Stroke

Published on 12/04/2015 by admin

Last modified 22/04/2025

Print this page

This article have been viewed 1405 times

14 Stroke

Introduction

All too often a patient presents to hospital saying ‘I thought I was having a stroke but wanted to wait to see what happened’. If not the patient, then the relative or spouse says something similar. This wouldn’t happen with a suspected ‘heart attack’!

It is sobering to acknowledge that one can replace a heart, or part of a heart, but it is still impossible to replace the ‘motherboard’ in the brain. The heart is basically a pump for which one can even offer a mechanical substitute. Conversely, the brain is a super computer that is still not fully understood. It is time to replace the nihilism and think in terms of ‘brain attack’, in much the same way one thinks of ‘heart attack’. To do this underlines the most important message for either heart or brain, namely, ‘Time is of the essence!’ The catchcry for people dealing with stroke is ‘Time is brain’.

What follows is an overview of stroke that offers a clinician’s perspective of management. No message is more important than the need for early presentation. The previously accepted three-hour time window has been expanded to four-and-a-half hours in which to safely offer intravenous tissue-type plasminogen activator (tPA),¹ but sooner is still better.

Atherosclerosis

‘Brain attacks’ and ‘heart attacks’ have a common pathophysiology. An embolus of thrombus dislodges from the surface of an atherosclerotic plaque and becomes lodged downstream to occlude blood flow and hence nutrition distal to the blockage. This accounts for ischaemic strokes, comprising 85% of all strokes (only 15% have haemorrhagic aetiology).²

Atherosclerosis increases with age, hypertension, hyperlipidemia, diabetes and cigarette smoking.² It follows that medical management must address these factors. The thrombus that is dislodged from the plaque was formed consequent to prothrombotic effects involving tissue factor. Activated factor VII with platelet recruitment results in formation of platelet-rich fibrin thrombus, which embolised. Thus antiplatelet agents are important in preventing thrombotic emboli and hence strokes.

Cardiac causes

One of the most common cardiac causes of strokes is atrial fibrillation (AF). It also occurs with rheumatic heart disease, increasing age, hypertension, ischaemia and thyroid disease. AF occurs in approximately 1% of those under 60 years and about 6% in those over 80 years, and the population is ageing.

While there has been an attempt to classify AF into acute and chronic,³ this concept has less relevance to the neurologist/stroke-ologist, whose most important take-home-message concerning AF is the need to prevent emboli. Hence, one must recognise the need for anticoagulation. The actual treatment of AF is supervised by the cardiologist, but anticoagulation with Coumadin® is a high priority for stroke prevention. More recently a new class of anticoagulation drug has emerged.⁴ It is still too early to be certain about the place of dabigatran, but it appears destined to replace Coumadin® as the drug of choice for patients with AF. This remains a question for consultants until there is wider experience.

There are other cardiac causes of emboli, such as micotic emboli, with growths particularly on rheumatic valves. Unless this is appreciated with an index of suspicion for bacterial endocarditis, it may be overlooked. Mercifully this is rare but echocardiography is mandatory in the stroke evaluation. Transoesophageal echocardiogram is preferable, especially in the young stroke patient. Another cause detected by echocardiogram is patent foramen ovale (PFO), which may be under-diagnosed in stroke patients. One study reported in excess of 15% in over 55-year-old cryptogenic stroke patients having PFO with atrial septal aneurysm.⁵ The question of closure of PFOs in stroke patients or those with transient ischaemic attacks (TIAs) is a topic of some debate, which is not yet fully resolved. Evidence suggests an association of PFO with hypercoagulation, especially factor V leiden and prothrombin G20210A genetic mutations.⁶ Often hypercoagulable states travel together to evoke symptoms, such as dehydration or antiphospholipid antibodies in association with prothrombin G20210A mutations. The take-home-message is that the stroke patient deserves a detailed assessment of their hypercoagulable profile. This should have been done while in hospital, but the general practitioner can check to make sure.

Cardiac consideration is not restricted to stroke prevention but also offers a window to predict post-stroke mortality. Conventional heart rate variability measures were not of prognostic value, but abnormal long-term heart rate dynamics do predict post-stroke mortality. They may have value in risk stratification in stroke.⁷

Carotid artery disease

Carotid vessels are a major alternative source of emboli, but management of carotid disease relies on antiplatelet agents rather than full anticoagulation (if surgery is not warranted).

The North American Symptomatic Carotid Endarterectomy Trial (NASCET)⁸ found that stroke was reduced by 17% where carotid stenosis exceeded 70%, hence becoming the benchmark for ordering endarterectomy. Some advocate surgical intervention with stenosis as low as 60%, even in asymptomatic patients.⁹ Personal preference favours the higher figure.

Stenting is a viable alternative for cardiac vasculopathy and is becoming a respected alternative to carotid endarterectomy.¹⁰ Its exact place remains undefined with growing popularity. Furlan¹¹ reviewed the SAPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial, which showed that carotid artery stenting was safer than carotid endarterectomy in patients at high surgical risk, because of lower risk of myocardial infarction within 30 days after carotid stenting when compared to surgery. Furlan¹¹ reviewed the EVA-35 Study (Endarterectomy versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis in the same issue of The New England Journal of Medicine), which concluded that stenting was more risky than endarterectomy for 30-day incidence of stroke or death. Carotid endarterectomy is also considered a safer option than is stenting in the elderly.¹²

This underpins the need to investigate for carotid stenosis with tools such as duplex Doppler, CTA or MRA or a combination thereof to decide upon appropriate intervention. The general practitioner may initiate both Doppler studies and CTA—and may bypass the neurologist by referring to the vascular surgeon—although most often will rely on a team, including both neurologist and surgeon.

Hyperlipidemia

The meta-analysis of 90 000 patients from studies assessing the benefits of statins in stroke prevention demonstrated that the reduced risk of stroke was particularly reflected in the lowering of low-density lipoprotein cholesterol levels.¹³ Statins have become a basic component of stroke management.

The recent SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial of 4731 stroke or TIA patients concluded that 80 mg of atorvastatin per day reduced the overall incidence of stroke and cardiovascular events. It was associated with an increased incidence of haemorrhagic stroke.¹⁴ Personal preference favours starting with a lower dosage of statin and titrating to effect by monitoring cholesterol profile.

Transient ischaemic attacks (TIAs)

Perhaps the best way to consider TIAs is to equate them with mini strokes that resolve within a day. There is an even more worrying attitude to TIAs than there is to stroke. Because it has resolved by day’s end and very often much sooner, the attitude to TIA is complacent. A recent study confirmed that hospital admissions of TIA patients to a specialised stroke unit has beneficial effect on short-term outcome,¹⁵ and is preferable to home management and nihilism. Reliance on the ABCD² score does not necessarily increase protection by the theoretical admission of TIAs at greater risk^16,¹⁷ (see Table 14.1).

TABLE 14.1 ABCD ² scores

Characteristic	Points
A—Age ≥ 60 years	1
B—Blood pressure > 140/90 mmHg at presentation	1
C—Clinical features:• unilateral• speech impairment without weakness	21
D—Duration:• > 60 minutes• 10–59 minutes	21
D—Diabetes	1
2 × Day stroke risk:• low score (< 4) = 1.0%• moderate score (4–5) = 4.1%• high score (6–7) = 8.1%

This reinforces that stroke and TIA should not be taken lightly—they demand referral to a hospital as a matter of urgency. TIA is a warning of an impending more significant ‘brain attack’ and should be treated with respect. TIA mimics, including syncope, seizure, migraine, vertigo and its causes, encephalopathy of non-vascular origin, multiple sclerosis or even transient global amnesia, may confound the picture. It remains far safer, where doubt exists, to have these assessed in hospital rather than expose the patient to risk of stroke. Many of the mimics are themselves worthy of admission, and there should be no shame in referring them to hospital for assessment.¹⁸

Diagnosis of stroke

Correct diagnosis pre-empts appropriate treatment and, while an established stroke is easily diagnosed, the section on TIA highlights the scope of differential diagnoses. The pathophysiology and anatomical site defines the stroke’s expression, be it motor or sensory deficit, loss of eloquent functions of speech, number manipulation, comprehension, orientation, consciousness or more subtle effects determined by smaller lesions.

The mnemonic ‘FAST’ remains a valuable tool for the general practitioner (see Table 14.2) and may be the start of the diagnostic approaches. The Cincinnati Pre-hospital Stroke Scale (CPSS) was developed to help recognise strokes. It has since been modified to produce the ‘Sudden Symptoms’ and ‘FAST’ mnemonic to assist with early stroke recognition (see Table 14.2). Kleindorder et al¹⁹ found that ‘Suddens’ would fail to detect 0.1% of strokes and ‘FAST’ would miss 11.1%.

TABLE 14.2 ’Sudden Symptoms’ and ‘FAST’ mnemonic for stroke detection

Sudden symptoms	FAST
Stroke patients may have sudden onset of: • weakness or numbness on one side • difficulty speaking or understanding • trouble seeing in one or both eyes • ’dizziness’ or difficulty walking • severe headache of unknown cause

Ask patients to:

• smile,

• raise both arms and

• repeat phrase

F = Face—uneven movement A = Arm—one side drifts S = Speech—sounds strange T = Time—go to hospital ASAP

One cannot over emphasise the need for early intervention should tPA for thrombolysis be appropriate. Rapid referral to a hospital capable of providing such intervention is mandatory. Before tPA can be given, within the critical four-and-a-half hour window, there must be cerebral imaging to exclude intracerebral haemorrhage, as haemorrhage and tPA are incompatible. Use of tPA is becoming more widely available and it may assist the general practitioner to understand some of the inclusion or exclusion criteria for its use (see Table 14.3). Early referral is enhanced by appreciating the process necessary to be completed by administration of tPA. Intra-arterial thrombolysis is also a valid form of intervention but it is only available in hospitals with access to interventional radiology, which restricts it to tertiary referral hospitals. This too is important for the family doctor to appreciate, as it may determine which in a selection of hospitals should be the preferred place of referral. The availability of a stroke unit is also an important deciding factor as over the last fifteen years they have been shown to improve prognosis.²⁰

TABLE 14.3 Criteria for use of tPA for acute stroke

Inclusion	Exclusion
Ischaemic stroke causing definable neurological deficit	Resolution or clearing or improving of neurological deficits
CT imaging excluding haemorrhage	CT evidence of widespread or large infarction (e.g. hypodensity > cerebral hemisphere)
Presentation and CT imaging available within 4.5 hours	INR > 1.7
Informed consent	Given heparin in previous 48 hours with prolonged PTT
	Platelets < 100 E9/L
	Hypertension: • systolic > 185 mmHg • diastolic > 110 mmHg or needing aggressive BP intervention
	Previous stroke or head injury within 3 months
	Major surgery within 2 weeks
	Symptoms suggestive of subarachnoid haemorrhage
	GI or UT bleed within 3 weeks

Lifestyle issues

Family physicians play an absolutely fundamental and pivotal role in stroke management. As has already been demonstrated, stroke and lifestyle issues are inseparable. Risk factors, such as hypertension, AF, hyperlipidemia, diabetes, cigarette smoking, excessive consumption of alcohol, dieting indiscretions, past history of stroke or vasculopathy, lack of exercise and overall disrespect of personal health, plus non-compliance with existing advice to curtail these activities and to take medications, are just as important as sophisticated intra-hospital intervention (see Table 14.4).

TABLE 14.4 Risk factors for stroke

Non-modifiable	Modifiable
Age	Prior stroke or TIA resulting in secondary stroke prevention—compliance
Gender	Hypertension
Race or ethnicity	Diabetes
Family history	Hyperlipidaemia
	Atrial fibrillation (AF)
	Homocysteinaemia
	Carotid stenosis
	Smoking
	Excess alcohol
	Obesity
	Lack of exercise

Addressing these lifestyle issues has far greater potential to reduce stroke rate than does anything that can be added by consultants. Failure to respect these factors renders most of the other forms of intervention suboptimal. One cannot over emphasise these when evaluating stroke treatment. Proper attention to them could obviate the need for more aggressive therapies.

Patient assessment

Once the patient arrives in hospital, the initial assessment must determine that ever-important timeframe. Should a patient wake from sleep with stroke symptoms or signs then it is impossible to determine the timeframe during sleep, and IV tPA thrombolysis is usually contraindicated. Some advocate taking the midpoint of sleep duration as the commencement of the ‘ticking clock’, but this seems unsatisfactory.

Should the timeframe permit, non-contrast enhanced CT will allow exclusion of intracerebral bleed. Should this show a very large stroke then risk of haemorrhagic transformation also causes exclusion (see Table 14.3).

Depending on the patient’s age and circumstances, blood samples should be taken for thrombophilic screening, including: ANA; ENA; cardiolipin antibodies; homocysteine; AdsDNA; lupus inhibitor; B₁₂, folate; ESR; CRP; full blood count; biochemical screen; blood sugar level (and if indicated HbA1c); T3, T4 and TSH; ACE; antithrombin III; factor V leiden; protein C and S; infective causes (such as serology for syphilis and HIV); and possibly even the prothrombin G20210A mutation.

Magnetic resonance imaging (MRI) with MRA (angiogram) of brain provides extra information, especially diffusion-weighted sequences, which differentiate newly acquired infarcts from longer established lesions. Inconsistency between perfusion and diffusion imaging (be it via CT or MR) defines the penumbra (the tissue not yet necrotic from the stroke), which surrounds the non-recoverable tissue. This indicates the potential benefit from throbolysis. This is clearly the domain of the specialist.

Carotid duplex Doppler and cardiac echocardiogram have already been discussed as important tools to discern the source of cerebral emboli.

Medical treatment of stroke

a Antiplatelet agents

There have been a multitude of trials designed to ascertain which antiplatelet agent or combination of agents is superior. Each has had the mandatory anagram such as: ESPS 1 and 2—European Stroke Prevention Study (J Neurol Sci 1996, 143:1–13); CAPRIE— Clopidogrel v Aspirin in Patients at Risk of Ischaemic Events (Lancet 1996; 348:1329–1339); CURE—Clopidogrel in Unstable Angina to Prevent Recurrent Episodes (N Engl J Med 2001, 345:494–502); MATCH—Management of Athero-Thrombosis with Clopidogrel in High-risk Patients (Lancet 2004, 364:331–337); CHARISMA—Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilisation, Management and Avoidance (N Engl J Med 2006, 354:1706–1717) or ESPRIT—European/Australasian Stroke Prevention in Reversible Ischaemia Trial (Lancet 2006, 367:1665–1673).

The number of therapeutic trials regarding antiplatelet agents has expanded exponentially: ROCKET—Roxifiban Oral Compound Kinetics Evaluation Trial 1 (ROCKET—1 Platelet Substudy) Effect of roxifiban on platelet aggregation (Am Heart J 2003, 146:91–98); PRoFESS—Prevention Regimen for Effectively Avoiding Secondary Strokes: aspirin plus extended release dipyridamole versus clopidogrel and telmisartan (Lancet Neurol 2008, 7(10):875—884); ATHENA–A Placebo-controlled, Double-blind, Parallel-arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalisation or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter: the inefficacy of dronedarone in AF (Circulation 2009, 120:1174–1180); ARISTOTLE—Apixaban for Reduction In Stroke and Other ThromboembLic Events in Atrial Fibrillation: efficacy of apixaban in AF (Am Heart J 2010, 159:331–339); and AVERROES—Apixaban Versus acetylsalicylic acid to prevent stROke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment: efficacy of apixaban versus aspirin in AF (Am Heart J 2010, 159:348–353).

These suggest extended release dipyridamole in combination with aspirin (Asasantin® SR 200/25 1 b.d.) is the antiplatelet agent of choice for stroke prevention. The combination of aspirin and clopidogrel has an increased risk of intracerebral bleeds, but is favoured by cardiologists for cardiovascular disease and peripheral vascular disease. Aspirin is more effective than clopidogrel alone in stroke prevention, but clopidogrel alone is favoured for patients who are aspirin intolerant.

As already stated, Coumadin® is preferred when the emboli are of cardiac origin, at least until we fully appreciate the exact position of dabigatran ⁴ in our treatment algorithm.

b Statins

Statins, such as pravastatin ²¹ and atorvastatin,^22,²³ have long been advocated to reduce strokes. As already discussed, doses of 80 mg of atorvastatin may be advocated¹⁴ but personal preference is to start low at 10–20 mg nocte and titrate to LDL level. Statins also help stabilise vessel wall integrity, so enhancing stroke prevention. They have proven to be safe and effective agents in stroke prevention.²⁴

c Antihypertensives

The HOPE (Heart Outcome Prevention Evaluation) study was designed to look at antihypertensives in management of cardiovascular disease using ramipril.²⁵ It was followed by closer examination of use of ramipril in stroke prevention.²⁶ The combined studies entrenched the use of angiotensin converting enzyme inhibitors (ACE inhibitors), particularly ramipril (building up to 10 mg per day), in stroke management. Use of ACE inhibitors was further reinforced with PROGRESS (Perindopril Protection Against Recurrent Stroke Study), which showed that perindopril was also effective in stroke prevention.²⁷

Following the recognition of the benefits of ACE inhibitors in stroke management, use of angiotensin II receptor blockade was also explored ²⁸ and hypertension management has become fundamental for stroke.²⁹ While various pharmaceutical companies espouse the virtue of their particular antihypertensive agent, the most important take-home-message is to tackle hypertension as a major focus in stroke prevention.