What is the most likely cause? What other possibilities should you consider?

What are the important features of the examination and ancillary history?

What investigations would you order?

Apart from a blood sugar of 9.6 mmol/L and evidence of left ventricular hypertrophy on ECG, her blood tests and ECG are unremarkable. Other investigations are shown in Figure 44.1–3.

Figure 44.1 Hyperacute CT scan.

Figure 44.2

Figure 44.3 A CT angiogram.

What do the CT and CTA show? It is now 2 hours and 50 minutes post stroke onset. How would you proceed?

What in-hospital care should this patient receive and what further investigations should be performed?

What are some possible complications which may arise in the subacute stage?

What chronic treatment should this patient receive?

A.1 It is most likely that this patient has had a stroke. Other causes of a rapidly progressive focal neurological deficit include migraine with aura, epilepsy with a post-ictal Todd’s paresis, a conversion disorder and hypoglycaemia, although the lack of observed ictal activity and the sudden onset of symptoms would make acute stroke the most likely cause. This is an emergency – ‘Time is brain’, and you need to work swiftly in order to provide the best therapy.

A.2 The acute evaluation of a patient with a presumed stroke is guided by the need to determine, as quickly as possible:

Other features which are important to establish, but which should not slow a decision regarding the institution of thrombolysis, include:

Any observed ictal activity should raise the possibility of a Todd’s paresis (although seizures can also occur at acute stroke onset). A history of intracerebral haemorrhage, recent major trauma, surgery or bleeding, recent myocardial infarction or recent ischaemic stroke should be determined, as these may contraindicate thrombolysis.

Vital signs should be noted. Elevated blood pressure is common post stroke and persistently elevated blood pressure (>185/110) may contraindicate thrombolysis. A fever may suggest an underlying cause, such as bacterial endocarditis. Note should be taken of pulse irregularity (atrial fibrillation is an important cause of stroke).

A directed neurological examination should be performed. Depressed conscious state suggests brainstem ischaemia or bihemispheric emboli. A gaze preference to one side suggests an ipsilateral frontal lobe or contralateral pontine stroke. Dysconjugate gaze suggests vertebrobasilar disease, as does vertical or horizontal nystagmus. Visual fields should be assessed. The presence of a dysphasia or dysarthria should be noted. Facial and limb strength should be tested, as should facial and limb sensation. Crossed or bilateral deficits suggest brainstem disease. The presence of ataxia should be noted. In the setting of preserved sensation and vision, evidence of inattention may be found (a failure to perceive bilateral simultaneous stimuli).

Underlying cardiovascular risk factors should be established, and a general examination performed.

A.3 The two most important investigations are a blood sugar level and a CT (preferably CT angiogram). CT perfusion studies are also increasingly used, as they help distinguish stroke core (dead tissue) from penumbra (salvageable tissue). Hypoglycaemia can mimic acute stroke, and hyperglycaemia is a contraindication to thrombolysis. The CT scan determines whether the acute stroke is haemorrhagic or ischaemic. Unless the patient is also on warfarin (an elevated INR contraindicates thrombolysis), these two tests provide sufficient results to proceed with thrombolysis.

Other investigations which should be obtained at this stage include a full blood examination and serum electrolytes (a low haemoglobin may suggest occult bleeding and a platelet count below 100 × 10⁶/L contraindicates tPA). An ECG should be performed to look for previous silent myocardial ischaemia and atrial fibrillation (both potential stroke causes).

A.4 The CT scan is normal, except for a linear hyperdensity in the region of the right middle cerebral artery (see Figure 44.1) (the so-called ‘string sign’), and subtle blurring of grey–white differentiation of the medial lentiform nucleus (see Figure 44.2). The CTA demonstrated occlusion of the proximal MCA (not shown) and, more superiorly, significant hypoperfusion of the entire right MCA territory (see Figure 44.3). These findings are consistent with ischaemic stroke. Plain CT is insensitive for cerebral ischaemia in the acute phase, but hypoperfused and infarcted areas can be demonstrated with CT angiography and perfusion imaging. Extensive areas of CT hypodensity represent already infarcted tissue; thrombolysis in this setting is unlikely to be effective, and is more likely to cause haemorrhagic transformation of the infarcted area.

The benefit from thrombolysis with alteplase within hours of stroke onset has recently been confirmed in multicentre trials. She should receive the accepted dose (0.9 mg/kg over an hour with the first 10% as a bolus).

Her blood pressure should not be lowered, as this may decrease perfusion to the threatened, hypoperfused brain (the ‘ischaemic penumbra’). Aspirin should not be administered acutely until 24 hours post-tPA. Conversely, ischaemic stroke patients not receiving tPA should receive aspirin at admission; aspirin treatment leads to both short- and long-term reductions in recurrent stroke, death and disability.

A.5

A.6 Patients’ neurological status may deteriorate in the subacute setting due to several reasons, including:

Progressive neurological deterioration in the setting of a large anterior circulation stroke has a mortality rate, untreated, of around 80%. This figure can be significantly reduced (in patients less than 60 years of age) by decompressive craniotomy. Some patients who would have died will make an excellent recovery, although some additional patients will survive, but with a severe neurological deficit.

Stroke patients are also prone to develop infections, including aspiration pneumonia, urinary tract infections and pressure sores. The chances of these occurring may be lessened by screening patients for dysphagia, avoiding catheterization and appropriate bedding/turning.

Post-stroke fever is common, and is linked to worse outcome. Although not of proven benefit, administration of antipyretics is recommended in this setting. Patients with stroke, particularly those with decreased mobility, are at increased risk of deep venous thrombosis and pulmonary embolism. This risk can be lessened by antithrombotics, compression stockings, avoidance of dehydration and early mobilization. Malnourishment is a common complication. Post-stroke depression is extremely common, undertreated, and possibly preventable by prophylactic antidepressant therapy.

A.7 The likely aetiology of this patient’s stroke is cardioembolism from atrial fibrillation. Her risk of recurrent stroke (untreated) is around 10% per year: this can be reduced to around 3% with warfarin (as opposed to 8% with aspirin). Warfarin is also significantly better in this setting than a combination of aspirin and clopidogrel. It is uncertain in this setting when warfarin should be commenced, as the benefit of early treatment (prevention of further emboli) may be more than offset by the risk of symptomatic haemorrhagic transformation. Most doctors would commence treatment at some point between 10–14 days post stroke (depending on infarct volume).

She may benefit from both more intense lipid-lowering therapy and more intense antihypertensive therapy. Lipid-lowering goals post stroke are uncertain, although a significantly lower risk of stroke was seen in non-hypercholesterolaemic patients following 80 mg/day of atorvastatin versus placebo. However, cardioembolic stroke patients were excluded from this trial. Likewise, in the PROGRESS trial, a combination of perindopril and indapamide was beneficial in stroke prevention, but it is unclear whether this benefit applies to patients already on multiple agents who have already met blood pressure goals. The benefit of lowering her HBA1c levels below 7.8% for stroke prevention is likewise uncertain.

Stroke is the second most common cause of death and disability worldwide. While stroke is more common with increasing age, 20% of strokes occur in patients aged less than 60.

Ischaemic stroke is the commonest form of stroke. Other causes include intracerebral haemorrhage and subarachnoid haemorrhage. Cardioembolism, large artery thromboembolism and small vessel disease are the main aetiological subtypes of ischaemic stroke. Hypertension, advancing age, previous stroke or transient ischaemic attack (TIA), smoking, atrial fibrillation and diabetes mellitus are the most potent risk factors. Hypertension is the most important. The epidemiological relationship between stroke and hypercholesterolaemia is weak, but statin therapy in hypercholesterolaemic patients clearly lowers stroke risk.

Acute stroke is a medical emergency, as is a TIA (10% of TIA patients will have a stroke within a month, most within 2 days). Thrombolysis within 4.5 hours of stroke onset improves outcome when administered to patients without contraindications. Earlier treatment leads to increased chances of benefit. For an outcome of complete or almost complete recovery, the number needed to treat is around eight for treatment within 3 hours and 12 for between 3 and 4.5 hours. Thrombolysis carries a small risk of symptomatic haemorrhagic transformation (2–7%, depending on definition used).

Level 1 evidence supports the following acute interventions in ischaemic stroke:

Patients with minimal or no neurological deficit and ipsilateral carotid atherosclerosis (>70%, and perhaps greater than 50% in males) should be treated by endarterectomy as soon as possible to prevent further strokes. It is not yet proven whether stenting is equivalent to an open procedure.

Other proven secondary prevention interventions include:

Smoking cessation, moderation or cessation of heavy alcohol intake, dietary modification (e.g. a ‘Mediterranean’ diet) and aerobic exercise are all likely to reduce the risk of recurrent stroke.