The three main subtypes of stroke
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1 Neurology 55 Spontaneous intracerebral haemorrhage in the elderly Spontaneous Intracerebral Haemorrhage (ICH) is defined as bleeding into the brain parenchyma without accompanying trauma. This condition commonly affects the elderly and may potentially lead to severe disability or death. In this article, Dr Elliot Epstein discusses the advances in the management of ICH throughout the last decade that will hopefully lead to improved outcome for afflicted patients. DR ELLIOT EPSTEIN is a Consultant Stroke Physician at Walsall Manor Hospital The three main subtypes of stroke are ischaemic stroke, subarachnoid haemorrhage and spontaneous intracerebral haemorrhage (ICH), the latter accounting for approximately 10 per cent of all strokes. A Swedish study reported that the overall incidence of ICH per 100,000 per year was 33.5 for men and 26.6 for women 1. Incidence rises sharply with increasing age and is estimated at 121 per 100,000 per year for the age group compared to only 35 per 100,000 per year for those aged years. Interestingly, incidence appears to have fallen over the last 20 years, possibly a reflection of improved control of hypertension 2. Causes Chronic arterial hypertension is frequently the cause of ICH in the elderly. Hypertension may lead to degenerative changes or to micro aneurysm formation in small perforating arterioles in the deep structures of the brain, and subsequent rupture leads to ICH. The basal ganglia, pons, cerebellum and thalamus are the sites frequently affected (Table 1). Another important cause of ICH in the elderly is amyloid angiopathy. This condition is characterised by deposition of amyloid protein in the walls of the small arteries and arterioles, and it usually leads to haemorrhage in the cortical or subcortical regions of the brain (known as lobar haemorrhage). Arteriovenous malformations and saccular/ berry aneuryms frequently cause ICH in younger adults. Arteriovenous malformations are conglomerates of arteries and veins, without a capillary network between them. Saccular and berry aneurysms are named due to their resemblance of a sack attached to one side of the artery by a narrow neck. Anticoagulant drugs used to treat atrial fibrillation or venous thrombosis may predispose to ICH, and the risk is particularly great if the International Normalised Ratio (INR) is allowed to rise above therapeutic levels 3. Aspirin, particularly if used in combination with clopidogrel for secondary prevention of ischaemic stroke 4, is also associated with an increased risk of ICH. ICH is also a recognised complication of thrombolytic therapy for the treatment of myocardial infarction and ischaemic stroke. Bleeding into a brain tumour is an important cause of ICH in all age groups. Clinical presentation The clinical features vary depending upon the april 2006 / midlife and beyond / geriatric medicine
2 56 Neurology Table 1. Causes of ICH Acute/chronic hypertension Amyloid angiopathy Brain tumour Anticoagulants and antithrombotic medication Thrombocytopenia Alcohol: acute binge drinking and chronic abuse Haemorrhagic transformation of a cerebral infarct Intracranial venous thrombosis Saccular/berry aneurysm Cocaine, amphetamine usage Bacterial meningitis, vasculitis. site and extent of haemorrhage. Frequently, the patient presents with sudden onset of loss of consciousness or a convulsion, and may be discovered unconscious in their home by carers. Nausea, vomiting and headache are common. On clinical examination, hemiparesis and neck stiffness may be present. Cerebellar haemorrhage may present with vertigo, ataxia, occipital headache and declining level of consciousness. A thorough clinical evaluation should be performed in all patients and this may help identify the cause of ICH. It is particularly important to establish if the patient was taking anticoagulant medication or if head trauma was sustained. If level of consciousness is reduced, hospital staff should contact family or carers to obtain the medical history. Investigations The purpose of brain imaging is to assist the distinction of cerebral haemorrhage from infarct and to exclude other conditions such as tumour and subdural haematoma. Brain imaging should be requested urgently in certain situations: for example, if the patient has reduced level of consciousness or is taking anticoagulant medication. For other patients, a brain scan should ideally be performed within 24 hours 5. In the past, Computerised Tomography (CT) scan has been considered more accurate at the identification geriatric medicine / midlife and beyond / april 2006
3 Neurology 57 of acute ICH compared to Magnetic Resonance Imaging (MRI). However, this situation may change as MRI techniques improve 6. If a patient presents 10 days or more following onset of stroke then CT may be unreliable at the differentiation of infarct from haemorrhage and, in this scenario, MRI is the imaging modality of choice 5. Other important initial investigations include clotting studies and platelet count. Acute clinical management Many of the principles of management of ischaemic and haemorrhagic stroke are similar. Patients with moderate or severe stroke should be cared for on a dedicated acute stroke unit, and in this environment prospects for recovery are greater compared to care on a general medical ward 5,7. During the acute phase, patients should be monitored frequently. For patients that present with reduced level of consciousness or respiratory failure, intubation and ventilation may be appropriate and discussion with the critical care team should be considered. If oxygen saturations are low, oxygen should be prescribed and the cause identified and treated. Patients with fever should be assessed for the presence of infection and paracetamol administered. For patients with dysphagia or reduced level of consciousness, the use of intravenous fluids is required to ensure adequate hydration and enteral feeding should be considered. If possible, early mobilisation should be attempted and compressing stockings should be applied to the patient s legs to reduce the risk of venous thrombosis. Hypertension is commonly reported following ICH; however, it is currently not known if blood pressure should be pharmacologically lowered immediately following the acute event. It is possible that elevated blood pressure is necessary to maintain perfusion of the area of potentially salvageable brain tissue that surrounds the haemorrhage (known as the ischaemic penumbra). Hence a sudden fall in arterial blood pressure may april 2006 / midlife and beyond / geriatric medicine
4 58 Neurology reduce perfusion to this region and be detrimental to recovery. Unfortunately, there is an absence of randomised-controlled trials to guide management. It is reasonable not to treat hypertension in the acute setting unless high values are recorded (170/110mmHg) 8, or if features of malignant hypertension are present. Some patients may sustain an ICH whilst taking anticoagulant medication for reasons such as thromboprophylaxis in atrial fibrillation. Reversal of anticoagulation with vitamin K, fresh frozen plasma or factor concentrates may be required in an attempt to arrest progression of haemorrhage. For patients taking anticoagulant medication for a mechanical heart valve, reversal of anticoagulation may lead to an unacceptably high risk of thromboembolus. Specialist advice may be sought from a cardiothoracic unit or haemotologist. Management for venous thromboembolism complicating ICH A particular dilemma is how best to manage patients that develop pulmonary embolus or proximal deep-vein thrombosis in the few weeks following ICH. Anticoagulation is the mainstay treatment of venous thromboembolus but this may increase the risk of recurrent ICH. There is little consensus to guide correct management and the physician may need to balance the risks of anticoagulation with the benefits. One option is to consider insertion of an inferior vena caval filter. However, this procedure is not without complications, such as filter malpositioning or migration. It is also possible for thrombus to subsequently develop proximal to the site of the filter. Haemostatic agents to treat ICH A promising development in the treatment of ICH is based upon the observation that, following ICH, bleeding continues for several hours after the acute event resulting in haematoma expansion. One potential strategy is to administer haemostatic agents following acute ICH to arrest haematoma growth. In one recent randomised-controlled trial, patients sustaining an acute ICH within the previous four hours were assigned to receive Long-term control of hypertension is important, not only to prevent recurrent brain haemorrhage but also to prevent ischaemic stroke and myocardial infarction. recombinant factor VII or placebo 9. The patients recruited had no evidence of a clotting or platelet disorder and were not taking anticoagulant medication. The investigators reported that recombinant factor VII reduced fatality and improved functional dependency at 90 days post ICH, but further research is required before this treatment is to be introduced into clinical practice. Surgical evacuation of haemorrhage Surgical techniques are continually improving and include craniotomy, stereotactic aspiration or endoscopic evacuation. For patients with cerebellar haemorrhage, it is crucial to consider referral to a neurosurgeon as clot evacuation may lead to a successful outcome. Surgical treatment of cerebellar haemorrhage is indicated for those that are shown to have brain stem compression, hydrocephalus as a result of obstruction of the forth ventricle or deteriorating level of consciousness. For patients with supratentorial intracerebral haemorrhage, the advantages of surgical evacuation are not clear. Recently a large randomised-controlled trial concluded there was no benefit of early surgery compared with conservative management for supratentorial intracerebral haemorrhage 10. On sub-group analysis, there was a possible favourable outcome for patients with superficial haematoma as presumably these patients suffer less destruction of brain tissue during surgery. It is possible in the future, with improved surgical techniques, that survival following surgery for supratentorial haemorrhage will be improved. Investigation for an underlying lesion Cerebral haemorrhage may occur at the site of an underlying lesion such as arteriovenous malformation or saccular aneurysm. It is important to identify such lesions early as the patient may be in danger of sustaining a recurrent haemorrhage geriatric medicine / midlife and beyond / april 2006
5 Neurology 59 that may be catastrophic. Cerebral angiography is the gold standard investigation. This procedure involves insertion of a catheter into a large artery, e.g. the femoral artery, and this catheter is subsequently advanced into the carotid artery and a contrast agent is injected. The disadvantage of cerebral angiography is that it is an invasive procedure, occasionally complicated by stroke. The decision to undertake cerebral angiography is based upon the probability of detecting an underlying vascular abnormality. Studies have shown that the chance of angiography detecting such a lesion for hypertensive patients over the age of 45 years with haemorrhage sited in the basal ganglia, thalamus, cerebellum or brain stem is low 11. Hence angiography is not usually recommended for this group of older adults 8. By contrast, for young, normotensive patients with ICH, angiography is more likely to detect a vascular abnormality 8,11. MRI, magnetic resonance angiography and CT angiography are non-invasive investigations and are commonly used as an alternative to cerebral angiography, yet are not accurate for detection of small lesions. For patients admitted to hospital with ICH, it is usually advisable to discuss management with the local neurosurgical unit. If angiography is contemplated it is essential to obtain the views and ultimately consent of the patient. For patients that do not undergo urgent angiography an alternative approach is to perform a CT or MRI six weeks post-event, following clearing of haemorrhage, to identify an underlying lesion. Secondary prevention Long-term control of hypertension is important, not only to prevent recurrent brain haemorrhage but also to prevent ischaemic stroke and myocardial infarction. Blood pressure should be reduced to below 140/85mmHg for non-diabetics and 130/80mmHg for diabetics 5. Appropriate antihypertensive mediation includes ACE inhibitors, thiazide diuretics or the thiazide-like diuretic indapamide. The results of the PROGRESS trial support the use of a combination of perindopril and indapamide for preventing recurrent stroke for both hypertensive and normotensive patients 12. It is important to educate the patient in lifestyle modifications such as undertaking aerobic exercise, avoidance of excess salt, weight reduction if obese and eating a sensible diet. Excess alcohol consumption and binge drinking should be strongly discouraged. Rehabilitation Following acute stroke, rehabilitation is best conducted in a specialist stroke unit. The multidisciplinary team includes nursing and medical staff, physiotherapists, occupational therapists, speech and language therapists and social workers. Team members should liaise closely with each other, and with the patient and carer, to optimise recovery. Many patients require a complex package of care to enable return home. Prognosis Relatives and patients commonly ask questions concerning prognosis shortly after admission to hospital. Low level of consciousness (Glasgow Coma Scale <8) at the time of admission and large volume of haematoma are frequently used as markers of a poor outcome 13. One series reported that at 30 days post ICH, 80 per cent were either dead or moderately/severely disabled 14. However, many physicians are able to recall examples of patients, initially labelled with a terminal prognosis, recover and achieve a good quality of life. It is important to remember that reduced level of consciousness may be related to factors such as sepsis and electrolyte disturbance rather than the degree of brain damage consequent upon haemorrhage. Conclusion Patients presenting with suspected ICH require thorough clinical evaluation and appropriate brain imaging to confirm diagnosis. For selected patients, further investigation may be required to identify an underlying lesion such as tumour, aneurysm or arteriovenous malformation. Patients should usually receive acute treatment and subsequent rehabilitation on a stroke unit with input from a dedicated multidisciplinary team. ICH is potentially a devastating condition, and hopefully in the future there will be progress in therapeutic interventions to reduce disability and mortality GM Conflict of interest: none declared april 2006 / midlife and beyond / geriatric medicine
6 60 Neurology References 1. Nilsson OG, Lindgren A, Stahl N, et al. Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden. J Neurol Neurosurg Psychiatry y 2000; 69(5): Rothwell PM, Coull AJ, Giles MF, et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004; 363(9425): Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial haemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141(10): Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004; 364: Intercollegiate Stroke Working Party. National Clinical Guidelines for Stroke: Second Edition. London: Royal College of Physicians, June Available at: ac.uk/pubs/books/stroke/stroke_ guidelines_2ed.pdf (date last accessed: 01/05/05) 6. Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral haemorrhage: a multicenter study on the validity of stroke imaging. Stroke 2004; 35: Ronning OM, Guldvog B, Stavem K. The benefit of an acute stroke unit in patients with intracranial haemorrhage: a controlled trial. J Neurol Neurosurg Psychiatry 2001; 70(5): Broderick JP, Adams HP Jr, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999; 30(4): Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005; 352(8): Mendelow AD, Gregson BA, Fernandes HM, et al. 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): Zhu XL, Chan MS, Poon WS. Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography? A prospective study of 206 cases and review of the literature. Stroke 1997; 28: PROGRESS Collaborative Group. Randomised trial of a perindoprilbased blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient attack. Lancet 2001; 358: Broderick JP, Brott TG, Duldner JE, et al. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993; 24(7): Barber M, Roditi G, Stott DJ, Langhorne P. Poor outcome in primary intracerebral haemorrhage: results of a matched comparison. Postgrad Med J 2004; 80(940): Key points > ICH frequently causes severe disability and death in the elderly. > Chronic hypertension and overanticoagulation are important, and potentially preventable, causes of ICH. > Essential initial investigations include appropriate brain imaging, clotting studies and platelet count. > Surgical evacuation for cerebellar haemorrhage is indicated if there is brain stem compression or hydrocephalus. For patients with supratentorial haemorrhage, the benefit of surgery is not clear. > Some patients with ICH may have an underlying lesion such as tumour, aneurysm or arteriovenous malformation and further investigations may be required. geriatric medicine / midlife and beyond / april 2006
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