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Spontaneous intracranial haemorrhage
Neurosurgery
Spontaneous intracranial haemorrhage
Sites and causes of intracranial haemorrhage
Joan P Grieve
Extradural
Almost exclusively traumatic
Subdural
Trauma (may be minor) Anticoagulation/Clotting disorders Aneurysm (rarely) Secondary to subarachnoid or intraparenchymal haemorrhage Trauma Aneurysms Hypertension Anticoagulants Amyloid angiopathy Arteriovenous malformations Aneurysms Cavernous angiomas Amphetamine/cocaine ingestion Infective endocarditis Tumours Disseminated intravascular coagulation Venous thrombosis Cerebral vasculitis Trauma Anticoagulants Secondary to subarachnoid or intraparenchymal haemorrhage Subependymal vascular malformation
Subarachnoid
Abstract
Intracerebral
Intracranial haemorrhage, the pathological accumulation of blood within the cranial vault, may occur within brain parenchyma or the surrounding meningeal spaces and is most commonly caused by trauma. Spontaneous intracranial haemorrhage generally occurs within the subarachnoid (SAH), intracerebral (ICH) and intraventricular (IVH) spaces. SAH usually occurs as a result of aneurysmal rupture and happens with an annual incidence of 10/100 000 population. Non-traumatic ICH accounts for 8–13% of all strokes and results from a wide spectrum of disorders. However it most commonly results from hypertensive damage to blood vessel walls (e.g., hypertension, eclampsia, drug abuse). ICH is more likely to result in death or major disability than ischaemic stroke or SAH. Symptoms vary depending on the location of the bleed and the amount of brain tissue affected. The symptoms usually develop suddenly and without warning, although they may occasionally develop in a stepwise, episodic manner or they may get progressively worse, either as a result of further haemorrhage (a particular risk in aneurysmal SAH) or the development of oedema surrounding a focal haematoma. The presence of blood within the ventricular system also predisposes the patient to deterioration from secondary hydrocephalus. This may be of acute onset but may also develop much more insidiously. Management is generally supportive. The identification of any underlying structural vascular abnormality, particularly when an intracranial aneurysm is suspected, is important, allowing early treatment and the prevention of rehaemorrhage.
Intraventricular
Table 1
Subarachnoid haemorrhage A subarachnoid haemorrhage (SAH) involves the accumulation of blood between the arachnoid and the pia mater. The main cause of non-traumatic SAH is rupture of an intracranial aneurysm, which accounts for 85% of cases. It is a devastating condition with an overall case fatality of 50% (including pre hospital deaths), with 30% of survivors being left dependent because of major neurological deficits. Five percent of cases are caused by rare conditions, including arteriovenous malformations (including spinal AVMs), cerebral vasculitides, tumours, dural arteriovenous fistula, dural sinus thrombosis, carotid or vertebral artery dissections, coagulopathy and drugs. The remaining 10% of patients will have no obvious cause for their haemorrhage and a normal angiogram. The annual incidence of aneurysmal SAH is approximately 10 per 100 000, increasing to a peak incidence at 55–60 years. There is a female preponderance, with reported male-to-female ratios of 1:1.8. Most cases of aneurysmal SAH are sporadic; however there is considerable evidence to support the role of genetic factors in the development of intracranial aneurysms. There is a strong association between intracranial aneurysms and heritable connective tissues diseases, such as autosomal dominant polycystic kidney disease, Marfan’s syndrome, pseudoxanthoma elasticum, Ehlers-Danlos syndrome and alpha-1 antitrypsin deficiency.
Keywords intracerebral haemorrhage; intraventricular haemorrhage; spontaneous intracranial haemorrhage; subarachnoid haemorrhage
Introduction Intracranial haemorrhage may be classified according to location (Table 1), the commonest cause of all intracranial haemorrhage being trauma. Spontaneous intracranial haemorrhage (without accompanying trauma) however most commonly occurs in the form of subarachnoid haemorrhage, intracerebral haemorrhage and intraventricular haemorrhage. Rarely a subdural haematoma can develop when a subarachnoid or intraparenchymal bleed extends into the subdural space through a tear in the arachnoid.
Joan P Grieve MD FRCS(SN) is a Consultant Neurosurgeon at The National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
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Most aneurysms arise from the anterior circulation with 85–95% from the internal carotid artery (ICA) system and 5–15% the posterior circulation. Anterior communicating artery aneurysms are the commonest lesion, particularly in men (46.1% in men versus 26.6% in women). Also common are aneurysms arising from the ICA, especially in women (36.8% compared with 18% of men). Posterior communicating artery aneurysms are found in 20–25% of individuals whilst middle cerebral artery aneurysms are found in 15–20%. Within the posterior circulation, 10% arise from the basilar artery, the basilar tip being the most common site, followed by superior cerebellar junction and 5% arise from the vertebral artery, posterior inferior cerebellar artery being the most common site. Ten to 15% of cases will have a normal angiogram. Of these, 65% will have a distinctive pattern of subarachnoid blood lying in the prepontine or perimesencephalic cisterns. These patients tend to be younger, non-hypertensive, of better clinical grade and more often male than SAH patients with positive angiograms. The aetiology of these cases is unclear but may be due to venous haemorrhage. The overall prognosis tends to be good, partly because rebleeding is rare and few patients develop delayed ischaemic deficit. However the diagnosis should only be entertained with caution as 10% of vertebrobasilar aneurysms present with a similar distribution of blood.
In addition, familial intracranial aneurysms account for 7–20% of patients. Environmental factors have been extensively studied and cigarette smoking is the only factor consistently identified raising the risk 3–10 times. Hypertension is also almost certainly important but to a lesser degree. It seems that hypertension and smoking act as synergistic risk factors. The use of sympathomimetic drugs, such as cocaine and metamphetamine, tend to increase the incidence and decrease the age at which aneurysmal rupture occurs; aneurysmal size at rupture also tends to be smaller. Clinical features The cardinal clinical feature is of a “thunderclap headache”. Headache is present in up to 97% of patients and is often accompanied by nausea and vomiting (77%). Consciousness is frequently altered, with confusion and lethargy in 30%, transient loss of consciousness in one third and coma in 17%. Neurological abnormalities are seen in 64% of cases with focal signs such as hemiparesis, IIIrd or VIth nerve palsies in 21%. Focal deficits may be caused by intraparenchymal haemorrhage. A painful pupil-involving IIIrd nerve palsy without headache is usually taken as imminent rupture of a posterior communicating artery aneurysm and should therefore be dealt with promptly. Investigation CT scanning is mandatory in those with suspected SAH, generally revealing diffuse blood of a symmetrical distribution around the basal cisterns, sylvian fissures and cortical sulci. Modern generation CT will demonstrate the presence of blood in 98% of patients scanned within 48 hours. However blood is rapidly cleared from the CSF and the sensitivity gradually decreases. Head CT scanning can also demonstrate secondary hydrocephalus, cerebral ischaemia or infarction, mid-line shift or re-haemorrhage. If clinical suspicion is strong and the CT is normal, lumbar puncture, preferably by an experienced operator, should be performed. If clinically appropriate this should be delayed for 12 hours from the ictus to allow time for xanthochromia (yellow discolouration) to develop. Xanthochromia of the supernatant is diagnostic of SAH. This must be determined by spectrophotometry rather than visual inspection. Negative CSF is very helpful in excluding SAH but bloodstained CSF may result from a traumatic tap. A decrease in the number of red cells from bottle one to three is a very unreliable way of differentiating SAH from a traumatic tap. It should be remembered that patients may have had both SAH and a traumatic tap. Conventional MRI is not sensitive to acute haemorrhage as there is too little methaemoglobin for haemorrhage to be easily differentiated from CSF. Visualisation of blood on MRI is, however, better after 4–7 days and is therefore excellent at demonstrating subacute to remote SAH, when CT sensitivity decreases. In patients with either equivocal or diagnostic CT/lumbar puncture, some form of structural imaging is undertaken to identify the ruptured aneurysm. Digital subtraction angiography (DSA) has been the gold standard investigation until recently, but advances in three-dimensional CT angiography have meant that it now has a sensitivity and specificity approaching that of DSA (sensitivity of 77–97% and specificity of 87–100%). Its non-invasive nature may ultimately obviate the need for cerebral angiography with its inherent risks, at least as a first line investigation.
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Initial management General supportive care should be instituted. Stabilisation of the patient, with optimisation for aneurysm treatment, together with prevention of secondary cerebral insults is achieved by ensuring adequate ventilation and oxygenation, normovolaemia and haemodynamic stability and control of intracranial pressure. Frequent neurological examination is required in order to identify any neurological deterioration requiring further investigation or management. Bed rest is generally recommended until aneurysm treatment is undertaken. Nimodipine, a calcium channel antagonist, has been shown to reduce the risk of cerebral infarction due to vasospasm by 34% and, as a result, poor outcome following SAH by 40%.1 A dose of 60 mg 4-hourly either orally or via a nasogastric tube is used. With an unsecured aneurysm, gentle volume expansion with slight haemodilution may help to return the circulating volume to normal and prevent or minimise the effects of vasospasm; however hypertension should be avoided. Once the aneurysm is secured, hypertension is allowed, but there is no agreement on the range. Analgesia is often required. Aneurysmal treatment Currently the two main treatment options for securing of an aneurysm are neurosurgical clipping and endovascular coiling. Traditionally craniotomy and clipping of the aneurysm has been the preferred method, although the timing of surgery has been debated. The rebleeding rate from aneurysms is particularly high in the first two weeks and then declines. This early high rebleed rate, which may have devastating complications, together with more recent improvements in microsurgical techniques is the reason why early intervention is generally favoured. Securing the aneurysm will also facilitate the treatment of complications such as cerebral vasospasm. 121
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Neurosurgery
(low-intravascular volume) or syndrome of inappropriate anti-diuretic hormone (SIADH) (normal or increased intravascular volume), if left untreated has a high associated morbidity and mortality. Their distinction is important as cerebral salt-wasting is treated by aggressive fluid administration and sodium supplements, whilst treatment of SIADH involves fluid restriction. Fluid restriction of patients with cerebral salt wasting will worsen their hypovolaemia and will therefore predispose them to vasospasm.
The Guglielmi Detachable Coil (GDC) has been available since 1991 and has been increasingly used in clinical practice. Detachable platinum coils are delivered endovascularly into the aneurysm. Once the correct position within the aneurysm has been achieved, the coil is detached from this wire. Multiple coils of various lengths and thicknesses are often packed into the aneurysm to exclude it from the circulation. The results of the International Subarachnoid Aneurysm Trial (ISAT) suggest that 23.5% of patients treated by endovascular means were dead or dependent at 1 year, compared with 30.9% allocated to neurosurgery, an absolute risk reduction of 7.4%.2 The early survival advantage is maintained for up to 7 years and was significant despite a higher late rebleeding rate. However, many aneurysms are not equally suitable for either microsurgical clipping or endovascular coiling. In individual cases, several factors – such as patient’s age and overall medical condition and the aneurysm’s location, size, morphology and relationship to adjacent vessels – need to be analysed in the context of a multidisciplinary team to decide on the most appropriate treatment.
Outcome Pre-hospital mortality is 3–26%, with an overall mortality of 45–60% in the first 30 days after SAH. Overall morbidity is quoted as 25–33%, caused in the majority of patients by vasospasm, although initial deficits and intervention also contribute. The major predictive factors for a poor outcome are level of consciousness on admission, age and amount of blood on presenting CT. More than 50% of survivors report problems with memory, mood or neuropsychological function. Despite this half to two thirds of survivors are able to return to work one year after presentation.
Complications If unprotected, 15–20% of patients will rebleed in the first 2 weeks, carrying with it a significant mortality (50–75%) and risk of permanent neurological disability. There appears to be an initial peak of rehaemorrhage in the first 48 hours of approximately 4%, which rapidly plateaus to 1–2% per day until 40 days post-haemorrhage. After 6 months there is a long-term risk of further haemorrhage of 3% per year. The risk of rebleed is increased with poor clinical grade, posterior circulation lesions, hypertension, elderly patients and abnormal haemostatic parameters. Symptomatic vasospasm (synonymous with delayed ischaemic deficit) occurs in 20–30% of patients and is at its worst 3–14 days following the haemorrhage. The mechanism by which vasospasm is effected is poorly understood. A multifactorial origin is most probable with the liberation of spasmogenic metabolites during clot lysis in the basal cisterns and the impairment of cerebral vasodilatation related to endothelial dysfunction and structural changes in the arterial wall. Following SAH there appears to be an imbalance between the vasodilating and vasoconstricting influences that are normally present. If severe, vasospasm can lead to cerebral infarction. The severity and distribution of vasospasm are related to the amount and site of subarachnoid blood. Diagnosis can be difficult and is often made after exclusion of other causes of neurological deterioration such as hydrocephalus, electrolyte disturbance, seizures or a rebleed. Once identified, patients are treated with hypervolaemia and induced hypertension. In those patients refractory to medical treatment, transluminal angioplasty or vasodilator infusion (for example papaverine or nifedipine) can be used to improve both angiographic appearances and the patient’s clinical condition. Symptomatic hydrocephalus is seen in 10–35% of patients. This may be either obstructive, caused by an intraventricular clot, or communicating, caused when the subarachnoid blood blocks CSF reabsorption through the arachnoid villi. Acutely it is treated by a period of external ventricular drainage but in the longer term, 10–15% of patients will require placement of a permanent ventriculo-peritoneal shunt. Electrolyte disturbances, most commonly of sodium, are seen in 28%. Hyponatraemia, caused by cerebral salt-wasting
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Intracerebral haemorrhage Spontaneous intracerebral haemorrhage (ICH) results from intracerebral arterial rupture, particularly of perforating vessels, or less frequently from the venous system, with an annual incidence of 10–15 per 100,000 population. The incidence increases significantly after age 55 years and doubles with each decade to the age of 80. The haematoma expands following the path of least resistance, usually along white matter tracts, and occasionally into the ventricular system, leading to progressive focal neurological deficit and then deterioration of conscious level secondary to mass effect. Neurological deficit results both from direct tissue destruction and indirectly from local compression and mass effect, usually in proportion to both the volume of haematoma and its rate of expansion. Intraparenchymal haemorrhage can occur at any site, though some areas are more susceptible than others. Eighty percent occur within the cerebral hemispheres while the remaining 20% are infratentorial. Aetiology Hypertension The most important risk factor associated with ICH is hypertension, found in 40–60% of patients. Compared to haemorrhages from other causes, this type of bleed is more frequently fatal, a reflection of both its high incidence and its tendency to occur in critical locations. Hypertensive bleeds most commonly occur in deep white matter (36%), pons (11%) and cerebellum (8%), regions that are variously supplied by the lenticulostriate branches of the middle cerebral artery or the paramedian branches of the basilar artery. Non hypertensive intracerebral haemorrhage Other conditions important in the aetiology of ICHs are: aneurysms (20%), vascular malformations (5–7%), coagulopathies (5–7%), tumours (1–11%), sporadic cerebral amyloid angiopathy and haemorrhagic infarction. Non medicinal use of cocaine and amphetamines may cause ICH, although there is often an underlying vascular malformation in these cases. 122
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Other causes Cerebral amyloid angiopathy, characterised by deposition of amyloid in the media and adventitia of medium-sized hemispheric vessels, is a rare but important cause of recurrent or multiple superficial haematomas in elderly patients, particularly when there is no history of hypertension. It is estimated that during the seventh decade of life, 10% of the population develops amyloid angiopathy, increasing to 60% by the age of 90. Both legal and illegal substances can cause ICH. Amphetamines are most likely to cause ICH, although cocaine, heroin and pseudoephedrine also predispose to ICH. Haemorrhage is caused either by an acute hypertensive episode associated with ingestion of the drug or by necrotising angiitis, caused by injection of a non-sterile substance.
Aneurysms Aneurysms are saccular or fusiform arterial deformities, the result of dissection and protrusion of the intima through a structural defect in the arterial muscular layer. Typical circle of Willis aneurysms, also known as berry aneurysms, most commonly cause subarachnoid haemorrhage, although this is associated with ICH in 30% of patients. Mycotic aneurysms usually form in smaller cortical arteries when septic emboli lodge in the vessel. This is usually seen in the context of infective endocarditis, where up to 17% of patients develop cerebral emboli. Usually these mycotic aneurysms thrombose, and if the infection has been adequately treated, no further intervention is required. Rarely the aneurysm continues to enlarge or ruptures and intervention is necessary to obliterate the aneurysm. Arterial invasion by tumour or severe atherosclerosis occasionally lead to aneurysmal formation, although rupture is rare.
Clinical presentation Haemorrhage may be divided into a number of categories depending on location. These are deep (centred on basal ganglia structures), lobar, pontine and cerebellar. In all sites hypertension remains the most important risk factor and whilst amyloid angiopathy gives rise to lobar and not deep haemorrhage, hypertension is still the most important risk in lobar haemorrhage. Deep haematomas may be centred on the putamen, caudate or thalamus. In putaminal haemorrhage, the picture is of contralateral hemiparesis and conjugate deviation of the eyes towards the side of the haematoma. These haematomas may rupture into the ventricles leading to intraventricular haemorrhage. Caudate haemorrhage is much rarer and small, haematomas may readily rupture into the ventricles. When the lesion is large the picture is similar to putaminal haemorrhage but if small, haematomas may present like subarachnoid haemorrhage with acute headache and meningism with little in the way of focal signs. Thalamic haemorrhage predominantly produces sensory change in the contralateral limbs. Lobar haemorrhages, typically subcortical, produce signs appropriate to their location. In the frontal lobe, eye deviation and contralateral hemiparesis is common. In the central region hemisensory loss is found, associated with dysphasia in the dominant hemisphere. Parietal lobe haemorrhages cause hemisensory loss and neglect/inattention syndromes. Bleeding into the dominant temporal lobe results in a fluent dysphasia with poor comprehension secondary to damage of Wernickes area. The classic picture for a pontine haematoma is of coma associated with pin point pupils, loss of horizontal eye movements and quadraparesis. Hyperpyrexia and irregular respiratory patterns ensue. Cerebellar haemorrhage accounts for 10% of all primary intracerebral haematomas. It is important to recognise as it may result in secondary fatal brainstem compression and hydrocephalus. The usual picture is of acute headache and vomiting with unilateral ataxia. Unilateral gaze paresis in association with ataxia or in isolation may occur. When brainstem compression is present from the onset or later develops the picture looks more like one of pontine haemorrhage.
Vascular malformations Other vascular malformations that cause ICH include arteriovenous malformations (AVMs), cavernous malformations and capillary telangiectasia. AVMs are characterised by a complex tangle of abnormal arteries and veins which lack a capillary bed, creating an arteriovenous shunt. Although considerably less common than intracranial aneurysms, with a prevalence of 0.14–0.5% AVMs are an important cause of haemorrhage in the under 40 years age group. In most instances haemorrhage is intracerebral, although subarachnoid or intraventricular may result from rupture of a pial-based AVM or from the rupture of an intraparenchymal bleed through the pial surface. In contrast to aneurysms, SAH from AVM rupture is rarely associated with vasospasm. In addition, recurrent haemorrhage within the first two weeks of AVM rupture occurs in only 1% of patients. The treatment of AVMs is primarily intended to eradicate the risk of potential haemorrhage. Cavernous malformations (CM), also called cavernous angiomas, cavernomas or cavernous haemangiomas, have a prevalence of 0.4% with a peak incidence in the fourth and fifth decades of life. Overall, they account for 10% of all symptomatic intracranial vascular abnormalities. They can be familial and are often multiple. The frequency of haemorrhage among those who present either incidentally or with seizures is approximately 0.4–2% per year. Coagulopathies One of the most important and potentially treatable causes is anticoagulation, especially when poorly controlled and combined with other risk factors. Intracerebral haemorrhage is the primary complication of anticoagulation therapy, with approximately 2% of all such patients developing bleeds. These types of haemorrhages tend to occur in cortical and subcortical regions, especially in the cerebellum. Any patients on anticoagulants with new focal neurology must be assumed to have bled until proven otherwise with urgent cranial imaging. In those that have bled, anticoagulation should be immediately reversed. Other causes of coagulopathy, including thrombocytopaenia, leukaemia and liver and renal failure, may also cause similar problems. Patients with coagulopathy are also much more likely to bleed into cerebral infarcts.
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Management In primary management at correcting hypertension 123
intracerebral haemorrhage, general supportive issues are important. Medical treatment is aimed any underlying systemic disorder such as severe or coagulopathy, as well as preventing or limiting
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Neurosurgery
secondary complications such as pulmonary emboli, myocardial infarction and pneumonia. Frequent neurological assessments, as well as serial CT scans, are necessary particularly early in the clinical course when management can be modified accordingly. Anticoagulant related haematomas often present as slowly evolving lesions. It is virtually always a mistake if they are small at initial imaging not to immediately reverse warfarin as delay may have devastating consequences. This maxim includes patients with prosthetic valves as the benefit risk ratio is much in favour of anticoagulation reversal for a period of two weeks, after which the rebleeding rate is considerably lower. The rate of systemic embolism from thrombus on the prosthetic valve during this period is small. Neuroimaging is an essential investigation. Acutely a CT is performed to distinguish infarction from haemorrhage or to reveal mimics of the stroke syndrome such as tumour or subdural haematoma. The sensitivity of CT in identifying haemorrhage acutely is far greater than MRI and is therefore often the preferred imaging technique at presentation. In appropriate patients it is necessary to exclude underlying vascular malformations with angiography. Neurosurgical management of intracerebral haemorrhage varies. The optimal management of this form of stroke is unclear from the evidence, although the recent STICH, Surgical Trial in Intracerebral Haemorrhage, trial suggested no significant benefit to surgical evacuation.3 This is however being re-examined looking specifically at lobar haemorrhages. Few neurosurgeons will tackle deep-seated basal ganglia haematomas unless under exceptional circumstances, in the main because the associated morbidity is significant. There is however a much lower threshold for evacuation of life threatening cerebellar haematomas large enough to cause brainstem compression and secondary obstructive hydrocephalus and superficial lobar haematomas that are causing marked mass effect. Treatment modalities for underlying vascular malformations include operative resection, endovascular embolisation and stereotactic radiosurgery, either alone or in combination.
of posthaemorrhagic complications such as cerebral oedema, hydrocephalus and raised intracranial pressure, as well as systemic complications such as pulmonary embolus, myocardial infarction and pneumonia. Overall however the 30 day mortality for supra and infratentorial intracerebral haemorrhage is 58% and 31% respectively.
Intraventricular haemorrhage An intraventricular haemorrhage often mimics SAH with headache, vomiting, neck stiffness and a depressed level of consciousness. There may be associated pyramidal signs, particularly if caused by rupture of a parenchymal haematoma into the ventricular system. This is particularly the case with a caudate haemorrhage, as this nucleus lies adjacent to the ventricular margin. Other causes include coagulopathy (including anticoagulation), aneurysmal rupture or a subependymal angioma. The presence of acute haemorrhage within the ventricular system does predispose the patient to the development of hydrocephalus, either obstructive or communicating. If there is an associated significant depression of level of consciousness, this can be treated by the insertion of an external ventricular drain and in the chronic situation, a ventriculo-peritoneal shunt. ◆
References 1 Pickard JD, Murray GD, Illingworth R, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989; 298(6674): 636–42. 2 Molyneux A, Kerr R, Ly-Mee Y, et al. International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups and aneurysm occlusion. Lancet 2005; 366: 809–17. 3 Mendelow AD, Gregson BA, Fernandes HM, et al. STICH investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005; 365(9457): 387–97.
Prognosis The prognosis of ICH depends primarily on the location and size of the haematoma. These factors are closely followed by the patient’s age and the development and severity
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Spontaneous intracranial haemorrhage
Sites and causes of intracranial haemorrhage
Joan P Grieve
Extradural
Almost exclusively traumatic
Subdural
Trauma (may be minor) Anticoagulation/Clotting disorders Aneurysm (rarely) Secondary to subarachnoid or intraparenchymal haemorrhage Trauma Aneurysms Hypertension Anticoagulants Amyloid angiopathy Arteriovenous malformations Aneurysms Cavernous angiomas Amphetamine/cocaine ingestion Infective endocarditis Tumours Disseminated intravascular coagulation Venous thrombosis Cerebral vasculitis Trauma Anticoagulants Secondary to subarachnoid or intraparenchymal haemorrhage Subependymal vascular malformation
Subarachnoid
Abstract
Intracerebral
Intracranial haemorrhage, the pathological accumulation of blood within the cranial vault, may occur within brain parenchyma or the surrounding meningeal spaces and is most commonly caused by trauma. Spontaneous intracranial haemorrhage generally occurs within the subarachnoid (SAH), intracerebral (ICH) and intraventricular (IVH) spaces. SAH usually occurs as a result of aneurysmal rupture and happens with an annual incidence of 10/100 000 population. Non-traumatic ICH accounts for 8–13% of all strokes and results from a wide spectrum of disorders. However it most commonly results from hypertensive damage to blood vessel walls (e.g., hypertension, eclampsia, drug abuse). ICH is more likely to result in death or major disability than ischaemic stroke or SAH. Symptoms vary depending on the location of the bleed and the amount of brain tissue affected. The symptoms usually develop suddenly and without warning, although they may occasionally develop in a stepwise, episodic manner or they may get progressively worse, either as a result of further haemorrhage (a particular risk in aneurysmal SAH) or the development of oedema surrounding a focal haematoma. The presence of blood within the ventricular system also predisposes the patient to deterioration from secondary hydrocephalus. This may be of acute onset but may also develop much more insidiously. Management is generally supportive. The identification of any underlying structural vascular abnormality, particularly when an intracranial aneurysm is suspected, is important, allowing early treatment and the prevention of rehaemorrhage.
Intraventricular
Table 1
Subarachnoid haemorrhage A subarachnoid haemorrhage (SAH) involves the accumulation of blood between the arachnoid and the pia mater. The main cause of non-traumatic SAH is rupture of an intracranial aneurysm, which accounts for 85% of cases. It is a devastating condition with an overall case fatality of 50% (including pre hospital deaths), with 30% of survivors being left dependent because of major neurological deficits. Five percent of cases are caused by rare conditions, including arteriovenous malformations (including spinal AVMs), cerebral vasculitides, tumours, dural arteriovenous fistula, dural sinus thrombosis, carotid or vertebral artery dissections, coagulopathy and drugs. The remaining 10% of patients will have no obvious cause for their haemorrhage and a normal angiogram. The annual incidence of aneurysmal SAH is approximately 10 per 100 000, increasing to a peak incidence at 55–60 years. There is a female preponderance, with reported male-to-female ratios of 1:1.8. Most cases of aneurysmal SAH are sporadic; however there is considerable evidence to support the role of genetic factors in the development of intracranial aneurysms. There is a strong association between intracranial aneurysms and heritable connective tissues diseases, such as autosomal dominant polycystic kidney disease, Marfan’s syndrome, pseudoxanthoma elasticum, Ehlers-Danlos syndrome and alpha-1 antitrypsin deficiency.
Keywords intracerebral haemorrhage; intraventricular haemorrhage; spontaneous intracranial haemorrhage; subarachnoid haemorrhage
Introduction Intracranial haemorrhage may be classified according to location (Table 1), the commonest cause of all intracranial haemorrhage being trauma. Spontaneous intracranial haemorrhage (without accompanying trauma) however most commonly occurs in the form of subarachnoid haemorrhage, intracerebral haemorrhage and intraventricular haemorrhage. Rarely a subdural haematoma can develop when a subarachnoid or intraparenchymal bleed extends into the subdural space through a tear in the arachnoid.
Joan P Grieve MD FRCS(SN) is a Consultant Neurosurgeon at The National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
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Most aneurysms arise from the anterior circulation with 85–95% from the internal carotid artery (ICA) system and 5–15% the posterior circulation. Anterior communicating artery aneurysms are the commonest lesion, particularly in men (46.1% in men versus 26.6% in women). Also common are aneurysms arising from the ICA, especially in women (36.8% compared with 18% of men). Posterior communicating artery aneurysms are found in 20–25% of individuals whilst middle cerebral artery aneurysms are found in 15–20%. Within the posterior circulation, 10% arise from the basilar artery, the basilar tip being the most common site, followed by superior cerebellar junction and 5% arise from the vertebral artery, posterior inferior cerebellar artery being the most common site. Ten to 15% of cases will have a normal angiogram. Of these, 65% will have a distinctive pattern of subarachnoid blood lying in the prepontine or perimesencephalic cisterns. These patients tend to be younger, non-hypertensive, of better clinical grade and more often male than SAH patients with positive angiograms. The aetiology of these cases is unclear but may be due to venous haemorrhage. The overall prognosis tends to be good, partly because rebleeding is rare and few patients develop delayed ischaemic deficit. However the diagnosis should only be entertained with caution as 10% of vertebrobasilar aneurysms present with a similar distribution of blood.
In addition, familial intracranial aneurysms account for 7–20% of patients. Environmental factors have been extensively studied and cigarette smoking is the only factor consistently identified raising the risk 3–10 times. Hypertension is also almost certainly important but to a lesser degree. It seems that hypertension and smoking act as synergistic risk factors. The use of sympathomimetic drugs, such as cocaine and metamphetamine, tend to increase the incidence and decrease the age at which aneurysmal rupture occurs; aneurysmal size at rupture also tends to be smaller. Clinical features The cardinal clinical feature is of a “thunderclap headache”. Headache is present in up to 97% of patients and is often accompanied by nausea and vomiting (77%). Consciousness is frequently altered, with confusion and lethargy in 30%, transient loss of consciousness in one third and coma in 17%. Neurological abnormalities are seen in 64% of cases with focal signs such as hemiparesis, IIIrd or VIth nerve palsies in 21%. Focal deficits may be caused by intraparenchymal haemorrhage. A painful pupil-involving IIIrd nerve palsy without headache is usually taken as imminent rupture of a posterior communicating artery aneurysm and should therefore be dealt with promptly. Investigation CT scanning is mandatory in those with suspected SAH, generally revealing diffuse blood of a symmetrical distribution around the basal cisterns, sylvian fissures and cortical sulci. Modern generation CT will demonstrate the presence of blood in 98% of patients scanned within 48 hours. However blood is rapidly cleared from the CSF and the sensitivity gradually decreases. Head CT scanning can also demonstrate secondary hydrocephalus, cerebral ischaemia or infarction, mid-line shift or re-haemorrhage. If clinical suspicion is strong and the CT is normal, lumbar puncture, preferably by an experienced operator, should be performed. If clinically appropriate this should be delayed for 12 hours from the ictus to allow time for xanthochromia (yellow discolouration) to develop. Xanthochromia of the supernatant is diagnostic of SAH. This must be determined by spectrophotometry rather than visual inspection. Negative CSF is very helpful in excluding SAH but bloodstained CSF may result from a traumatic tap. A decrease in the number of red cells from bottle one to three is a very unreliable way of differentiating SAH from a traumatic tap. It should be remembered that patients may have had both SAH and a traumatic tap. Conventional MRI is not sensitive to acute haemorrhage as there is too little methaemoglobin for haemorrhage to be easily differentiated from CSF. Visualisation of blood on MRI is, however, better after 4–7 days and is therefore excellent at demonstrating subacute to remote SAH, when CT sensitivity decreases. In patients with either equivocal or diagnostic CT/lumbar puncture, some form of structural imaging is undertaken to identify the ruptured aneurysm. Digital subtraction angiography (DSA) has been the gold standard investigation until recently, but advances in three-dimensional CT angiography have meant that it now has a sensitivity and specificity approaching that of DSA (sensitivity of 77–97% and specificity of 87–100%). Its non-invasive nature may ultimately obviate the need for cerebral angiography with its inherent risks, at least as a first line investigation.
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Initial management General supportive care should be instituted. Stabilisation of the patient, with optimisation for aneurysm treatment, together with prevention of secondary cerebral insults is achieved by ensuring adequate ventilation and oxygenation, normovolaemia and haemodynamic stability and control of intracranial pressure. Frequent neurological examination is required in order to identify any neurological deterioration requiring further investigation or management. Bed rest is generally recommended until aneurysm treatment is undertaken. Nimodipine, a calcium channel antagonist, has been shown to reduce the risk of cerebral infarction due to vasospasm by 34% and, as a result, poor outcome following SAH by 40%.1 A dose of 60 mg 4-hourly either orally or via a nasogastric tube is used. With an unsecured aneurysm, gentle volume expansion with slight haemodilution may help to return the circulating volume to normal and prevent or minimise the effects of vasospasm; however hypertension should be avoided. Once the aneurysm is secured, hypertension is allowed, but there is no agreement on the range. Analgesia is often required. Aneurysmal treatment Currently the two main treatment options for securing of an aneurysm are neurosurgical clipping and endovascular coiling. Traditionally craniotomy and clipping of the aneurysm has been the preferred method, although the timing of surgery has been debated. The rebleeding rate from aneurysms is particularly high in the first two weeks and then declines. This early high rebleed rate, which may have devastating complications, together with more recent improvements in microsurgical techniques is the reason why early intervention is generally favoured. Securing the aneurysm will also facilitate the treatment of complications such as cerebral vasospasm. 121
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(low-intravascular volume) or syndrome of inappropriate anti-diuretic hormone (SIADH) (normal or increased intravascular volume), if left untreated has a high associated morbidity and mortality. Their distinction is important as cerebral salt-wasting is treated by aggressive fluid administration and sodium supplements, whilst treatment of SIADH involves fluid restriction. Fluid restriction of patients with cerebral salt wasting will worsen their hypovolaemia and will therefore predispose them to vasospasm.
The Guglielmi Detachable Coil (GDC) has been available since 1991 and has been increasingly used in clinical practice. Detachable platinum coils are delivered endovascularly into the aneurysm. Once the correct position within the aneurysm has been achieved, the coil is detached from this wire. Multiple coils of various lengths and thicknesses are often packed into the aneurysm to exclude it from the circulation. The results of the International Subarachnoid Aneurysm Trial (ISAT) suggest that 23.5% of patients treated by endovascular means were dead or dependent at 1 year, compared with 30.9% allocated to neurosurgery, an absolute risk reduction of 7.4%.2 The early survival advantage is maintained for up to 7 years and was significant despite a higher late rebleeding rate. However, many aneurysms are not equally suitable for either microsurgical clipping or endovascular coiling. In individual cases, several factors – such as patient’s age and overall medical condition and the aneurysm’s location, size, morphology and relationship to adjacent vessels – need to be analysed in the context of a multidisciplinary team to decide on the most appropriate treatment.
Outcome Pre-hospital mortality is 3–26%, with an overall mortality of 45–60% in the first 30 days after SAH. Overall morbidity is quoted as 25–33%, caused in the majority of patients by vasospasm, although initial deficits and intervention also contribute. The major predictive factors for a poor outcome are level of consciousness on admission, age and amount of blood on presenting CT. More than 50% of survivors report problems with memory, mood or neuropsychological function. Despite this half to two thirds of survivors are able to return to work one year after presentation.
Complications If unprotected, 15–20% of patients will rebleed in the first 2 weeks, carrying with it a significant mortality (50–75%) and risk of permanent neurological disability. There appears to be an initial peak of rehaemorrhage in the first 48 hours of approximately 4%, which rapidly plateaus to 1–2% per day until 40 days post-haemorrhage. After 6 months there is a long-term risk of further haemorrhage of 3% per year. The risk of rebleed is increased with poor clinical grade, posterior circulation lesions, hypertension, elderly patients and abnormal haemostatic parameters. Symptomatic vasospasm (synonymous with delayed ischaemic deficit) occurs in 20–30% of patients and is at its worst 3–14 days following the haemorrhage. The mechanism by which vasospasm is effected is poorly understood. A multifactorial origin is most probable with the liberation of spasmogenic metabolites during clot lysis in the basal cisterns and the impairment of cerebral vasodilatation related to endothelial dysfunction and structural changes in the arterial wall. Following SAH there appears to be an imbalance between the vasodilating and vasoconstricting influences that are normally present. If severe, vasospasm can lead to cerebral infarction. The severity and distribution of vasospasm are related to the amount and site of subarachnoid blood. Diagnosis can be difficult and is often made after exclusion of other causes of neurological deterioration such as hydrocephalus, electrolyte disturbance, seizures or a rebleed. Once identified, patients are treated with hypervolaemia and induced hypertension. In those patients refractory to medical treatment, transluminal angioplasty or vasodilator infusion (for example papaverine or nifedipine) can be used to improve both angiographic appearances and the patient’s clinical condition. Symptomatic hydrocephalus is seen in 10–35% of patients. This may be either obstructive, caused by an intraventricular clot, or communicating, caused when the subarachnoid blood blocks CSF reabsorption through the arachnoid villi. Acutely it is treated by a period of external ventricular drainage but in the longer term, 10–15% of patients will require placement of a permanent ventriculo-peritoneal shunt. Electrolyte disturbances, most commonly of sodium, are seen in 28%. Hyponatraemia, caused by cerebral salt-wasting
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Intracerebral haemorrhage Spontaneous intracerebral haemorrhage (ICH) results from intracerebral arterial rupture, particularly of perforating vessels, or less frequently from the venous system, with an annual incidence of 10–15 per 100,000 population. The incidence increases significantly after age 55 years and doubles with each decade to the age of 80. The haematoma expands following the path of least resistance, usually along white matter tracts, and occasionally into the ventricular system, leading to progressive focal neurological deficit and then deterioration of conscious level secondary to mass effect. Neurological deficit results both from direct tissue destruction and indirectly from local compression and mass effect, usually in proportion to both the volume of haematoma and its rate of expansion. Intraparenchymal haemorrhage can occur at any site, though some areas are more susceptible than others. Eighty percent occur within the cerebral hemispheres while the remaining 20% are infratentorial. Aetiology Hypertension The most important risk factor associated with ICH is hypertension, found in 40–60% of patients. Compared to haemorrhages from other causes, this type of bleed is more frequently fatal, a reflection of both its high incidence and its tendency to occur in critical locations. Hypertensive bleeds most commonly occur in deep white matter (36%), pons (11%) and cerebellum (8%), regions that are variously supplied by the lenticulostriate branches of the middle cerebral artery or the paramedian branches of the basilar artery. Non hypertensive intracerebral haemorrhage Other conditions important in the aetiology of ICHs are: aneurysms (20%), vascular malformations (5–7%), coagulopathies (5–7%), tumours (1–11%), sporadic cerebral amyloid angiopathy and haemorrhagic infarction. Non medicinal use of cocaine and amphetamines may cause ICH, although there is often an underlying vascular malformation in these cases. 122
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Other causes Cerebral amyloid angiopathy, characterised by deposition of amyloid in the media and adventitia of medium-sized hemispheric vessels, is a rare but important cause of recurrent or multiple superficial haematomas in elderly patients, particularly when there is no history of hypertension. It is estimated that during the seventh decade of life, 10% of the population develops amyloid angiopathy, increasing to 60% by the age of 90. Both legal and illegal substances can cause ICH. Amphetamines are most likely to cause ICH, although cocaine, heroin and pseudoephedrine also predispose to ICH. Haemorrhage is caused either by an acute hypertensive episode associated with ingestion of the drug or by necrotising angiitis, caused by injection of a non-sterile substance.
Aneurysms Aneurysms are saccular or fusiform arterial deformities, the result of dissection and protrusion of the intima through a structural defect in the arterial muscular layer. Typical circle of Willis aneurysms, also known as berry aneurysms, most commonly cause subarachnoid haemorrhage, although this is associated with ICH in 30% of patients. Mycotic aneurysms usually form in smaller cortical arteries when septic emboli lodge in the vessel. This is usually seen in the context of infective endocarditis, where up to 17% of patients develop cerebral emboli. Usually these mycotic aneurysms thrombose, and if the infection has been adequately treated, no further intervention is required. Rarely the aneurysm continues to enlarge or ruptures and intervention is necessary to obliterate the aneurysm. Arterial invasion by tumour or severe atherosclerosis occasionally lead to aneurysmal formation, although rupture is rare.
Clinical presentation Haemorrhage may be divided into a number of categories depending on location. These are deep (centred on basal ganglia structures), lobar, pontine and cerebellar. In all sites hypertension remains the most important risk factor and whilst amyloid angiopathy gives rise to lobar and not deep haemorrhage, hypertension is still the most important risk in lobar haemorrhage. Deep haematomas may be centred on the putamen, caudate or thalamus. In putaminal haemorrhage, the picture is of contralateral hemiparesis and conjugate deviation of the eyes towards the side of the haematoma. These haematomas may rupture into the ventricles leading to intraventricular haemorrhage. Caudate haemorrhage is much rarer and small, haematomas may readily rupture into the ventricles. When the lesion is large the picture is similar to putaminal haemorrhage but if small, haematomas may present like subarachnoid haemorrhage with acute headache and meningism with little in the way of focal signs. Thalamic haemorrhage predominantly produces sensory change in the contralateral limbs. Lobar haemorrhages, typically subcortical, produce signs appropriate to their location. In the frontal lobe, eye deviation and contralateral hemiparesis is common. In the central region hemisensory loss is found, associated with dysphasia in the dominant hemisphere. Parietal lobe haemorrhages cause hemisensory loss and neglect/inattention syndromes. Bleeding into the dominant temporal lobe results in a fluent dysphasia with poor comprehension secondary to damage of Wernickes area. The classic picture for a pontine haematoma is of coma associated with pin point pupils, loss of horizontal eye movements and quadraparesis. Hyperpyrexia and irregular respiratory patterns ensue. Cerebellar haemorrhage accounts for 10% of all primary intracerebral haematomas. It is important to recognise as it may result in secondary fatal brainstem compression and hydrocephalus. The usual picture is of acute headache and vomiting with unilateral ataxia. Unilateral gaze paresis in association with ataxia or in isolation may occur. When brainstem compression is present from the onset or later develops the picture looks more like one of pontine haemorrhage.
Vascular malformations Other vascular malformations that cause ICH include arteriovenous malformations (AVMs), cavernous malformations and capillary telangiectasia. AVMs are characterised by a complex tangle of abnormal arteries and veins which lack a capillary bed, creating an arteriovenous shunt. Although considerably less common than intracranial aneurysms, with a prevalence of 0.14–0.5% AVMs are an important cause of haemorrhage in the under 40 years age group. In most instances haemorrhage is intracerebral, although subarachnoid or intraventricular may result from rupture of a pial-based AVM or from the rupture of an intraparenchymal bleed through the pial surface. In contrast to aneurysms, SAH from AVM rupture is rarely associated with vasospasm. In addition, recurrent haemorrhage within the first two weeks of AVM rupture occurs in only 1% of patients. The treatment of AVMs is primarily intended to eradicate the risk of potential haemorrhage. Cavernous malformations (CM), also called cavernous angiomas, cavernomas or cavernous haemangiomas, have a prevalence of 0.4% with a peak incidence in the fourth and fifth decades of life. Overall, they account for 10% of all symptomatic intracranial vascular abnormalities. They can be familial and are often multiple. The frequency of haemorrhage among those who present either incidentally or with seizures is approximately 0.4–2% per year. Coagulopathies One of the most important and potentially treatable causes is anticoagulation, especially when poorly controlled and combined with other risk factors. Intracerebral haemorrhage is the primary complication of anticoagulation therapy, with approximately 2% of all such patients developing bleeds. These types of haemorrhages tend to occur in cortical and subcortical regions, especially in the cerebellum. Any patients on anticoagulants with new focal neurology must be assumed to have bled until proven otherwise with urgent cranial imaging. In those that have bled, anticoagulation should be immediately reversed. Other causes of coagulopathy, including thrombocytopaenia, leukaemia and liver and renal failure, may also cause similar problems. Patients with coagulopathy are also much more likely to bleed into cerebral infarcts.
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Management In primary management at correcting hypertension 123
intracerebral haemorrhage, general supportive issues are important. Medical treatment is aimed any underlying systemic disorder such as severe or coagulopathy, as well as preventing or limiting
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secondary complications such as pulmonary emboli, myocardial infarction and pneumonia. Frequent neurological assessments, as well as serial CT scans, are necessary particularly early in the clinical course when management can be modified accordingly. Anticoagulant related haematomas often present as slowly evolving lesions. It is virtually always a mistake if they are small at initial imaging not to immediately reverse warfarin as delay may have devastating consequences. This maxim includes patients with prosthetic valves as the benefit risk ratio is much in favour of anticoagulation reversal for a period of two weeks, after which the rebleeding rate is considerably lower. The rate of systemic embolism from thrombus on the prosthetic valve during this period is small. Neuroimaging is an essential investigation. Acutely a CT is performed to distinguish infarction from haemorrhage or to reveal mimics of the stroke syndrome such as tumour or subdural haematoma. The sensitivity of CT in identifying haemorrhage acutely is far greater than MRI and is therefore often the preferred imaging technique at presentation. In appropriate patients it is necessary to exclude underlying vascular malformations with angiography. Neurosurgical management of intracerebral haemorrhage varies. The optimal management of this form of stroke is unclear from the evidence, although the recent STICH, Surgical Trial in Intracerebral Haemorrhage, trial suggested no significant benefit to surgical evacuation.3 This is however being re-examined looking specifically at lobar haemorrhages. Few neurosurgeons will tackle deep-seated basal ganglia haematomas unless under exceptional circumstances, in the main because the associated morbidity is significant. There is however a much lower threshold for evacuation of life threatening cerebellar haematomas large enough to cause brainstem compression and secondary obstructive hydrocephalus and superficial lobar haematomas that are causing marked mass effect. Treatment modalities for underlying vascular malformations include operative resection, endovascular embolisation and stereotactic radiosurgery, either alone or in combination.
of posthaemorrhagic complications such as cerebral oedema, hydrocephalus and raised intracranial pressure, as well as systemic complications such as pulmonary embolus, myocardial infarction and pneumonia. Overall however the 30 day mortality for supra and infratentorial intracerebral haemorrhage is 58% and 31% respectively.
Intraventricular haemorrhage An intraventricular haemorrhage often mimics SAH with headache, vomiting, neck stiffness and a depressed level of consciousness. There may be associated pyramidal signs, particularly if caused by rupture of a parenchymal haematoma into the ventricular system. This is particularly the case with a caudate haemorrhage, as this nucleus lies adjacent to the ventricular margin. Other causes include coagulopathy (including anticoagulation), aneurysmal rupture or a subependymal angioma. The presence of acute haemorrhage within the ventricular system does predispose the patient to the development of hydrocephalus, either obstructive or communicating. If there is an associated significant depression of level of consciousness, this can be treated by the insertion of an external ventricular drain and in the chronic situation, a ventriculo-peritoneal shunt. ◆
References 1 Pickard JD, Murray GD, Illingworth R, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989; 298(6674): 636–42. 2 Molyneux A, Kerr R, Ly-Mee Y, et al. International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups and aneurysm occlusion. Lancet 2005; 366: 809–17. 3 Mendelow AD, Gregson BA, Fernandes HM, et al. STICH investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005; 365(9457): 387–97.
Prognosis The prognosis of ICH depends primarily on the location and size of the haematoma. These factors are closely followed by the patient’s age and the development and severity
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