CEREBRAL THROMBOSIS

Atherosclerosis is the major cause of major arterial occlusion and most often produces symptoms if it occurs at the bifurcation of the carotid artery or the carotid syphon. Progressive plaque formation causes narrowing and forms a nidus for platelet aggregation and thrombus formation. Ulceration and rupture of the plaque expose its thrombogenic lipid core, activating the clotting cascade. Hypertension and diabetes mellitus are common causes of smaller arterial thrombosis. Rarer causes of thrombosis include any disease resulting in vasculitis, vertebral or carotid artery dissection (either spontaneous or posttraumatic) or carotid occlusion by strangulation or systemic hypotension after cardiac arrest. Cerebral venous thrombosis, responsible for less than 1% of strokes, may occur in hypercoagulable states such as dehydration, polycythaemia, thrombocythaemia, some oral contraceptive pills, protein C or S deficiency or antithrombin III deficiency, or vessel occlusion by tumour or abscess. Cerebral infarction may also result from sustained systemic hypotension from any cause, particularly if associated with hypoxaemia.

BLOOD TESTS

Haemoglobin, white cell count and platelets are determined to look for polycythaemia, infection or thrombocythaemia. A raised erythrocyte sedimentation rate or C-reactive protein level may indicate vasculitis, infection or carcinoma, warranting further appropriate investigations.

Coagulation screen should be taken together with serum cholesterol, triglyceride and syphilis serology. Specific investigation for thrombophilia due to protein C, protein S, Leiden factor V and antithrombin III abnormalities should be undertaken in patients with venous thrombosis or patients with otherwise unexplained cerebral infarction or TIA.

ELECTROCARDIOGRAPHY

This may demonstrate atrial fibrillation or other arrhythmia, or recent myocardial infarct.

ECHOCARDIOGRAPHY

Either transthoracic or transoesophageal echocardiography (TOE) may demonstrate mural or atrial appendage thrombus as a source of embolism. TOE is more effective in detecting patent foramen ovale, aortic arteriosclerosis or dissection.

COMPUTED TOMOGRAPHY (CT) OR MAGNETIC RESONANCE IMAGING (MRI) SCANNING

These techniques are used to distinguish infarction from haemorrhage. Tumour, abscess or subdural haematoma may also produce the symptoms and signs of stroke. Ideally, the scans should be undertaken as soon as possible to exclude conditions that are treatable by neurosurgery. Early scanning is vital if interventional treatment such as thrombolysis, anticoagulation, antiplatelet therapy or surgery is planned.

The CT scan may be normal or show only minor loss of grey/white matter differentiation in the first 24 hours after ischaemic stroke but haemorrhage is seen as areas of increased attenuation within minutes. After a couple of weeks the CT appearances of an infarct or haemorrhage become very similar and it may be impossible to distinguish them if CT is delayed beyond this time. CT angiography will often demonstrate vascular abnormalities and vasospasm but multimodal MRI, a combination of diffusion and perfusion-weighted MRI and MR angiography (MRA), is much more sensitive in demonstrating small areas of ischaemia and targeting those patients most suitable for thrombolysis.⁵ Where cerebral infarction has occurred as a result of venous thrombosis, the best imaging technique is MRA. Other imaging techniques are appropriate to identify the source of stroke in specific areas. Any patient with a stroke or TIA in the internal carotid artery territory should have duplex Doppler ultrasonography which may demonstrate stenosis, occlusion or dissection of the internal carotid. Where trauma is an aetiological factor reconstruction CT bone window views.

AIRWAY AND BREATHING

Patients with Glasgow Coma Scores (GCS) of 8 or less or those with absent gag will require intubation to preserve their airway and prevent aspiration. Where this requirement is likely to be prolonged, early tracheostomy should be considered. Adequate oxygenation and ventilation should be confirmed by arterial blood gas analysis, and supplemental oxygen prescribed if there is any evidence of hypoxia. If hypercarbia occurs then ventilatory support to achieve normocarbia is necessary to prevent exacerbation of cerebral oedema. Ventilatory support in such cases has been shown to result in improved prognosis.⁷

CIRCULATORY SUPPORT

A large number of stroke patients will have raised blood pressure on admission, presumably as an attempt by the vasomotor centre to improve cerebral perfusion. Hypertensive patients may have impaired autoregulation and regional cerebral perfusion may be very dependent on blood pressure.⁸ The patient’s clinical condition and neurological status should determine treatment rather than an arbitrary level of blood pressure. Control of even very high blood pressure (220/120 mmHg; 29.3/16.0 kPa) is not without risk and may result in progression of ischaemic stroke, so reduction should be monitored closely.⁹ It would seem reasonable on physiological grounds to avoid drugs that cause cerebral vasodilatation in that they may aggravate cerebral oedema, although there is no hard evidence for this. Animal experiments have suggested that haemodilution could improve blood flow by reducing whole blood viscosity but a recent multicentre study has failed to identify any clinical benefit.¹⁰ Cardiac output should be maintained and any underlying cardiac pathology such as failure, infarction and atrial fibrillation treated appropriately.

METABOLIC SUPPORT

Both hypo- and hyperglycaemia have been shown to worsen prognosis after acute stroke, therefore blood sugar levels should be maintained in the normal range.¹¹ In the long term, nutritional support must not be neglected and early enteral feeding instituted by nasogastric intubation. In the longer term, particularly where bulbar function is reduced, percutaneous endoscopic gastrostomy is necessary.

ANTICOAGULATION

In theory, the use of anticoagulation reduces the propagation of thrombus and should prevent further embolism. In practice, the reduction in risk of further thromboembolic stroke is offset by a similar number of patients dying from cerebral or systemic haemorrhage as a result of anticoagulation.^12,13 Anticoagulation can only be recommended in individuals where there is a high risk of recurrence, such as in those patients with prosthetic heart valves, atrial fibrillation with thrombus or those with thrombophilic disorders. A CT scan must be obtained prior to commencing therapy to exclude haemorrhage, and careful monitoring used. In patients with large infarcts there is always the risk of haemorrhage (haemorrhagic conversion) into the infarct and early heparinisation is best avoided.

THROMBOLYSIS

Systemic thrombolysis with streptokinase carries a very high risk of cerebral haemorrhage and should not be used.¹⁴ There is some evidence that intravenous recombinant tissue plasminogen activator (alteplase) has a better safety/efficacy profile. The National Institute of Neurological Disorders and Stroke (NINDS) trial showed a significant improvement in those patients given alteplase rather than placebo within 3 hours of acute stroke.¹⁵ This benefit was not found to be statistically significant in two European trials^16,17 and the ATLANTIS trial showed no significant benefit at 90 days in the alteplase group together with an increased risk of intracranial haemorrhage.¹⁸ The 2006 Cochrane Library database states that thrombolysis appears to result in a significant net reduction in the proportion of patients dead or dependent in activities of daily living. However, there appears to be an increase in deaths within the first 7–10 days, symptomatic intracranial haemorrhage and deaths at follow-up at 3–6 months. The data from trials using intravenous recombinant tissue plasminogen activator, from which there is the most evidence on thrombolytic therapy so far, suggest that it may be associated with less hazard and more benefit. There is heterogeneity between the published trials for some outcomes so that the optimum criteria to identify patients most likely to benefit and least likely to be harmed, the latest time window, the agent, dose and route of administration are all unclear. Nevertheless, the data are promising and may justify the use of thrombolytic therapy with intravenous recombinant tissue plasminogen activator in experienced centres in highly selected patients where a licence exists. However, the data do not support the widespread use of thrombolytic therapy in routine clinical practice at this time, but suggest that further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which it may best be given.¹⁹

CEREBRAL PROTECTION

Various agents such as free-radical scavengers, calcium antagonists, magnesium, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists, glutamate antagonists and γ-aminobutyric acid antagonists have been used in attempts to limit the deleterious effects of the biochemical changes that occur intracellularly following ischaemia. No agent has been shown to be effective in placebo-controlled phase III trials.

DECOMPRESSIVE CRANIOTOMY

This is an option in young patients with large middle cerebral artery territory infarcts in the non-dominant hemisphere. Untreated, these normally have a mortality of 80% and it is suggested that this procedure can reduce mortality to around 30%, but with residual neurological deficit. This procedure is limited to specialist centres. Other forms of surgical intervention proven to be effective in making more intracranial space and reducing intracranial pressure are drainage of secondary hydrocephalus by extraventricular drain (EVD) insertion or evacuation of haemorrhage into infarcted areas, resulting in new compressive symptoms. This is especially useful in the posterior fossa where the room for expansion of mass lesions is limited by its anatomy.