close observation of consciousness is therefore more relevant.

Cranial nerve lesions

Basal skull fracture or extracranial injury can result in damage to the cranial nerves. Evidence of this damage must be recorded but, with the exception of a III nerve lesion, does not usually help immediate management. Full cranial nerve examination is difficult in the comatose patient and this can await patient co-operation.

Clinical assessment cannot reliably distinguish the type or even the site of intracranial haematoma, but is invaluable in indicating the need for further investigation and in providing a baseline against which any change can be compared.

HEAD INJURY – INVESTIGATION AND REFERRAL CRITERIA

IN THE ACCIDENT AND EMERGENCY DEPARTMENT (A&E)

Various guidelines now exist. The following are based on those from the National Institute for Health and Clinical Excellence (NICE). (Further details available at http://www.nice.org.uk).

Admit to Hospital	Discharge from A&E
• New abnormalities on imaging • Glasgow coma score < 15 (even if imaging normal) • Persistent vomiting or severe headache • Fits criteria for a CT scan within 8 hours • Other concerns, e.g. drugs, alcohol intoxication, other injuries, shock, meningism, CSF leak, suspected non-accidental injury

• If Glasgow coma score = 15

AND

• Appropriate supervision at home

• CT not indicated or

• Normal imaging head and spine

• All symptoms and signs resolved

Referral to Neurosurgical Unit

Transfer to the neurosurgical unit

Prior to the transfer, ensure that resuscitation is complete, and that more immediate problems have been dealt with (see page 221). Insert an oropharyngeal airway. Intubate and ventilate if the patient is in coma or if the blood gases are inadequate (PO₂ <8 kPa on air, 13 kPa on O₂ or CO₂ > 6 kPa). If the patient’s conscious level is deteriorating, an intravenous bolus infusion of 100 ml of 20% mannitol should ‘buy time’ by temporarily reducing the intracranial pressure.

NOTE: for comatose patients with an unstable systemic state from multiple injuries, a negative CT scan in the local hospital may avoid a dangerous transfer to the neurosurgical unit.

Cervical spine injury may accompany head injury. Guidelines also exist with criteria for investigation. (For full details see http://www.nice.org.uk/guidance/index.jsp?action=download&o=36259).

For ADULTS and CHILDREN 10 years and over

AP, Lateral and Odontoid Peg X-rays if	CT cervical spine if
• Impaired neck rotation to right or left • No indication for CT scanning • Not safe to assess clinically • Neck pain/midline tenderness + ≥ 65 years or dangerous mechanism of injury • To exclude injury urgently e.g. prior to surgery

• Patient intubated

• Continued suspicion despite X-rays

• Inadequate X-rays

• Undergoing CT scanning for another reason e.g. Glasgow coma score < 13 or multi-region trauma

HEAD INJURY – INVESTIGATION

CT scan: the investigation of choice for head injury (and cervical spine injury incertain circumstances – see page 227).

Scans must extend from the posterior fossa to the vertex, otherwise haematomas in these sites will be missed.

With diffuse axonal shearing injuries, small haematomas may be seen on CT scan scattered throughout the white matter, particularly in the corpus callosum, the subcortical white matter and in the brain stem adjacent to the cerebellar peduncles.

If hydrocephalus is present on the upper scan cuts, look carefully for a haematoma (extradural, subdural or intracerebral) in the posterior fossa, compressing and obstructing the 4th ventricle.

Further investigation may be required to exclude other coincidental or contributory causes of the head injury, e.g. drugs, alcohol, postictal state, encephalitis (Cause of coma, see page 86).

If a CT scan is not available, a skull fracture on X-ray identifies those at high risk of intracranial haematoma. In those patients, referral to a neurosurgical unit for a CT scan is essential (see page 227).

HEAD INJURY – MANAGEMENT

Management aims at preventing the development of secondary brain damage from intracranial haematoma, ischaemia, raised intracranial pressure with tentorial or tonsillar herniation and infection.

– Ensure the airway is patent and that blood oxygenation is adequate. Intubation is advisable in patients ‘flexing to pain’ or worse. Ventilation may be required if respiratory movements are depressed or lung function is impaired, e.g. ‘flail’ segment, aspiration pneumonia, pulmonary contusion or fat emboli. Hypoxia can cause direct cerebral damage, but in addition causes vasodilatation resulting in an increase in cerebral blood volume with subsequent rise in ICP.

– A space-occupying haematoma requires urgent evacuation (see over). If the patient’s conscious level is deteriorating, give an initial or repeat i.v. bolus of mannitol (100 ml of 20%). Coagulation should be checked and any deficits corrected.

– Scalp lacerations require cleaning, inspection to exclude an underlying depressed fracture and suturing.

– Correct hypovolaemia following blood loss – but avoid fluid overload as this may aggravate cerebral oedema. In adults, 2 litres/day of fluid is sufficient. Commence nasogastric fluids or oral fluids when feasible.

– Anticonvulsants (e.g. phenytoin) must be given intravenously if seizures occur; further seizures and in particular status epilepticus significantly increase the risk of cerebral anoxia.

– Monitor intracranial pressure (ICP), blood pressure and cerebral perfusion pressure (CPP) in selected patients with diffuse swelling or after evacuation of an intracranial haematoma. Maintain CPP either by raising blood pressure if low or by treating raised intracranial pressure.

– Brain protective agents include corticosteroids, free radical scavengers, calcium channel blockers, and glutamate antagonists. The evolution of axonal damage after a diffuse shearing injury provides a potential window of opportunity for treatment. Despite experimental animal studies revealing encouraging results, trials of these agents in head-injured patients have failed to show efficacy, perhaps due to insufficient patient numbers or a failure to target treatment at appropriate patients. A recent study of corticosteroids involving 10 000 patients has shown a worse outcome in the treatment group (the CRASH study).

– Operative repair of a dural defect is required if CSF leak persists for more than 7 days. (Many still use prophylactic antibiotics in patients with a CSF leak, but there is no conclusive evidence of their efficacy and they may do more harm than good by encouraging the growth of resistant organisms.) The development of meningitis requires prompt treatment with an empirical antibiotic.

INTRACRANIAL HAEMATOMA

Most intracranial haematomas require urgent evacuation – evident from the patient’s clinical state combined with the CT scan appearance of a space-occupying mass.

Extradural haematoma

Using the CT scan the position of the extradural haematoma is accurately delineated and a ‘horse shoe’ craniotomy flap is turned over this area, allowing complete evacuation of the haematoma. For low temporal extradural haematomas, a ‘question mark’ flap may be more suitable. If patient deterioration is rapid, a burr hole and craniectomy positioned centrally over the haematoma may provide temporary relief, but this seldom provides adequate decompression.

Subdural/intracerebral haematoma (‘burst lobe’)

Subdural and intracerebral haematomas usually arise from lacerations on the under-surface of the frontal and/or temporal lobes. Again the CT scan is useful in demonstrating the exact site. A ‘question mark’ flap permits good access to both frontal and temporal ‘burst’ lobes. The subdural collection is evacuated and any underlying intracerebral haematoma is removed along with necrotic brain.

N.B. Burr holes are insufficient to evacuate an acute subdural haematoma or to deal with any underlying cortical damage.

Conservative management of traumatic intracranial haematomas

Not all patients with traumatic intracranial haematomas deteriorate. In some, the haematomas are small and clearly do not require evacuation. In others, however, the decision to operate proves difficult, e.g. the CT scan may reveal a moderate-sized haematoma with minimal or no mass effect in a conscious but confused patient.

If conservative management is adopted, careful observation in a neurosurgical unit is essential. Any deterioration indicates the need for immediate operation. In this group of patients, intracranial pressure monitoring may serve as a useful guide. An intracranial pressure of 25 mmHg or more suggests that haematoma evacuation is required as the likelihood of subsequent deterioration with continued conservative management would be high.

TREATMENT OF RAISED INTRACRANIAL PRESSURE (ICP)

Raised ICP in the absence of any easily treatable condition (e.g. intracranial haematoma or raised pCO₂) requires careful management. The various techniques used to lower ICP have already been described (pages 83–84) but these must not be applied indiscriminately.

Recent studies show that even in a modern ITU head injured patient are still at risk of sustaining potentially harmful “insults” to the brain in the first few days after head injury from high ICP, low BP, low cerebral perfusion pressure (CPP), hypoxaemia, hypoglycaemia or raised temperature.

Most believe that both raised ICP and reduced cerebral perfusion pressure (CPP) can exacerbate brain damage. What is less clear is whether treatment should focus on lowering ICP or increasing CPP. When autoregulation is impaired, raising CPP beyond 70 mmHg could cause harm. The blind use of hyperventilation in the past to lower ICP by causing vasoconstriction and reduced intracranial blood volume has now been recognised to produce worse outcomes by aggravating cerebral ischaemia.

Patient selection for ICP monitoring: Monitoring ICP and CPP is most relevant in patients with a flexion response to painful stimuli or worse (a response of ‘localising to pain’ signifies a milder degree of injury and spontaneous recovery is likely). Such patients may have already undergone removal of an intracranial haematoma or may have had no mass lesion on CT scan (i.e.: diffuse injury or contusional damage). Each neurosurgical unit is likely to have its own policy for ICP monitoring but the following outline may serve as a guide for patients with no intracranial mass lesion –

DIFFUSE BRAIN DAMAGE/NEGATIVE CT SCAN

A proportion of patients have no intracranial haematoma on CT scan or have only a small haematoma or contusion without mass effect.

In these patients, coma or impairment of conscious level may be due to:

Several of these factors may coexist and contribute to brain damage in patients with intracranial haematoma.

The management principles outlined above apply; in particular it is essential to ensure that respiratory function is adequate and that cerebral perfusion pressure is maintained.

Fat emboli usually occur a few days after injury and may be related to fracture manipulation; deterioration of respiratory function usually accompanies cerebral damage and most patients require ventilation.

Meningitis may occur several days after injury in the presence of basal fractures.

Cerebral swelling may occur at any time after injury and cause a rise in intracranial pressure.

REPEAT CT SCANNING

Occasionally, small areas of ‘insignificant’ contusion on an initial CT scan may develop into a space-occupying haematoma requiring evacuation. Following haematoma evacuation, recollection may occur in 5–10% of cases.

DEPRESSED SKULL FRACTURE

This injury is caused by a blow from a sharp object. Since diffuse ‘deceleration’ damage is minimal, patients seldom lose consciousness.

SIMPLE DEPRESSED FRACTURE (closed injury)

There is no overlying laceration and no risk of infection. Operation is not required except for cosmetic reasons. Removal of any bone spicules imbedded in brain tissue does not reverse neuronal damage.

COMPOUND DEPRESSED FRACTURE (open injury)

A scalp laceration is related to (but does not necessarily overlie) the depressed bone segments. A compound depressed fracture with an associated dural tear may result in meningitis or cerebral abscess.

Investigation

Double density appearance on skull X-ray suggests depression but tangential views may be required to establish the diagnosis. Impairment of conscious level or the presence of focal signs indicate the need for a CT scan to exclude underlying extradural haematoma or severe cortical contusion. Selecting bone window levels on CT scan will clearly demonstrate any depressed fragments.

Management

Treatment aims to minimise the risk of infection. The wound is debrided and the fragments elevated within 24 hours from injury. Bone fragments are either removed or replaced after washing with antiseptic. Antibiotics are not essential unless the wound is excessively dirty.

If the venous sinuses are involved in the depressed fracture, then operative risks from excessive bleeding may outweigh the risk of infection and antibiotic treatment alone is given.

Complications

Most patients make a rapid and full recovery, but a few develop complications:

Infection: May lead to meningitis or abscess formation. Some believe that operation does not reduce the infection risk and advocate a conservative approach unless contamination is severe.

Epilepsy: Early epilepsy (in the first week) occurs in 10% of patients with depressed fracture. Late epilepsy develops in 15% overall, but is especially common when the dura is torn, when focal signs are present, when post-traumatic amnesia exceeds 24 hours or when early epilepsy has occurred (the risk ranges from 3 to 60%, depending on the number of the above factors involved). Elevation of the bone fragments does not alter the incidence of epilepsy.

DELAYED EFFECTS OF HEAD INJURY

POST-TRAUMATIC EPILEPSY

Early epilepsy (occurring within the first week from injury)

Early epilepsy occurs in 5% of patients admitted to hospital with non-missile (i.e. deceleration) injuries. It is particularly frequent in the first 24 hours after injury. Focal seizures are as common as generalised seizures. Status epilepticus occurs in 10%.

The risk of early epilepsy is high in

– children under 5 years.

– patients with prolonged post-traumatic amnesia

– patients with an intracranial haematoma

– patients with a compound depressed fracture.

Late epilepsy (occurring after the first week from injury)

Late epilepsy also occurs in about 5% of all patients admitted to hospital after head injury. It usually presents in the first year, but in some the first attack occurs as long as 10 years from the injury. Late epilepsy is prevalent in patients with

– early epilepsy (25%)

– intracranial haematoma (35%)

– compound depressed fracture (17%).

Prophylactic anticonvulsants appear to be of little benefit in preventing the development of an epileptogenic focus. Management is discussed on page 102.

CEREBROSPINAL FLUID (CSF) LEAK

After head injury a basal fracture may cause a fistulous communication between the CSF space and the paranasal sinuses or the middle ear. Profuse CSF leaks (rhinorrhoea or otorrhoea) are readily detectable, but brain may partially plug the defect and the leak may be minimal or absent. Patients risk developing meningitis particularly in the first week, but in some this occurs after several years. When this is associated with anterior fossa fractures, it is usually pneumococcal; when associated with fractures through the petrous bone, a variety of organisms may be involved.

Clinical signs of a basal fracture have previously been described (page 222). The patient may comment on a ‘salty taste’ in the mouth. Anosmia suggests avulsion of the olfactory bulb from the cribriform plate.

Management

*A Cochrane Review has concluded that evidence does not support the use of prophylactic antibiotics. Prophylactic antibiotics only encourage resistance and late attacks of meningitis may still occur despite their use.

(Lancet (1994) 344:1547–1551)

Preoperative investigations

Coronal high definition CT scanning should identify the fracture site.

CT cisternography – CT scanning after running contrast injected into the lumbar theca, up to the basal cisterns may identify the exact site of the leak.

CSF isotope infusion studies combined with pledget insertion into the nasal recesses may also be of value, but results can be misleading.

Operation

As fractures of the anterior fossa often extend across the midline, a bifrontal exploration is required. The dural tear is repaired with fascia lata, pericranium or synthetic dural substitute. A CSF leak through the middle ear requires a subtemporal approach.

Failure to repair a CSF fistula may result from impaired CSF absorption with an intermittent or persistent elevation of ICP. In these patients a CSF shunt may be required.

POSTCONCUSSIONAL SYMPTOMS

Even after relatively minor head injury, patients may have persistent symptoms of:

– headache, dizziness and increased irritability

– difficulty in concentration and in coping with work

– fatigue and depression.

This condition was once thought to have a purely psychological basis, but it is now recognised that in an injury of sufficient severity to cause loss of consciousness, or a period of post-traumatic amnesia, some neuronal damage occurs; studies show a distinct delay in information processing in these patients, requiring several weeks to resolve. Vestibular ‘concussion’ (end-organ damage) may contribute to the symptomatology (‘dizziness’ and vertigo).

CUMULATIVE BRAIN DAMAGE

The effects of repeated neuronal damage are cumulative; when this exceeds the capacity for compensation, permanent evidence of brain damage ensues. The ‘punch-drunk’ state is well recognised in boxers; dementia may also occur from repeated head injury in jockeys.

CRANIAL NERVE DAMAGE

Cranial nerve damage occurs in about one-third of patients with severe head injury, but treatment is seldom of benefit. These lesions may contribute towards the patient’s residual disability.

OUTCOME AFTER SEVERE HEAD INJURY

Head injury remains a major cause of disability and death, especially in the young. Of those patients who survive the initial impact and remain in coma for at least 6 hours, approximately 40% die within 6 months. The extent of recovery in the remainder depends on the severity of the injury. Residual disabilities include both mental (impaired intellect, memory and behavioural problems) and physical defects (hemiparesis and dysphasia). Most recovery occurs within the first 6 months after injury, but improvement may continue for years. Physiotherapy and occupational therapy play an important role not only in minimising contractures and improving limb power and function but also in stimulating patient motivation.

Outcome is best categorised with the Glasgow Outcome Scale (GOS – see page 214) which uses dependence to differentiate between intermediate grades. After severe injury, about 40% regain an independent existence and may return to premorbid social and occupational activities. Inevitably some remain severely disabled requiring long term care, but few (< 2%) are left in a vegetative state with no awareness or ability to communicate with their environment (see page 214). Prognosis in this group is marginally better than for non-traumatic coma – with about one-third of those vegetative at one month regaining consciousness within one year; of those who regain consciousness, over two-thirds either subsequently die or remain severely disabled. Of those vegetative at 3 months after the injury, none regain an independent existence.

Prognostic features following traumatic coma

The duration of coma relates closely to the severity of injury and to the final outcome, but in the early stages after injury the clinician must rely on other features – age, eye opening, verbal and motor responses, pupil response and eye movements.

	Poor outcome (GOS 1–3)	Favourable outcome (GOS 4–5)
Patients in coma for > 6 hours	61%	39%
Best Glasgow Coma Score > 11	18%	82%
Best Glasgow Coma Score 8–10	32%	68%
Best Glasgow Coma Score < 8	73%	27%
Pupillary response – reacting	50%	50%
Pupillary response – non-reacting	96%	4%
Age < 20 years	41%	59%
Age > 60 years	94%	6%

CHRONIC SUBDURAL HAEMATOMA

Subdivision of subdural haematomas into acute and subacute forms serves no practical purpose. Chronic subdural haematoma however is best considered as a separate entity, differing both in presentation and management.

Predisposing factors

Breakdown of protein within the haematoma and a subsequent rise in osmotic pressure was originally believed to account for the gradual enlargement of the untreated subdural haematoma. Studies showing equality of osmotic pressures in blood and haematoma fluid cast doubt on this theory and recurrent bleeding into the cavity is now known to play an important role.

Clinical features tend to be non-specific.

– Dementia.

– Deterioration in conscious level, occasionally with fluctuating course.

– Symptoms and signs of raised ICP.

– Focal signs occasionally occur, especially limb weakness. This may be ipsilateral to the side of the lesion, i.e. a false localising sign (see page 224).

Diagnosis

CT Scan appearances depend on the time between the injury and the scan.

With injuries 1–3 weeks old, the subdural haematoma may be isodense with brain tissue. In this instance, i.v. contrast enhancement may delineate the cortical margin.

Beyond 3 weeks subdural haematomas appear as a low density lesion.

If CT scan shows midline shift without any obvious extra- or intracerebral lesion, look at the shape of the ventricles.

Management

CEREBROVASCULAR DISEASES

Vascular diseases of the nervous system are amongst the most frequent causes of admission to hospital. The annual incidence in the UK varies regionally between 150–200/100 000, with a prevalence of 600/100 000 of which one-third are severely disabled.

Better control of hypertension, reduced incidence of heart disease and a greater awareness of all risk factors have combined to reduce mortality from stroke. Despite this, stroke still ranks third behind heart disease and cancer as a cause of death in affluent societies.

RISK FACTORS

Prevention of cerebrovascular disease is more likely to reduce death and disability than any medical or surgical advance in management. Prevention depends upon the identification of risk factors and their correction. Increasing age is the strongest risk factor (but is not amenable to correction).

Hypertension

Hypertension is a major factor in the development of thrombotic cerebral infarction and intracranial haemorrhage.

There is no critical blood pressure level; the risk is related to the height of blood pressure and increases throughout the whole range from normal to hypertensive. A 6 mmHg fall in diastolic blood pressure is associated in relative terms with a 40% fall in the fatal and non-fatal stroke rate.

Systolic hypertension (frequent in the elderly) is also a significant factor and not as harmless as previously thought.

Cardiac disease

Cardiac enlargement, failure and arrhythmias, as well as rheumatic heart disease, patent foramen ovale and, rarely, cardiac myxoma are all associated with an increased risk of stroke.

Diabetes

The risk of cerebral infarction is increased twofold in diabetes. More effective treatment of diabetes has not reduced the frequency of atherosclerotic sequelae.

Heredity

Close relatives are at only slightly greater risk than non-genetically related family members of a stroke patient. Diabetes and hypertension show familial propensity thus clouding the significance of pure hereditary factors.

Blood lipids, cholesterol, smoking, diet/obesity

These factors are much less significant than in the genesis of coronary artery disease.

Race

Alterations in life style, diet and environment probably explain the geographical variations more than racial tendencies.

Haematocrit

A high blood haemoglobin concentration (or haematocrit level) is associated with an increased incidence of cerebral infarction. Other haematological factors, such as decreased fibrinolysis, are important also.

Oral contraceptives

Combined oral contraception (COC) containing high dose oestrogen increased the risk of thrombosis, including stroke. The effect of low dose oestrogen COC is less clear.

CEREBROVASCULAR DISEASE – MECHANISMS

‘Stroke’ is a generic term, lacking pathological meaning. Cerebrovascular diseases can be defined as those in which brain disease occurs secondary to a pathological disorder of blood vessels (usually arteries) or blood supply.

CEREBROVASCULAR DISEASE – NATURAL HISTORY

Approximately one-third of all ‘strokes’ are fatal. The age of the patient, the anatomical size of the lesion, the degree of deficit and the underlying cause all influence the outcome.

Immediate outcome

In cerebral haemorrhage, mortality approaches 50%.

Cerebral infarction fares better, with an immediate mortality of less than 20%, fatal lesions being large with associated oedema and brain shift.

Embolic infarction carries a better outcome than thrombotic infarction.

Fatal cases of infarction die either at onset, within a few days because of cytotoxic cerebral oedema or later from cardiovascular or respiratory complications.

The level of consciousness on admission to hospital gives a good indication to immediate outcome. The deeper the conscious level the graver the prognosis.

Long-term outcome

The prognosis following infarction due to thrombosis or embolisation from diseased neck vessels or heart is dependent on the progression of the underlying atherosclerotic disease. Recurrent cerebral infarction rates vary between 5% and 15% per year. Symptoms of coronary artery disease and/or peripheral vascular disease may also ensue. Five year mortality is 44% for males and 36% for females.

The long-term prognosis following survival from haemorrhage depends upon the cause and the treatment.

CEREBROVASCULAR DISEASE – CAUSES

EMBOLISATION (25%) from:

DISEASES OF BLOOD

e.g. Coagulopathies or Haemoglobinopathies

CEREBRAL VENOUS THROMBOSIS

Thrombosis of cerebral veins may occur with infection, dehydration or in association with oestrogen excess, either post-partum or combined oral contraceptive use.

DECREASED CEREBRAL PERFUSION

Hypotension, from cardiac arrhythmia or GI bleed, can lead to infarction in the watershed between arterial territories.

HAEMORRHAGE (20%)

Into the brain substance – parenchymal (15%) and/or subarachnoid space (5%)	Neoplasm
	Coagulation disorder e.g. haemophilia
Hypertension	Anticoagulant therapy
Amyloid vasculopathy	Vasculitis
Aneurysm	Drug abuse e.g. cocaine
Arteriovenous malformation	Trauma

OCCLUSIVE AND STENOTIC CEREBROVASCULAR DISEASE

PATHOLOGY

The normal vessel wall comprises:

Within brain and spinal cord tissue the adventitia is usually very thin and the elastic lamina between media and adventitia less apparent.

The intima is an important barrier to leakage of blood and constituents into the vessel wall. In the development of the atherosclerotic plaque, damage to the endothelium of the intima is the primary event.

The atherosclerotic plaque

Following intimal damage:

Haemorrhage may occur within the plaque or the plaque may ulcerate into the lumen of the vessel forming an intraluminal mural thrombus. Either way, the lumen of the involved vessel is narrowed (stenosed) or blocked (occluded).

The plaque itself may give rise to emboli. Cholesterol is present partly in crystal form and fragments following plaque rupture may be sufficiently large to occlude the lumen of distal vessels. The cholesterol esters, lipids and phospholipids each play a role in the aggregation of such emboli.

The carotid bifurcation in the neck is a frequent site at which the antheromatous plaque causes stenosis or occlusion.

Platelet emboli arise from thrombus developed over the damaged endothelium. This thrombus is produced partly by platelets coming into contact with exposed collagen fibres. Endothelial cells synthesise PROSTACYCLIN which is a potent vasodilator and inhibitor of platelet aggregation. THROMBOXANE A2, synthesised by platelets, has opposite effects. In thrombus formation these two PROSTAGLANDINS actively compete with each other.

CEREBROVASCULAR DISEASE – PATHOPHYSIOLOGY

Standard techniques of cerebral blood flow (CBF) measurement provide information on both global and regional flow in patients with cerebral ischaemia or infarction. Recent availability of positron emission tomography (PET), recording oxygen and glucose metabolism, as well as blood flow and blood volume, gives a more detailed and accurate understanding of pathophysiological changes after stroke.

Changes in cerebral infarction

Pathophysiology of ischaemia

Progression from reversible ischaemia to infarction depends upon the degree and duration of the reduced blood flow.

Ischaemic cascade

A significant fall in cerebral blood flow produces a cascade of events which, if unchecked, lead to the production and accumulation of toxic compounds and apoptosis (programmed cell death).

Role of neurotransmitters

In addition to the cascade outlined above one of the amino acid excitatory neurotransmitters, Glutamate, in excess is a powerful neurotoxin, which plays an important role in ischaemic brain damage.

There have been numerous agents that interfere with different steps in this complicated series of interactions with an ultimate aim of providing neuroprotection and limiting the size of the stroke. Despite numerous trials of more than 100 different agents no drug has been developed that provides neuroprotection in man.

TRANSIENT ISCHAEMIC ATTACKS (TIAs)

Transient ischaemic attacks are episodes of focal neurological symptoms due to inadequate blood supply to the brain. Attacks are sudden in onset, resolve within 24 hours or less and leave no residual deficit. These attacks are important as warning episodes or precursors of cerebral infarction.

Before diagnosing TIAs, consider other causes of transient neurological dysfunction – migraine, partial seizures, hypoglycaemia, syncope and hyperventilation.

The pathogenesis of transient ischaemic attacks

A reduction of cerebral blood flow below 20–30 ml/100 g/min produces neurological symptoms. The development of infarction is a consequence of the degree of reduced flow and the duration of such a reduction. If flow is restored to an area of brain within the critical period, ischaemic symptoms will reverse themselves. TIAs may be due to:

Both mechanisms occur. Emboli are accepted as the cause of the majority of TIAs.

The symptomatology of TIAs

A small number of transient ischaemic attacks are difficult to fit convincingly into either anterior or posterior circulation, e.g. dysarthria with hemiparesis.

The natural history of TIAs

Following a TIA, 5% of patients will develop infarction within 1 week and 12% within 3 months. The risk of infarction is greatest in older patients with more risk factors (hypertension and diabetes) who have had longer hemispheric TIAs. About 10% of patients who have a stroke have had a warning TIA.

CLINICAL SYNDROMES – LARGE VESSEL OCCLUSION

OCCLUSION OF THE INTERNAL CAROTID ARTERY – may present in a ‘stuttering’ manner due to progressive narrowing of the lumen or recurrent emboli.

The degree of deficit varies – occlusion may be asymptomatic and identified only at autopsy, or a catastrophic infarction may result.

The origins of the vessels from the aortic arch are such that an innominate artery occlusion will result not only in the clinical picture of carotid occlusion but will produce diminished blood flow and hence blood pressure in the right arm.

The outcome of carotid occlusion depends on the collateral blood supply primarily from the circle of Willis, but, in addition, the external carotid may provide flow to the anterior and middle cerebral arteries through meningeal branches and retrogradely through the ophthalmic artery to the internal carotid artery.

MIDDLE CEREBRAL ARTERY

Anatomy

The middle cerebral artery is the largest branch of the internal carotid artery. It gives off (1) deep branches (perforating vessels – lenticulostriate) which supply the anterior limb of the internal capsule and part of the basal nuclei. It then passes out to the lateral surface of the cerebral hemisphere at the insula of the lateral sulcus. Here it gives off cortical branches (2) temporal, (3) frontal, (4) parietal.

Clinical features

The middle cerebral artery may be occluded by embolus or thrombus. The clinical picture depends upon the site of occlusion and whether dominant or non-dominant hemisphere is affected.

Occlusion at the insula

When cortical branches are affected individually, the clinical picture is less severe, e.g. involvement of parietal branches alone may produce Wernicke’s dysphasia with no limb weakness or sensory loss.

The deep branches (perforating vessels) of the middle cerebral artery may be a source of haemorrhage or small infarcts (lacunes – see later).

VERTEBRAL ARTERY OCCLUSION

Anatomy

The vertebral artery arises from the subclavian artery on each side. Underdevelopment of one vessel occurs in 10%.

The vertebral artery runs from its origin through the foramen of the transverse processes of the mid-cervical vertebrae. It then passes laterally through the transverse process of the axis, then upwards to the atlas accompanied by a venous plexus and across the suboccipital triangle to the vertebral canal. After piercing the dura and arachnoid matter, it enters the cranial cavity through the foramen magnum. At the lower border of the pons, it unites with its fellow to form the basilar artery.

The vertebral artery and its branches supply the medulla and the inferior surface of the cerebellum before forming the basilar artery.

Clinical features

Occlusion of the vertebral artery, when low in the neck, is compensated by anastomotic channels.

When one vertebral artery is hypoplastic, occlusion of the other is equivalent to basilar artery occlusion.

Only the posterior inferior cerebellar artery (PICA) depends solely on flow through the vertebral artery. Vertebral artery occlusion may therefore present as a PICA syndrome (page 255).

The close relationship of the vertebral artery to the cervical spine is important. Rarely, damage at intervertebral foramina or the atlanto-axial joints following subluxation may result in intimal damage, thrombus formation and embolisation.

Vertebral artery compression during neck extension may cause symptoms of intermittent vertebrobasilar insufficiency.

BASILAR ARTERY OCCLUSION

Anatomy

The basilar artery supplies the brain stem from medulla upwards and divides eventually into posterior cerebral arteries as well as posterior communicating arteries which run forward to join the anterior circulation (circle of Willis).

Branches can be classified into:

1. Posterior cerebral arteries

2. Long circumflex branches

3. Paramedian branches.

Clinical features

Prodromal symptoms are common and may take the form of diplopia, visual field loss, intermittent memory disturbance and a whole constellation of other brain stem symptoms:

The complete basilar syndrome following occlusion consists of:

– impairment of consciousness → coma

– bilateral motor and sensory dysfunction

– cerebellar signs

– cranial nerve signs indicative of the level of occlusion.

The clinical picture is variable. Occasionally basilar thrombosis is an incidental finding at autopsy.

‘Top of basilar’ occlusion: This results in lateral midbrain, thalamic, occipital and medial temporal lobe infarction. Abnormal movements (hemiballismus) are associated with visual loss, pupillary abnormalities, gaze palsies, impaired conscious level and disturbances of behaviour.

Paramedian perforating vessel occlusion gives rise to the ‘LOCKED-IN’ SYNDROME (page 256) and LACUNAR infarction (page 257).

POSTERIOR CEREBRAL ARTERY

Anatomy

The posterior cerebral arteries are the terminal branches of the basilar artery. Small perforating branches supply midbrain structures, choroid plexus and posterior thalamus. Cortical branches supply the undersurface of the temporal lobe – temporal branch; and occipital and visual cortex – occipital and calcarine branches.

Clinical features

Proximal occlusion by thrombus or embolism will involve perforating branches and structures supplied:

Midbrain syndrome – III nerve palsy with contralateral hemiplegia – WEBER’s SYNDROME

Thalamic syndromes – chorea or hemiballismus with hemisensory disturbance.

Occlusion of cortical vessels will produce a different picture with visual field loss (homonymous hemianopia) and sparing of macular vision (the posterior tip of the occipital lobe, i.e. the macular area, is also supplied by the middle cerebral artery).

Posterior cortical infarction in the dominant hemisphere may produce problems in naming colours and objects.

CLINICAL SYNDROMES – BRANCH OCCLUSION

BASILAR ARTERY – PARAMEDIAN BRANCH OCCLUSION

At the midbrain level damage to the nucleus or the fasciculus of the oculomotor nerve (III) will result in a complete or partial III nerve palsy; damage to the red nucleus (outflow from opposite cerebellar hemisphere) will also produce contralateral tremor – referred to as BENEDIKT’S SYNDROME.

At the pontine level an abducens nerve (VI) palsy will occur with ipsilateral facial (VII) weakness and contralateral sensory loss – light touch, proprioception (medial lemniscus damage)when the lesion is more basal.

Abducens and facial palsy may be accompanied by contralateral hemiplegia – MILLARD-GUBLER SYNDROME.

At the medullary level, bilateral damage usually occurs and results in the ‘LOCKED-IN’ SYNDROME. The patient is paralysed and unable to talk, although some facial and eye movements are preserved.

Spinothalamic sensation is retained, but involvement of the medial lemniscus produces loss of ‘discriminatory’ sensation in the limbs. The syndrome usually follows basilar artery occlusion and carries a grave prognosis.

CLINICAL SYNDROMES – LACUNAR STROKE (LACI)

Occlusion of deep penetrating arteries produces subcortical infarction characterised by preservation of cortical function – language, other cognitive and visual functions.

Clinical syndromes are distinctive and normally result from long-standing hypertension. In 80%, infarcts occur in periventricular white matter and basal ganglia, the rest in cerebellum and brain stem. Areas of infarction are 0.5 –1.5cm in diameter and occluded vessels demonstrate lipohyalinosis, microaneurysm and microatheromatous changes. Lacunar or subcortical infarction accounts for 17% of all thromboembolic strokes and knowledge of commoner syndromes is essential.

Sensorimotor syndromes are common although anatomical basis is obscure. A recent Stroke Data Bank survey showed the commonest presentations to be:

Pure motor hemiplegia 57%

Sensorimotor 20%

Ataxic hemiparesis 10%

Pure sensory 7%

Dysarthria/Clumsy hand 6%

Investigations MRI is superior to CT demonstrating lacunae, although either may occasionally misdiagnose a small resolving haematoma. Confirmation of lacunar stroke may save patients from unnecessary investigations for carotid and cardiac embolic source.

Prognosis For all syndromes this is encouraging. Careful control of blood pressure and the use of aspirin usually prevents recurrence. Multiple lacunar infarctions – ‘état lacunaire’ – results in shuffling gait, pseudobulbar palsy and subcortical dementia.

CLASSIFICATION OF SUBTYPES OF CEREBRAL INFARCTION

A recently devised classification of infarction has proved simple and of practical value in establishing diagnosis and in predicting outcome –

	Clinical features	Outcome
Total Anterior Circulation	motor and sensory deficit, hemianopia and disturbance of higher cerebral function	Poor
Syndrome (TACS)
Partial Anterior Circulation	any two of above	Variable
Syndrome (PACS)	or isolated disturbance of cerebral function
Posterior Circulation	signs of brain stem dysfunction	Variable
Syndrome (POCS)	or isolated hemianopia
Lacunar Anterior	pure motor stroke	Good
Circulation Syndrome (LACS)	or pure sensory stroke
	or pure sensorimotor stroke
	or ataxic hemiparesis

EMBOLISATION

Emboli consist of friable atheromatous material, platelet-fibrin clumps or well formed thrombus.

The diagnosis of embolic infarction depends on:

• The identification of an embolic source, e.g. cardiac disease.

• The clinical picture of sudden onset.

• Infarction in the territory of a major vessel or large branch.

Clinical picture – depends on the vessel involved. Emboli commonly produce transient ischaemic attacks (TIA) as well as infarction.

Symptoms are referable to the eye (retinal artery) and to the anterior and middle cerebral arteries, and take the form of:

Visual loss – transient, i.e. amaurosis fugax or permanent.

Hemisensory and hemimotor disturbance.

Disturbance of higher function, e.g. dysphasia.

Focal or generalised seizures – may persist for some time after the ischaemic episode.

Depression of conscious level if major vessel occlusion occurs.

Emboli less frequently affect the posterior circulation.

EMBOLI FROM THE INTERNAL CAROTID ARTERY AND AORTA

Emboli from these sources are commonest outwith the heart. The majority of all cerebral emboli arise from ulcerative plaques in the carotid arteries (see page 244).

Emboli arising from the aorta (atheromatous plaque or aortic aneurysm) often involve both hemispheres and systemic embolisation (e.g. affecting limbs) may coexist.

EMBOLI OF CARDIAC ORIGIN

Non-bacterial endocarditis (marantic endocarditis): associated with malignant disease due to fibrin and platelet deposition on heart valves.

Atrial myxoma is a rare cause of recurrent cerebral embolisation. Bihemisphere episodes with a persistently elevated ESR should arouse suspicion which may be confirmed by cardiac ultrasound.

Patent foramen ovale may result in paradoxical embolisation; suspect in patient with deep venous thrombosis who develops cerebral infarction. Emboli can also arise from intracardiac thrombus.

New cardiac imaging techniques especially Transoesophageal Echocardiography (TOE) allow a more accurate detection of potential embolic source. Transcranial Doppler (TCD) may characterise emboli by analysing their signals and help quantify risk of recurrence.

EMBOLI FROM OTHER SOURCES

Fat emboli: following fracture, especially of long bones and pelvis, fat appears in the bloodstream and may pass into the cerebral circulation, usually 3 –6 days after trauma. Emboli are usually multiple and signs are diffuse.

Air emboli follow injury to neck/chest, or follow surgery. Rarely, air emboli complicate therapeutic abortion. Again the picture is diffuse neurologically. Onset is acute; if the patient survives the first 30 minutes, prognosis is excellent.

Nitrogen embolisation or decompression sickness (the ‘bends’) produces a similar picture, but if the patient survives, neurological disability may be profound.

Tumour emboli result in metastatic lesions; the onset is usually slow and progressive. Acute stroke-like presentation may occur, followed weeks or months later by the mass effects.

STENOTIC/OCCLUSIVE DISEASE – INVESTIGATIONS

1. CONFIRM THE DIAGNOSIS

Magnetic resonance imaging (MRI)

T2 prolongation (hyperintensity in relation to white and grey matter) occurs within hours of onset of ischaemic symptoms. Advanced techniques, diffusion weighted imaging (DWI) and perfusion imaging (PWI) show respectively early infarction (cytotoxic oedema) and ischaemic tissue at risk (the ischaemic penumbra). These advanced techniques are valuable predictors of outcome and guide treatments directed as ‘ischaemic salvage’ e.g. thrombolysis.

2. DEMONSTRATE THE SITE OF PRIMARY LESION

(a) Non-invasive investigation

Ultrasound – Doppler/Duplex scanning: assesses extra- and intracranial vessels (page 44). A normal study precludes the need for angiography.

Cardiac ultrasound (transthoracic or transoesophageal): this often reveals a cardiac embolic source in young people with stroke, e.g. prolapsed mitral valve, patent foramen ovale.

Magnetic resonance angiography (MRA)

‘Time of flight’ or contrast enhanced techniques are used. Whilst of value in patients with heavily calcified carotid plaques, resistant to Doppler, it tends to overestimate the severity of stenosis. When assessing the carotid arteries it is best used in combination with Doppler. Its non-invasive nature makes it helpful in investigating the intracranial circulation.

Computed tomographic angiography (CTA)

Dynamic helical CT, following bolus injection of non-ionic contrast, can be used to investigate both intracranial and extracranial vasculature. CTA compared with DSA correctly classifies the degree of carotid stenosis in 96% of cases but is insensitive to ulcerative plaque. Again it is best used in conjunction with Doppler.

(b) Digital intravenous subtraction angiography (DSA)

The combination of the above techniques has decreased the need for invasive investigation but cerebral angiography may still be required to make a definitive diagnosis.

Indications of angiography

1. In those patients with anterior circulation TIA or minor stroke if non-invasive techniques have not clarified the nature and degree of carotid stenosis.

2. In patients where unusual aetiologies are suspected and less invasive imaging has not been diagnostic – for example young patients or when cerebral vasculitis is suspected.

3. IDENTIFY FACTORS WHICH MAY INFLUENCE TREATMENT AND OUTCOME

General investigations identify conditions which may predispose towards premature cerebrovascular disease. These are essential in all patients.

Chest x-ray – cardiac enlargement – hypertension/valvular heart disease

ECG – ventricular enlargement and/or arrhythmias – hypertension/embolic disease recent myocardial infarct – embolic disease sinoatrial conduction defect – embolic disease/output failure

Blood glucose – diabetes mellitus

Serum lipids and cholesterol – hyperlipidaemia

VDRL-TPHA – neurosyphilis

Prothrombin time – circulating auto-anticoagulants

Partial thromboplastin time (PTT) – prolonged by lupus anticoagulant

Note drug history – oral contraceptives, amphetamines, opiates

Following the interpretation of these preliminary investigations, more detailed studies may be required, e.g.

– anticardiolipin antibodies – antiphospholipid syndrome

– muscle biopsy – mitochondrial disease

CEREBRAL INFARCTION – MANAGEMENT

THE ACUTE STROKE

Clinical history, examination and investigation will separate infarction and haemorrhage. Once the nature of the ‘stroke’ has been confidently defined, treatment should be instigated. The treatment of stroke has been the subject of many clinical trials and the following is a digest of the current advice based on those studies.

Treatment aims

– Recanalise blocked vessels

– Prevent progression of present event

– Prevent immediate complication

– Prevent the development of subsequent events

– Rehabilitate the patient.

General measures

Specific measures

Patients not eligible for thrombolysis

Give aspirin 300 mg daily for 2 weeks or clopidogrel in aspirin intolerant patients. Anticoagulants should be avoided if possible as they increase the risk of deterioration from haemorrhagic transformation.

Transfer to stroke unit

There is good evidence that multidisciplinary care on a stroke unit improves the outcome of patients with stroke.

Assess swallow

Aspiration pneumonia is a significant complication after stroke. Minimise this risk by assessing swallowing and using a nasogastric tube for fluids and food if swallowing unsafe.

Early mobilisation

Help patients sit up when possible and mobilise early.

Special situations

Decompressive hemicraniectomy

A small number of young patients (<60) with large middle cerebral artery strokes deteriorate after 24–72 hours from massive cytotoxic cererbral oedema which is resistant to medical therapy. Surgical decompression can save life, allowing many patients to make reasonable recoveries.

Other neurosurgical interventions

Patients with large cerebellar infarcts can deteriorate 24–48 hours after their stroke when oedema leads to compression of the posterior fossa and associated hydrocephalus. Posterior fossa decompression can be life saving and many patients then make good recoveries.

Prevention of further stroke

The recognition of risk factors and their correction to minimise the risk of further events forms a necessary and important step in long-term treatment.

The strategies here are the same as those used for treatment for patients with TIA (see below).

– Control hypertension

– mphasise the need to stop cigarette smoking

– Correct lipid abnormality

– Give platelet antiaggregation drugs (aspirin or in selected cases Dipyridamole or Clopidogrel) to reduce the rate of reinfarction

– Remove or treat embolic source (long term anticoagulation in atrial fibrillation). Defer anticoagulation in disabling stroke for 2 weeks as risk of haemorrhage outweighs benefit.

– Treat inflammatory or vascular inflammatory diseases

– Stop thrombogenic drugs, e.g. oral contraceptives.

TIAs AND MINOR INFARCTION – MANAGEMENT

The aim of treatment is to prevent subsequent cerebral infarction:

Establish diagnosis and exclude other pathologies causing transient neurological symptoms, e.g. migraine.

Correct predisposing condition.

Examine patient for evidence of extracranial vascular disease:

Palpate carotids, upper limb pulses. Auscultate the neck for bruits.

Check blood pressure in both arms. Examine heart.

Medical treatment

Prevention of a further cerebrovascular event (secondary prevention) depends on the cause, which for almost all patients is atherosclerosis – Stop smoking, control diabetes, reduce, cholesterol or blood pressure, even if the levels are in the normal range.

Adding dipyridamole with aspirin reduces the risk further. Clopidogrel has a similar effect to aspirin.

Special situations:

Atrial fibrillation – high risk of recurrence (12%) is reduced to approximately 4% by oral anticoagulation.

Surgical and other interventional treatments

Carotid stenosis – high quality surgical studies demonstrated that patients with carotid stenosis >70% (though not with occlusion) and a TIA or small stroke in carotid territory have a lower risk of further stroke if they undergo a carotid endarterectomy. This benefit depends on the procedure being done by an experienced surgeon with low rate of complications. The risk of stroke, and thus the benefit of surgery is highest with higher grades of stenosis and in patients with hemisphere TIA (as opposed to amaurosis fugax). The risk of complications for patients with lower degrees of stenosis outweighs the benefit.

Carotid angioplasty and stenting is an alternative to carotid endarterectomy in patients with stenosis of >70% but recent studies have found a higher risk of late recurrence than for surgery, The role for these interventions in vertebrobasilar stenosis is not yet established.

Other surgical interventions, for example the superficial temporal to middle cerebral artery bypass provide no benefit.

HYPERTENSION AND CEREBROVASCULAR DISEASE

Next to age, the most important factor predisposing to cerebral infarction or haemorrhage is hypertension. The risk is equal in males and females and is proportional to the height of blood pressure (diastolic and systolic).

The pathological effects of sustained hypertension are:

– Charcot Bouchard microaneurysms → INTRACEREBRAL HAEMORRHAGE (from perforating vessels)

– Accelerated atheroma and thrombus formation → INFARCTION (large vessels)

– Hyalinosis and fibrin deposition → INFARCTION (lacunes – small vessels)

HYPERTENSIVE ENCEPHALOPATHY

An acute, usually transient, cerebral syndrome precipitated by sudden severe hypertension. The excessive blood pressure may be due to malignant hypertension from any cause, or uncontrolled hypertension in glomerulonephritis, pregnancy (eclampsia) or phaeochromocytoma.

The mechanism is complex: Cerebral resistance vessels

Clinical features: Headache and confusion precede convulsions and coma. Papilloedema with haemorrhages and exudates are invariably found. Proteinuria and signs of renal and cardiac failure are common.

Diagnosis: CT scanning shows a widespread white matter low attenuation and excludes other pathology. MRI confirms increased brain water content and SPECT shows hyperperfusion adjacent to these changes.

Treatment: a precipitous fall in blood pressure can result in retinal damage and watershed infarction. Gradually reduce blood pressure with i.v. nitroprusside or hydralazine. Reserve peritoneal dialysis for resistant cases.

N.B. With treatment full recovery is usual. Without treatment death occurs.

BINSWANGER’S ENCEPHALOPATHY (Subcortical arteriosclerotic encephalopathy – SAE)

A rare disorder in which progressive dementia and pseudobulbar palsy are associated with diffuse hemisphere demyelination. The CT scan shows areas of periventricular low attenuation, often also involving the external capsule. The pathological changes were previously attributed to chronic diffuse oedema, but the recent finding of a high plasma viscosity in these patients suggests that this, in conjunction with hypertensive small vessel disease, could produce chronic ischaemic change in central white matter.

Subclinical forms of this disease may exist as this CT scan appearance is occasionally found in asymptomatic patients.

MRI appears more sensitive in establishing radiological diagnosis.

NON-ATHEROMATOUS CEREBROVASCULAR DISEASE

ABNORMALITIES OF EXTRACRANIAL VESSELS

SPONTANEOUS AND TRAUMATIC ARTERIAL DISSECTION

Extracranial and intracranial dissections are an underdiagnosed cause of stroke in young persons. Spontaneous dissections occur in Marfan’s syndrome or collagen disorders (Ehlers–Danlos), but more frequently in patients with no clear risk factors. Whilst there may be a clear history of neck trauma, often the trauma is minor (eg a sneeze). This may lead to dissection and stenosis or occlusion. The vertebral arteries are particularly susceptible to trauma in view of their close relationship to the cervical spine at intervertebral foramina, the atlanto-axial joint and the occipito-atlantal joint. Carotid dissection may present with a painful isolated Horner’s syndrome or lower cranial nerve palsies. Angiography or CT/MR angiography will confirm. Treatment is with anticoagulation or antiplatelet agents. No studies are available to determine the best treatment strategy.

FIBROMUSCULAR DYSPLASIA

This disease involves intracranial as well as extracranial vessels which appear like a ‘string of beads’. The patient presents with infarction as a result of thrombotic occlusion or from an associated saccular aneurysm, of which there is an increased risk. Transluminal angioplasty can be used to dilate a stenotic segment.

INFLAMMATION VESSEL OCCLUSION

Infection in structures close to the carotid artery can result in inflammatory change in the vessel wall and secondary thrombosis. In children, infection in the retropharyngeal fossa (tonsillar infection) may cause cerebral infarction. Meningitis (especially pneumococcal) may result in secondary arteritis and occlusion of intracerebral vessels as they cross the subarachnoid space.

MOYAMOYA DISEASE

Bilateral occlusion of the carotid artery at the siphon is followed by the development of a fine network of collateral arteries and arterioles at the base of the brain. This may be a congenital or acquired disorder associated with previous meningitis, oral contraception or granulomatous disease (e.g. sarcoidosis). Children present with alternating hemiplegia, adults with subarachnoid haemorrhage. There is no specific treatment though some use surgical revascularisation procedures.

DISEASES OF THE VESSEL WALL

VASCULITIS AND COLLAGEN VASCULAR DISEASES

These disorders have systemic as well as neurological features. Occasionally only the nervous system is diseased. All are rare causes of stroke but need different treatments.

Collagen vascular diseases:

– Systemic lupus erythematosus

– Rheumatoid arthritis

– Other connective tissue disorders.

Mechanism

An immune basis for these disorders is likely.

This is termed IMMUNE COMPLEX VASCULITIS.

Indirect immunofluorescent microscopy on biopsy material will demonstrate the presence of immune complexes.

In giant cell arteritis and granulomatous vasculitis, cellular immune mechanisms are probably to blame and vessels are directly attacked. A reaction of antigen with sensitised lymphocytes results in lymphokine release – attracted mononuclear cells release lysosomal enzymes with resultant granuloma formation.

In all vasculitides affecting predominantly large and medium size vessels, angiography is important in establishing diagnosis. On MRI the presence of bilateral cortical and subcortical infarction is suggestive.

SYSTEMIC LUPUS ERYTHEMATOSUS: in 75% of patients nervous system involvement occurs and may predate systemic manifestation.

– Cranial or peripheral nerve involvement

– SPINAL stroke

– Involuntary movements.

Pathology

The predominant CNS finding is microvascular injury with hyalinisation, perivascular lymphocytosis, endothelial proliferation and thrombosis. Active vasculitis is rare. Cardiogenic embolism and coagulopathy (antiphospholipid antibodies) are alternative mechanisms of stroke.

Treatment

Corticosteroids in moderate dosage. In patients with severe or fulminant disease, immunosuppressants and plasma exchange may help.

POLYARTERITIS NODOSA

Neurological involvement is common (80%): Small and medium size arteries are affected.

– HEMIPLEGIA – microinfarction

– INTRACRANIAL HAEMORRHAGE – aneurysm formation

– SPINAL INFARCTION or HAEMORRHAGE

– Peripheral nerve involvement (mononeuritis multiplex)

Hypertension and renal involvement are common.

Treatment

Steroids and immunosuppressant therapy have dramatically improved outcome (60% 5-year survival).

Plasmapheresis is successful in acute cases.

ALLERGIC ANGIITIS (Hypersensitivity vasculitis)

Intercurrent illnesses (infection or neoplasia) trigger immune complex deposition and basement membranes of capillaries and venules. Systemic symptoms – rash, fever and arthralgia are associated with multiorgan involvement. Neurological features – neuropathy, stroke-like syndromes – occur in 30% of patients. Investigations suggest systemic upset – elevated ESR, anaemia, leukopaenia. Skin biopsy confirms peri-venular inflammation. Treatment of underlying infection and steroids produce rapid improvement.

TAKAYASU’S (PULSELESS) DISEASE

A giant cell arteritis involving the aorta and its major branches. Predominantly affects Asian females in third or fourth decades.

Symptoms:

– Non-specific – fever, arthralgias and myalgia

– Vascular – myocardial ischaemia, peripheral vascular disease

– Neurological vascular TIAs (including subclavian steal), strokes and dementia.

Diagnosis:

Steroids are useful initially. The role of surgical reconstruction of occluded vessels is uncertain

GIANT CELL ARTERITIS (see page 73)

CHURG-STRAUSS ANGIITIS

A distinctive syndrome of eosinophilia, pulmonary infiltrates, neuropathy and encephalopathy or stroke. Related to polyarteritis nodosa, steroid responsive. Other immunosuppressants e.g. cyclophosphamide in resistant cases.

DISEASES OF THE BLOOD

Disorders of the blood may manifest themselves as ‘stroke-like’ syndromes. Examination of the peripheral blood film is an important investigation in cerebrovascular disease. Where indicated, more extensive haematological investigation is necessary.

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Neurological involvement – a diffuse fluctuating encephalopathy, subarachnoid or subdural haemorrhage.

Diagnosis confirmed by – low platelet count – prolonged prothrombin time, elevated fibrin degradation products and reduced fibrinogen levels.

Treatment

Heparin. Fresh frozen plasma/vitamin K. Treatment of underlying cause.

HAEMOGLOBINOPATHIES

These are genetically determined disorders in which abnormal haemoglobin is present in red blood cells.

Sickle cell disease

This disorder is common in people of African origin but also occurs sporadically throughout the Mediterranean and Middle East region.

The patient is of small stature, usually with chronic leg ulcers, cardiomegaly and hepatosplenomegaly. When arterial oxygen saturation is reduced, ‘sickling’ will occur, manifested clinically by abdominal pain/bone pain.

Neurological involvement – hemiparesis, optic atrophy, subarachnoid haemorrhage.

Diagnosis is confirmed in vitro by the ‘sickling’ of cells when O₂ tension is reduced and by haemoglobin electrophoresis.

Treatment

Analgesics for pain O₂ therapy, or hyperbaric O₂. Exchange transfusion should be carried out for those with a severe or progressive deficit.

ANTIPHOSPHOLIPID ANTIBODIES

These IgG or IgM antibodies prolong APTT and appear to be associated with thrombotic stroke. There remains uncertainty as to whether they are caused by or represent a transient non-specific ‘acute phase’ reaction to illness. Such antibodies can be found in patients with systemic lupus erythematosus.

ANTITHROMBIN III, PROTEIN C AND PROTEIN S DEFICIENCY

Deficiency of any of these circulating antithrombotic fibrinolytic agents can result in deep venous thrombosis, pulmonary embolism or cerebral venous sinus thrombosis.

HYPERGAMMAGLOBULINAEMIA

An increase in serum gamma globulin may arise as a primary event or secondary to leukaemia, myeloma, amyloid.

Neurological involvement develops in 20% of cases – due to increased viscosity.

Clinical features are similar to those of polycythaemia – peripheral nervous system involvement may also occur.

Diagnosis is confirmed by protein electrophoresis.

Treatment – underlying cause – plasmapheresis.

THROMBOTIC THROMBOCYTOPENIC PURPURA (syn: Moschkowitz’s syndrome)

This is a fibrinoid degeneration of the subintimal structures of small blood vessels. Lesions occur in all organs including the brain.

Clinical features – fever with purpura and multiorgan involvement and neurological features of diffuse encephalopathy or massive intracranial haemorrhage.

Haemolytic anaemia, haematuria and thrombocytopenia are the main laboratory features.

Treatment

Heparin, steroids and platelet inhibitors may be of value.

THROMBOCYTOPENIA

Whether idiopathic, drug-induced or due to myeloproliferative disorders, this condition may be associated with intracranial haemorrhage.

THROMBOCYTOSIS

This is an elevation in platelet count above 600 000 per mm³. It may be part of a myeloproliferative disorder, or ‘reactive’ to chronic infection. Patients present with recurrent thrombotic episodes.

Treatment

Aspirin in mild cases; plasmapheresis and antimitotic drugs if more severe.

HYPERFIBRINOGENAEMIA

Serum fibrinogen is occasionally elevated in people with cerebrovascular disease. This enhances coagulation and raises blood viscosity. Infection, pregnancy, malignancy and smoking all raise fibrinogen and may explain in part the increased risk of cerebral infarction. Arvin (Malayan viper venom) acutely lowers serum levels.

METABOLIC DISORDERS

HOMOCYSTINURIA

A recessively inherited disorder. Accumulation of homocystine in blood damages endothelium and induces premature occlusive arterial disease. The significance of the heterozygote state is uncertain.

MELAS

See Mitochondrial disorders (page 481).

CEREBROVASCULAR DISEASE – VENOUS THROMBOSIS

The venous sinuses are important in CSF absorption, with arachnoid villi invaginating the sagittal sinus in particular. Thrombotic occlusion of the venous system occurs with

— infection (especially ear or sinus infection)

— dehydration

— pregnancy, puerperium and pill

— coagulation disorders

— malignant meningitis

— miscellaneous disorders e.g. sarcoid, Behçets

Improved imaging (MRI) has resulted in increased recognition. Venous infarction accounts for 1% of all ‘strokes’.

Superior sagittal and lateral sinus thrombosis (85% of cases)

Impaired CSF drainage results in headache, papilloedema and impaired consciousness. Venous infarction produces seizures and focal deficits (e.g. hemiplegia).

Diagnosis is suggested by venous (nonarterial territory) infarction and ‘empty delta’ sign (following contrast the wall of the sinus enhances but not the central thrombus on CT) and confirmed by occlusion of filling deficit on MR or CT venography. Outcome is variable; intracranial hypertension may develop (p. 378). A thorough search for causation – coagulation screen, drug history and underlying systemic illness – essential.

Treatment:

Correct causative factors (dehydration/infection etc)

Anticoagulation with heparin or alternative.

Deep cerebral venous thrombosis (10% of cases)

This produces venous infarction of the basal ganglion and other subcortical structures. Presentation with similar features; diagnosis can only be established by imaging (CT/MRI and MRV). Treatment as above.

Cavernous sinus thrombosis (5% of cases)

Commonly results from infection spreading from the jaw through draining veins or paranasal sinuses. Painful ophthalmoplegia, proptosis and chemosis with oedema of periorbital structures are associated with facial numbness and fever. The disorder may be bilateral. Base diagnosis on clinical suspicion supported by venography. Treatment with antibiotics and if indicated, sinus drainage.

CEREBROVASCULAR DISEASE – INTRACEREBRAL HAEMORRHAGE

By definition, ‘intracerebral haemorrhage’ occurs within the brain substance, but rupture through to the cortical surface may produce associated ‘subarachnoid’ bleeding. When the haemorrhage occurs deep in the hemisphere, rupture into the ventricular system is common.

CAUSES

In autopsy series, hypertension accounts for 40–50% of patients dying from non-traumatic haematomas. In hypertensive patients, degenerative changes weaken the walls of small intraparenchymal perforating vessels. Rupture usually occurs near a vessel bifurcation. The ‘microaneurysms’ originally described by Charcot and Bouchard are more likely to be small subadventitial haemorrhages or extravascular clots. In normotensive patients without any evident underlying pathology the cause remains unknown, but cryptic arteriovenous malformations are suspect especially in younger patients (i.e. less than 40 years) and when the haematoma is ‘lobar’ (i.e. frontal, temporal, parieto-occipital). In these patients, the haematoma may temporarily or permanently obliterate the lesion. Reinvestigation following haematoma resolution occasionally reveals previously undetected malformations. In the normotensive elderly patient, subcortical haematomas are commonly associated with amyloid vasculopathy, a degenerative disorder affecting the walls of arteries.

PATHOLOGICAL EFFECTS

Within 48 hours the blood and plasma act on surrounding brain causing disruption of the blood–brain barrier, vasogenic and cytotoxic oedema, neuronal damage and necrosis.

Haematoma resolution occurs in 4–8 weeks, leaving a cystic cavity.

INTRACEREBRAL HAEMORRHAGE

SITES

In hypertensive patients, up to 70% occur in the basal ganglia/thalamic region.

In normotensive patients:

CLINICAL EFFECTS

INVESTIGATIONS

A CT scan determines the exact site and size of the haematoma and excludes other pathologies.

Angiography/CT angiography

– Performed immediately if clinical state requires urgent operation, to identify a secondary cause i.e. arteriovenous malformation, aneurysm or vasculitis.

– Otherwise delayed until condition improves and the haematoma resolves, unless age and medical condition preclude further management.

In patients with negative angiography, a late MRI may demonstrate a CAVERNOUS ANGIOMA (see page 299).

MANAGEMENT	PROGNOSIS
For patients with intracerebral haemorrhage on anticoagulants, reverse using intravenous prothrombin concentrate and vitamin K. Supratentorial haematoma There is still no evidence to show that early evacuation of an intracerebral haematoma improves outcome.

Poor prognostic features

– Increasing age

– Large, deep lesions (basal ganglia/thalamic)

– Intraventricular blood

– Depth of conscious level (flexion or extension to painful stimuli).

In general, haematoma evacuation is indicated in patients who deteriorate gradually from the ‘mass’ effect, especially when the lesion lies superficially; operation will not benefit moribund patients, i.e. patients extending to painful stimuli with no pupil reaction. Good prognostic factors

– Small superficial lesions (i.e. frontal, temporal or parieto-occipital)

– Conscious patients or patients localising to painful stimuli.

The overall mortality ranges from 25–60% (90% if the patient is in coma) and is improved by an integrated ‘Stroke Unit’

Haemorrhage into the ventricles causes a sudden loss of consciousness. With a large bleed, death may follow from the pressure transmission from within the ventricular system. Blood in the ventricles does not in itself cause damage and, following clot resolution, complete recovery may occur.

No treatment is required; attempts at flushing out the ventricles usually fail. If the blood ‘cast’ causes obstructive hydrocephalus, then ventricular drainage (although hampered by the presence of blood) is indicated. Infusion of thrombolytic agents awaits evaluation.

SUBARACHNOID HAEMORRHAGE (SAH)

Intracranial vessels lie in the subarachnoid space and give off small perforating branches to the brain tissue. Bleeding from these vessels or from an associated aneurysm occurs primarily into this space. Some intracranial aneurysms are embedded within the brain tissue and their rupture causes intracerebral bleeding with or without subarachnoid haemorrhage.

Occasionally the arachnoid layer gives way and a subdural haematoma results.

Usually the headache is severe and the onset usually instantaneous (often described as a ‘blow to the head’). A transient or prolonged loss of consciousness or epileptic seizure may immediately follow. Nausea and vomiting commonly occur. Symptoms continue for many days.

Occasionally, the headache is mild (although still sudden onset) and may represent a ‘warning leak’ of blood before a major bleed.

Signs of meningism develop after 3–12 hours

Neck stiffness is present in most patients on passive neck flexion.

Kernig’s sign: stretching nerve roots by extending the knee causes pain.

Coma or depression of conscious level may result from the direct effect of the subarachnoid haemorrhage or from the mass effect of an associated intracerebral haematoma.

Focal damage from a haematoma will produce focal signs, e.g. limb weakness, dysphasia. The presence of a III nerve palsy indicates either transtentorial herniation or direct nerve damage from a posterior communicating artery aneurysm (or rarely from a basilar artery aneurysm).

Seizures frequently occur and may mask other features.

Fundus examination may reveal papilloedema or a subhyaloid or vitreous haemorrhage caused by the sudden rise in intracranial pressure.

A ‘reactive hypertension’ commonly develops, i.e. a rise in BP in patients with no evidence of pre-existing hypertension, and takes several days to return to normal levels.

Pyrexia is also a common finding; if severe and fluctuating, it may reflect ischaemic hypothalamic damage.

INVESTIGATIVE APPROACH

CT scan is the investigation of choice, perfomed as soon as possible after the headache onset. Lumbar puncture establishes the diagnosis of subarachnoid haemorrhage, but in patients with a mass lesion, lumbar puncture could precipitate transtentorial herniation.

Age limit for neurosurgical referral: Although mortality and morbidity increase with age, with the option of endovascular aneurysm treatment, age limitations no longer apply provided the patient’s clinical state is satisfactory.

CT scan

Confirms the diagnosis of SAH in 95% (if within 48 hours of the bleed).

Blood may be widely distributed

or more localised aiding identification of the site of the ruptured aneurysm

CT also identifies other associated lesions

– hydrocephalus

– intracerebral haematoma

– tumour

– arteriovenous malformation

MRI scan

Not routinely used, but in patients with multiple aneurysms, MRI performed several days after the bleed may provide greater sensitivity than CT in detecting small areas of subarachnoid clot and help determine the particular lesion responsible.

N.B. Spinal arteriovenous malformations can also cause SAH – if the patient’s pain begins in the back before spreading to the head, or if any features of cord compression exist, then MRI of the cervical or thoracic spine should be the preliminary investigation (see page 424).

CT/MR angiography

These non invasive techniques, particularly when combined with 3-D or 4-D imaging (colour as the 4th dimension), will detect up to 95% of intracranial aneurysms, but those < 3mm in diameter may be missed. Both MRA and in particular CTA can provide more information than conventional angiography about the aneurysm shape and size of the neck.

Demonstration of an aneurysm which matches the distribution of blood on standard CT, permits planning of treatment on the assumption that this is the source of the haemorrhage.

CT angiogram showing carotid aneurysm

Digital angiography

Four-vessel angiography is performed in patients with a negative CTA or MRA, in patients where further clarification of the vessels or the aneurysm is required to aid decision making or immediately prior to endovascular treatment.

With the latest equipment, 3-D rotational techniques are employed, combined with cropping of unwanted data, to permit the radiologist to focus on specific regions. Without this aid, antero-posterior, lateral and oblique views are required for each vessel.

Negative angiography

Angiography fails to reveal a source of the subarachnoid haemorrhage in approximately 20% of patients. In the presence of arterial spasm, reduction in flow may prevent the demonstration of an aneurysm and repeat angiography may be required at a later date.

Prognosis: In patients with a ‘perimesencephalic’ pattern of haemorrhage on CT scan and with negative angiography, the outlook is excellent; those patients with an ‘aneurysmal’ pattern with blood lying in the interhemispheric or Sylvian fissure still run a risk of rebleeding.

CEREBRAL ANEURYSMS

INCIDENCE

At autopsy intracranial aneurysms are found in approximately 2% of the population.

Aneurysm rupture occurs in 6–8 per 100 000 per year

Female:male = 3.2; but this ratio varies with age: < 40 years, male > females

> 40 years, females > males

Risk factors: atherosclerotic diseases (2.3x), family history (6x), polycystic kidney disease (4.4x).

Inheritance: investigations reveal aneurysms in 10% of relatives with two or more affected 1st degree family members. The genetic basis remains unknown. Procollagen III deficiency may play a role in some patients.

MORPHOLOGY

Intracranial aneurysms are usually saccular, occurring at vessel bifurcations. Size varies from a few millimetres to several centimetres. Those over 2.5 cm are termed ‘giant’ aneurysms.

Aneurysm rupture: usually occurs at the fundus of the aneurysm and the risk is related to size. Smoking, hypertension and alcohol excess also play a part. In some patients, rupture occurs during exertion, straining or coitus, but in most there is no associated relationship.

Since the severity of the haemorrhage relates to the patient’s clinical state and this in turn relates to outcome, much emphasis has been placed on categorising patients into 5 level grading systems, e.g. Hunt and Hess. A scale incorporating the Glasgow Coma scale (page 29) has been adopted by the World Federation of Neurosurgical Societies:

This grading scale correlates well with final outcome and provides a prognostic index for the clinician. In addition, it enables matching of patient groups before comparing the effects of different management techniques.

CEREBRAL ANEURYSMS – COMPLICATIONS

REBLEEDING

Rebleeding is a major problem following aneurysmal SAH. In the first 28 days (in untreated patients), approximately 30% of patients would rebleed; of these 70% die. In the following few months the risk gradually falls off but it never drops below 3.5% per year.

Adapted from Winn, Richardson, Jane 1977 Annals of Neurology

If, for example, a patient survives the first 30 days after a bleed, there is still a 20% chance of a rebleed occurring in the next 5 months. Even if patients survive the ‘high risk’ period in the first 6 months, there is still a considerable chance of rebleeding and death in the subsequent years.

The clinical picture of rebleeding is that of SAH, but usually the effects are more severe than the initial bleed. Most patients lose consciousness; the risk of death from a rebleed is more than twice that from the initial bleed.

Investigation

All patients deteriorating suddenly require a CT scan. This helps in establishing the diagnosis of rebleeding and excludes a remediable cause of the deterioration, e.g. acute hydrocephalus.

CEREBRAL ISCHAEMIA/INFARCTION

Following subarachnoid haemorrhage, patients are at risk of developing cerebral ischaemia or infarction and this is an important contributory factor to mortality and morbidity. Cerebral ischaemia/infarction may occur as an immediate and direct result of the haemorrhage, but more often develops 4–12 days after the onset, either before or after operation – hence the term ‘delayed cerebral ischaemia’. Approximately 25% of patients develop clinical evidence of delayed ischaemia/infarction; of these 25% die as a result. About 10% of the survivors remain permanently disabled.

Adapted from Vermeulen, Lindsay, Murray et al 1984 New England Journal of Medicine 311: 432–437

Aetiology of cerebral ischaemia/infarction

Several factors probably contribute to the development of cerebral ischaemia or infarction: ‘Vasospasm’: arterial narrowing on angiography occurs in up to 60% of patients after SAH and is either focal or diffuse. The development of ‘vasospasm’ shows a similar pattern of delay to that of cerebral ischaemia.

The angiogram appearance was initially thought to result from arterial constriction; this may be so, but the pathogenesis of ‘vasospasm’ now seems more complex. Many vasoconstrictive substances either released from the vessel wall or from the blood clot appear in the CSF after SAH, e.g. serotonin, prostaglandin, oxyhaemoglobin, endothelin-1 and endothelial synthesis of the vasodilator nitric oxide is reduced, but numerous studies with vasoconstrictor antagonists have failed to reverse the angiographic narrowing. This failure may be a result of the arteriopathic changes which have been observed in the vessel wall. Only calcium antagonists appear to have a beneficial effect (see page 291).

The greater the amount of blood in the basal cisterns (as shown on CT scan), the higher the incidence of arterial narrowing and associated ischaemic deficits.

Hypovolaemia

Hyponatraemia develops after SAH in many patients due to excessive renal secretion of sodium rather than a dilutional effect from inappropriate antidiuretic hormone secretion. Fluid loss and a fall in plasma volume lead to a raised blood viscosity with an increased risk of developing cerebral ischaemia.

Reduced cerebral perfusion pressure

Following SAH, intracranial haematoma or hydrocephalus may cause a rise in intracranial pressure (ICP). Since cerebral perfusion pressure = mean BP – ICP, a subsequent reduction in cerebral perfusion may occur.

Clinical effects of cerebral ischaemia/infarction

This may affect one particular arterial territory producing characteristic signs:

Commonly the ischaemia occurs in multiple areas, often in both hemispheres. This correlates with the pattern of arterial ‘spasm’.

Transcranial Doppler: a significant increase in flow velocity within an intracranial vessel may indicate developing ‘vasospasm’, even before clinical problems develop, and allow the early introduction of prophylactic measures (see page 291).

HYDROCEPHALUS

Following SAH, cerebrospinal fluid drainage may be impaired by:

Acute hydrocephalus occurs in about 20% of patients, usually in the first few days after the ictus; occasionally this is a late complication. In only one-third are symptoms of headache, impaired conscious level, dementia, incontinence, or gait ataxia severe enough to warrant treatment.

In a further 10% of patients, hydrocephalus develops late – months or even years after the haemorrhage.

Myocardial infarction/cardiac arrhythmias: electrocardiographic and pathological changes in the myocardium are occasionally evident after SAH, and ventricular fibrillation has been recorded. These problems are likely to occur secondarily to catecholamine release following ischaemic damage to the hypothalamus.

Pulmonary oedema: this occasionally occurs after SAH, probably as a result of massive sympathetic discharge; note the ‘pink, frothy’ sputum and typical auscultatory and chest X-ray findings.

Gastric haemorrhage: bleeding from gastric erosions occasionally occurs after SAH but rarely threatens life.

CEREBRAL ANEURYSMS – MANAGEMENT FOLLOWING SAH

Headache requires analgesia – codeine or dihydrocodeine. Stronger analgesics may depress conscious level and mask neurological deterioration. Management is otherwise aimed at preventing complications –

PREVENTION OF REBLEEDING

Bed rest: Often enforced after SAH, although there is no evidence that this reduces the rebleed risk. Allowing gentle mobilisation and using the toilet may induce less ‘stress’ than using a bedpan.

Aneurysm repair: Both surgical (clipping of the aneurysm neck) and endovascular (coil embolisation of the aneurysm sac) techniques are used. Aneurysm repair, whether coiling or clipping, is performed within 48 hours of the bleed, but this is not always feasible. Operative risks are greater the earlier the procedure, but the greater the delay, the greater the risk of rebleeding. Despite this, in past years operation was often deferred in patients in poor clinical condition. Endovascular techniques appear to be less dependent on timing and avoid potentially harmful effects of brain retraction and vessel dissection. This supports their use in the elderly or in patients in poor clinical condition, but other factors must also be considered – see page 290. Once the aneurysm is clipped, aggressive methods of treating ischaemia with induced hypertension can be applied – see page 291.

OPERATIVE TECHNIQUES

Direct clipping of the aneurysm neck: Through a craniotomy and using the operating microscope, the surgeon dissects out the aneurysm and applies a clip across the neck without compromising the proximal or distal vessels. Clipping prevents rebleeding; clip slippage rarely occurs. If any part of the neck lies outwith the clip, this may occasionally lead to recurrent growth.

Wrapping: If the width of the aneurysm neck or its involvement with adjacent vessels prevents clipping, then muslin gauze may be wrapped around the fundus. This provides some protection, but rebleeding may still occur.

Trapping: Used for giant aneurysms (>25mm diameter) where other methods have failed due to the width of the aneurysm neck. Should be combined with cerebral revascularisation to minimize the risk of ischaemia. Techniques include either superficial temporal–middle cerebral artery anastomosis or insertion of a saphenous vein or radial artery bypass graft from the carotid to the middle cerebral artery.

ENDOVASCULAR TECHNIQUES

Coil embolisation: this endovascular technique, where multiple helical platinum coils are packed into the aneurysm fundus, has been developed and refined over the last two decades. A tracker catheter is inserted via a femoral puncture and guided up through the arterial system into the aneurysm sac.

Posterior communicating aneurysm before and after coil embolisation

The coil attached to the end of a delivery wire is then guided into the fundus and after accurate placement, the passage of an electric current causes electrochemical release. On average, 4–5 coils are required to pack each aneurysm.

The radiologist aims to completely obliterate the fundus, but this is not always feasible and to avoid occluding the adjacent vessel, a portion of the neck may remain. In either case, a small risk of rebleeding persists, even when completely obliterated. Thrombotic complications may also occur during the procedure.

Balloon remodelling: the wider the aneurysm neck, the greater the risk that coils will project into and occlude the vessel lumen. A balloon is attached to a second catheter and periodically inflated across the aneurysm neck during coil insertion to preserve the vessel lumen.

Basilar bifurcation aneurysm with wide neck –

Stent assisted coil embolisation: for very wide-necked aneurysms or for those where balloon remodelling has failed, one or more stents can be manouvred through the parent vessel alongside the aneurysm neck. Coils are then packed into the fundus via a tracker catheter passed through the interstices of the stent. Such patients require long-term anti-platelet therapy to prevent thrombotic complications and this may create difficulties in the acute phase of SAH management.

Balloon occlusion: On rare occasions the above operative or endovascular techniques fail to treat ‘giant’ or fusiform aneurysms arising from the carotid artery. Temporary balloon occlusion of the carotid artery for a 30 minute period tests whether the patient’s collateral circulation from the Circle of Willis is sufficient to sustain flow through the hemisphere. Similarly temporary occlusion of the vertebro-basilar system is possible. If tolerated, intra-arterial inflation of a detachable balloon can provide permanent occlusion. Intra-arterial balloon inflation can also provide temporary intra-operative protection when proximal control is difficult to achieve.

Wide necked basilar aneurysm with one stent inserted into the left posterio rcerebral artery, and another stent passing through the interstices of the first and inserted into the right posterior cerebral artery. Coils will be passed beyond the stent into the aneurysm fundus.

SELECTION OF TREATMENT

Until recent years direct surgical clipping was the standard method of aneurysm treatment. Coil embolisation was reserved for aneurysms technically difficult to repair, particularly those in the posterior circulation. A large multicentre randomized trial of clipping vs. endovascular treatment (the International Subarachnoid Aneurysm Trial – ISAT) demonstrated a 23% reduction in the proportion of patients with a poor outcome (dependent or dead) at one year in those patients undergoing coil embolisation, despite more rebleeds occurring in this group. Following publication in 2002, the proportion of patients undergoing coil embolisation as the first line of treatment dramatically increased, reaching 85–90% in some centres. This swing occurred despite the trial being weighted towards small anterior circulation aneurysms in patients in good clinical condition. Concern persisted that coil treatment would not eliminate rebleeding. Long-term follow up (mean 9 years after treatment) of the trial patients has shown that although rebleeding was higher in the coil treatment group, the risk of death was still significantly lower in coiled patients. In young patients e.g. 30–40 years of age, with 40 years of expectant life, the rebleeding concern after coil treatment persists and clipping may be the preferred option.

Aneurysm treatment requires a team approach involving interventional radiologists and neursurgeons. Treatment selection must take a variety of factors into account including the nature and location of the aneurysm, the relative difficulties of the endovascular or operative approach and the patients age and clinical condition. Some patients e.g. those with basilar, carotid and anterior cerebral aneurysms, the elderly or those in poor clinical condition are more likely to require coil embolisation, whereas others, such as those with large middle cerebral aneurysms are more likely to require direct operative treatment. Unfortunately aneurysms that are difficult to treat with one technique are often difficult to treat with both methods. Patients undergoing coil treatment require check angiography/CT angiography follow-up, e.g. 6 months and 2 years, to ensure recanalisation has not occurred. Up to 10% will require retreatment.

PREVENTION OF CEREBRAL ISCHAEMIA/INFARCTION

Despite considerable clinical and experimental research, cerebral ischaemia is still a major cause of morbidity and mortality after subarachnoid haemorrhage. In recent years some advances have proved beneficial.

Calcium antagonists: several large studies and a meta-analysis have confirmed that Nimodipine reduces the incidence of cerebral infarction by about one third and improves outcome. Whether this acts by improving collateral circulation, by reducing the harmful effect of calcium flooding into brain cells or by reducing cerebral ‘vasospasm’ remains uncertain.

Avoidance of antihypertensive therapy: after SAH, autoregulation (page 79) is often impaired; a drop in BP causes a reduction in cerebral blood flow with a subsequent risk of cerebral ischaemia. Patients on long-term antihypertensive treatment can continue with this therapy, but ‘reactive’ hypertension should not be treated.

High fluid intake (haemodilution): maintenance of a high fluid input (3 litres per day) may help prevent a fall in plasma volume from sodium and fluid loss. If hyponatraemia develops do not restrict fluids (this significantly increases the risk of cerebral infarction). If sodium levels fall below 130 mmol/1, give hypertonic saline or fludrocortisone.

Plasma volume expansion (hypervolaemia): expanding the plasma volume with colloid, e.g. plasma proteins, dextran 70, Haemacel, increases blood pressure and improves cerebral blood flow. This should be given either prophylactically in high risk patients (heavy cisternal blood load on CT scan or with high Doppler velocities) or at the first clinical sign of ischaemia. If clinical evidence of ischaemia develops despite this treatment, then (if the aneurysm has been repaired) combine with:

Hypertensive therapy: treatment with inotropic agents, e.g. dobutamine, increases cardiac output and blood pressure. Since cerebral autoregulation commonly fails after subarachnoid haemorrhage, increasing blood pressure increases cerebral blood flow. Up to 70% of ischaemic neurological deficits developing after aneurysm operations can be reversed by inducing hypertension; often a critical level of blood pressure is evident.

Early recognition and treatment of a developing neurological deficit may prevent progression from ischaemia to infarction. Delayed treatment may merely aggravate vasogenic oedema in an ischaemic area. This technique of induced hypertension is now widely applied, with good results, but requires careful, intensive monitoring. In view of the risk of precipitating aneurysm rupture, it is reserved until after aneurysm repair.

Transluminal angioplasty/papaverine infusion: this involves balloon dilatation of the vasospastic segment of the vessel. It is usually combined with an intra-arterial infusion of the antispasmodic agent papaverine. Although no controlled studies exist, many small studies report a beneficial effect on cerebral blood flow and on clinical state. Timing is difficult. If used too early, the patient may be unnecessarily exposed to an invasive procedure; if too late, the ischaemia may be irreversible. Consider angiography and angioplasty if other measures (haemodilution/hypervolaemia/hypertension) have failed to reverse a significant clinical deterioration within a few hours.

Brain protective agents: to date, studies of neuroprotective drugs (antioxidants and anti-inflammatory agents) other than calcium antagonists, have failed to demonstrate a beneficial effect. Some recent studies assessing magnesium sulphate infusion, pravastatin and the endothelin-1 antagonist clazosentan have had encouraging results, but await further evaluation.

Antifibrinolytic agents: i.e.tranexamic acid, epsilon aminocaproic acid should not be used.

These agents prevent rebleeding by delaying clot dissolution around the aneurysm fundus, but any beneficial effect is offset by an increased incidence of cerebral ischaemia.

HYDROCEPHALUS

Hydrocephalus causing acute deterioration in conscious level requires urgent CSF drainage with a ventricular catheter (in ‘communicating’ hydrocephalus a lumbar drain provides an alternative. Lumbar puncture may provide temporary benefit).

Gradual deterioration or failure to improve in the presence of enlarged ventricles indicates the need for permanent CSF drainage with either a ventriculoperitoneal or lumboperitoneal shunt.

EXPANDING INTRACEREBRAL HAEMATOMA

Intracerebral haematomas from ruptured aneurysms do not require specific treatment unless the ‘mass’ effect causes a deterioration of conscious level. This necessitates urgent CT or digital angiography followed by evacuation of the haematoma with or without simultaneous clipping of the aneurysm; under these circumstances, operative mortality is high.

OUTCOME AFTER SUBARACHNOID HAEMORRHAGE

The National Study of Subarachnoid Haemorrhage collected information on patients admitted to all neurosurgical units in the UK and Ireland between September 2001 and September 2002 and provides useful information on outcome. The study included 3174 patients, of which 2397 had a confirmed aneurysm. (Published by the Royal College of Surgeons, 2006 – available online)

Of those patients surviving the initial bleed and admitted to the neurosurgical unit with a confirmed aneurysm, 11% died in hospital. Of those undergoing aneurysm repair, 40% made a good recovery; a further 21% had moderate disability and were independent.

Factors associated with unfavourable outcome were: age, clinical condition on admission, quantity of subarachnoid blood on CT scan and the presence of pre-existing medical illness.

Table showing relationship of admission grade to outcome

Neurological grade on admission (WFNS)	No. of patients undergoing aneurysm repair	Unfavourable outcome – death/severe disability (percentage)
I	1214	24.7
II	378	37.6
III	88	48.9
IV	164	64.0
V	118	71.2

Of all patients with a confirmed aneurysm, 92% underwent repair, 53% by surgical clipping and 38% by coil embolisation. No difference was noted in outcome between the two groups even after case mix adjustment (unfavourable outcome 35% for clipped group: 34% for coiled group).

Comparing different operative or management policies: Comparison of different treatments for ruptured aneurysms is difficult, unless conducted under the confines of a randomised controlled trial. ‘Operative mortality’ provides limited information unless patient groups are carefully matched for age, clinical condition and timing of operation. ‘Management mortality’ (e.g. outcome of all admitted patients up to 3 months from the ictus) is of more practical value, but even then, admission policies require careful scrutiny.

CEREBRAL ANEURYSMS – UNRUPTURED

UNRUPTURED ANEURYSMS

Identification of unruptured aneurysms may result from –

– Investigation of unrelated neurological symptoms with CT, MRI or angiography

– Investigation of symptoms arising as a result of aneurysmal compression of adjacent structures

– Investigation of patients with a family history of aneurysmal SAH (see page 295)

– Investigation of SAH when multiple aneurysms exist (about 25% of patients)

Management: depends on the above circumstances and on balancing the risk of rupture (and death) in future years against the risk of aneurysm repair; the decision is often difficult. The International Study of Unruptured Intracranial Aneurysms (ISUIA), by far the largest study of its kind, examined both the natural history and the results of treatment of unruptured aneurysms. The data suggested that the risk of rupture related to the size, site and the occurrence of a SAH from a previously treated source. For small aneurysms < 7 mm in diameter and no previous SAH, the annual risk of rupture was 0.1% (far lower than the 1–2% suggested from previous smaller studies). For aneurysms > 12 mm in diameter the annual risk of rupture ranged from from 3–10% depending on the site and size. For those treated, the study also reported a combined mortality and morbidity of from 7–10% for the coiled patients and from 10–13% for the operated patients, a figure higher than surgeons had previously liked to admit. The operative risk increased with age, aneurysm size and a site on the posterior circulation.

When determining appropriate management, the following factors must be taken into account

– patient’s age, life expectancy and the occurence of a previous haemorrhage

– aneurysm size and site

– the possibility of future growth (about 1/3 expand > 3 mm over 20 years)

– the patient’s view (a conservative approach can create considerable stress)

– the operative/endovascular results of unruptured aneurysm treatment for that centre

In general treatment would not be recommended for anterior circulation aneurysms < 7 mm in size and without a previous SAH, although this view may change with continued improvement in endovascular techniques.

For those undergoing a conservative approach, it is essential to ensure that they do not smoke, since this doubles the risk of aneurysm rupture.

When aneurysms present with compressive symptoms such as a III nerve palsy, it is assumed that recent expansion has occurred and that rupture could be imminent. Such patients normally receive urgent treatment.

Cumulative 5 year rupture rates for unruptured aneurysms at different sites (ISUIA, Lancet 2003)

CEREBRAL ANEURYSMS – SCREENING

SCREENING FOR INTRACRANIAL ANEURYSMS

When two or more first-degree relatives have a history of cerebral aneurysms or SAH, then other members of that family (over the age of 25 years) have an increased risk of harbouring an intracranial aneurysm (about 10% or 6x greater than the rest of the population). A similar increased risk occurs for patients with a genetic predisposition, e.g. polycystic kidney disease, Type IV Ehlers-Danlos. Before undergoing screening to detect whether such an aneurysm exists, several important facts should be considered –

– We do not know how rapidly aneurysms form. They may develop over a few hours, days or weeks. A negative screening investigation will fail to provide the reassurance that a subarachnoid haemorrhage from a ruptured aneurysm will never occur.

– The ISUIA study described above, suggests that for small aneurysms (< 7 mm), the rupture risk is extremely low. Even if a small aneurysm is found, treatment risks may preclude any action.

– Aneurysm repair, either by direct operation or by coil embolisation, carries a risk of death or disability, which depends on the patient’s age and the size and site of the aneurysm.

– The presence of an aneurysm may carry implications for life insurance, mortgage applications and even for future pregnancies (since the risk of aneurysm rupture is increased during pregnancy).

– It is impractical to consider screening in relatives < 20–25 years (due to the rarity of aneurysms in this age group) and in those > 60–70 years since the risks outweigh any potential benefit.

– In those with only one affected first-degree relative the low, albeit slightly increased risk of finding an unruptured aneurysm, is still insufficient to justify screening.

If after consultation and consideration of these issues the patient wishes to proceed with screening, then CT angiography would be the most appropriate technique, accepting that this may fail to detect aneurysms 3 mm or less in diameter. For those who decide not to undergo screening, other measures may minimise the risk of aneurysm formation in the future – avoid smoking and treat elevated blood pressure and cholesterol.

After a negative investigation, the patient may wish to consider the possibility of a further screen in 3–5 years time.

VASCULAR MALFORMATIONS

Vascular malformations vary in size and different forms exist:

Arteriovenous malformations (AVMs) are developmental anomalies of the intracranial vasculature; they are not neoplastic despite their tendency to expand with time and the descriptive term ‘angioma’ occasionally applied.

Dilated arteries feed directly into a tangled mass of blood vessels of varying calibre; they bypass capillaries and shunt oxygenated blood directly into the venous system. Due to high intraluminal pressure, veins may adopt an ‘aneurysmal’ appearance. Arteriovenous malformations occur at any site but are commonest in the middle cerebral artery territory.

Capillary telangiectasis: an area of dilated capillaries, like a small petechial patch on the brain surface – especially in the pons. These lesions are often only revealed at autopsy.

Cavernous malformation/angioma: plum coloured sponge-like mass composed of a collection of blood filled spaces with no intervening brain tissue. No enlargement of feeding or draining vessels.

About 40–60% of patients with an AVM present with haemorrhage – often with an intracerebral or intraventricular component. In comparison with saccular aneurysms, AVMs tend to bleed in younger patients, i.e. 20–40 years, and are less likely to have a fatal outcome. Vasospasm and delayed ischaemic complications rarely develop. Small AVMs, those with high intranidal pressure and those draining exclusively to deep veins have an increased risk of haemorrhage.

Annual risk of haemorrhage: patients with no history of haemorrhage have an annual risk of bleeding of 2–4%. For those presenting with haemorrhage, the risk of rebleeding may be higher, particularly in the first year. One study reported an annual risk of 17%.

Mortality from haemorrhage: in contrast to the high mortality following aneurysm rupture, haemorrhage from an AVM carries the relatively low mortality rate of approximately 10%.

Epilepsy

Generalised or partial seizures commonly occur in patients with arteriovenous malformation, especially if the lesion involves the cortical surface. Of patients presenting with haemorrhage, 30% have a history of epilepsy.

Neurological deficit

Large AVMs, especially those involving the basal ganglia, may present with a slowly progressive dementia, hemiparesis or visual field defect, probably as a result of a ‘steal’ effect. The infrequent brain stem AVM may also produce a motor or sensory deficit, with or without cranial nerve involvement.

Both CT and MR angiography should confirm the presence of an AVM but digital subtraction four-vessel angiography is required to delineate the feeding and draining vessels. Occasionally small AVMs are difficult to detect and only early venous filling may draw attention to their presence.

N.B. In the presence of a haematoma, digital subtraction angiography should be delayed until the haematoma resolves, otherwise local pressure may mask demonstration of an AVM. If the angiogram is subsequently negative, then MRI is required to exclude the presence of a cavernous malformation.

MANAGEMENT

Various methods of treating arteriovenous malformations are available. All risk further damage and a team comprised of the neurosurgeon and neuroradiologist should decide on the optimal method or combination of methods for each patient. The urgency of the patient’s clinical condition and the risks of treatment must be weighed against the risk of a conservative approach. The Spetzler-Martin grading system provides a useful guide to operative risk.

Methods of treatment

Operation:	Excision – complete excision of the AVM (confirmed by per-or postoperative angiography) is the most effective method of treatment particularly for small AVMs in non-eloquent areas. Image guidance (page 386) may aid localisation.
	Larger lesions (> 6 cm) have a greater risk of postoperative hyperperfusion syndrome and brain swelling and carry a 40% risk of permanent neurological deficit.
Stereotactic
radiosurgery:	Focused beams from multiple cobalt sources or from a linear accelerator (25Gy) obliterates about 75% of AVMs < 3 cm in diameter, but this may take up to 3 years during which time the risk of haemorrhage persists. In smaller lesions < 1 cm the obliteration rate with 25 Gy approaches 100%. For lesions greater than 3 cm, the lower dose required to minimise the damaging effect of local tissue destruction, makes obliteration unlikely. Pre-treatment with embolisation helps only if this produces a segmental reduction in size. Suboptimal embolisation may merely hinder radiosurgical treatment. Despite the delay in action, radiosurgery may prove ideal for small deeply seated lesions.
Embolisation:	Skilled catheterisation permits selective embolisation of feeding vessels with isobutyl-cyanoacrylate, although this technique is not without risk.
	Embolisation may cure up to 40% of AVMs when small particularly if supplied by a single feeding vessel, but filling may persist from collaterals. When used preoperatively, it may significantly aid operative removal.

CAVERNOUS MALFORMATIONS (syn. cavernous angioma, cavernoma)

Cavernous malformations occur in 0.5% of the population. They are occasionally multiple and in a few patients, have a familial basis. A cavernous malformation may present with epilepsy, haemorrhage or with focal neurological signs. MRI is the investigation of choice as cavernous malformations, are often missed on CT scanning and rarely seen on angiography. Most lesions show marked signal change around this lesion due to a rim of haemosiderin deposition.

The annual risk of haemorrhage is about 1% per year, but this varies depending on whether the lesion lies deeply (i.e. brain stem or basal ganglia) or superficially. With deep lesions in critical sites, a small bleed causes damage more readily. For deep lesions the risk of a bleed sufficiently severe to cause neurological signs is about 5% per year, whereas for superficial lesions, this is almost zero. Unfortunately the high risk, deep lesions are more hazardous to surgically remove, although this may be the appropriate management in selected patients.

VEIN OF GALEN MALFORMATION

The term ‘vein of Galen’ malformation is actually a misnomer since this is a type of arteriovenous malformation in which arteries feed directly into the embryonic precurser of the great vein of Galen (the prosencephalic vein of Markowski) causing massive aneurysmal dilatation. Patients present either in the neonatal period with severe high output cardiac failure due to the associated arteriovenous shunt, in infancy with cranial enlargement due to an obstructive hydrocephalus, or in childhood with subarachnoid haemorrhage. A cranial bruit is always evident. Cardiac failure usually develops in the neonatal period and is usually fatal. In the other groups the treatment of choice is now endovascular obliteration of the feeding vessels followed by ventricular drainage if required. As a result, the high mortality and morbidity experienced with direct operative repair has been considerably reduced.

STURGE-WEBER SYNDROME

Angiomatosis affecting the facial skin, eyes and leptomeninges produces the characteristic features of the Sturge-Weber syndrome – a capillary naevus over the forehead and eye, epilepsy and intracranial calcification. (See page 563.)

DURAL ARTERIOVENOUS FISTULA

In contrast to AVMs these fistulous communications are usually acquired rather than developmental in origin. Arterial blood drains directly into either a venous sinus, cortical veins or a combination of both (see carotid-cavernous fistula page 301). The aetiology remains unknown, but sinus thrombosis or trauma may play a part. In a benign form, no reversal of flow occurs and no treatment is required. When retrograde venous flow occurs, venous hypertension results and haemorrhage may follow. For this type, treatment requires ligation and division of the draining vein, often combined with endovascular occlusion.