Stroke

1. Stroke

2. Introduction • Stroke is a clinical syndrome of sudden focal or global cerebral dysfunction lasting more than 24 hours, of presumed vascular origin. It may occur as a result of cerebral infarction (ischaemic stroke), intracerebral haemorrhage or subarachnoid haemorrhage. Ischaemic stroke is the commonest type, accounting for about 85%.

3. Pathophysiology of ischaemic stroke • Thrombo-embolic occlusion of blood flow triggers a sequence of events, the ischaemic cascade. Failure of energy production leads to anaerobic glycolysis and lactic acidosis, and failure of the ion pumps results in neuronal depolarisation and intracellular calcium overload. These events lead to the release of neurotoxic substances such as excitatory neurotransmitters (chiefly glutamate), inflammatory mediators (eg. prostaglandins, leukotrienes), toxic free radicals (eg. nitric oxide) and activated lytic enzymes (lipases, proteases), ultimately causing neuronal death (1). • Ischaemic damage depends on the degree and the duration of ischaemia. Following complete occlusion of a vessel, a central core of densely ischaemic tissue is irreversibly damaged (infarction) within minutes.

4. Around the infarction is an area of critical ischaemia (ischaemic penumbra), which is inadequately perfused. • Neurones in the penumbra are energy deficient and electrically quiescent, but have intact ion pumps and are viable. Prolonged ischaemia will lead to their death and extension of the infarct. If perfusion is restored within a certain period of time, neurones in the penumbra can be salvaged; this constitutes a therapeutic window of opportunity. In humans, this window period is believed to be 3 to 6 hours. • Early treatment • Components of the early treatment of ischaemic stroke are shown in Box 1.

5. Box 1. Early treatment of ischaemic stroke 1. General care 2. Specific treatment: thrombolysis, anticoagulants, antiplatelet agents and neuro-protective agents 3. Emergency approach 4. Stroke unit care 5. Treatment of complications 6. Treatment of co-morbidity 7. Rehabilitation 1. General care

6. 1. General care General care of a stroke patient in the early stages aims at sustaining life (eg. airway, breathing, circulation) and maintaining vital bodily functions (eg. fluid and electrolyte balance, blood glucose, nutrition, swallowing, temperature, and bladder, bowel and skin care). Autoregulation of regional cerebral blood flow is defective in the ischaemic penumbra, and blood flow is dependent on cerebral perfusion pressure. Volume depletion or a fall in blood pressure will reduce perfusion pressure and lead to extension of the infarct (2,3). Attention to fluid and electrolyte balance is essential. Volume overload can lead to cerebral oedema, and volume depletion with accompanying hypotension and electrolyte disturbances can adversely affect outcome. Volume replacement should be by the oral route, or a nasogastric tube when swallowing is impaired. Intravenous fluids when required should be given as isotonic saline. Aspiration is a concern in the early stages, as swallowing difficulties are common. A simple bedside test of swallowing is to give 1 or 2 teaspoonfuls of water with the patient seated; coughing or `developing a wet voice' indicates impaired swallowing and oral feeding should not be attempted.

7. Blood pressure management is critical after a stroke. A transient rise in blood pressure is seen in up to 80% of patients. This resolves spontaneously in most cases by 7 to 10 days. Injudicious treatment of reflex elevation in blood pressure may lead to a fall in perfusion pressure in the penumbra. Treatment should be started only when definite indications (Box 2) are present (2,3,4). In their absence blood pressure should be monitored regularly but treatment withheld for 10 days. Antihypertensive therapy is commenced if blood pressure remains persistently elevated after 10 days. • Blood pressure reduction should be gradual, with a targeted reduction of about 10 to 15% over 24 hours. Reducing blood pressure to below systolic <180, diastolic <110 mmHg can be harmful (3,4). Short acting oral agents (eg. captopril) are particularly useful.

8.  Box 2. Indications for early treatment of elevated blood pressure in acute stroke • Evidence of pre-existing hypertension •  documented previous hypertension - clinic records etc. evidence of hypertensive target organ •  damage, hypertensive retinopathy, left ventricular hypertrophy  on ECG •  Evidence of a hypertensive emergency eg. hypertensive encephalopathy, left heart failure. •  Blood pressure is very high: systolic >220-240, diastolic >120 mmHg

9. Blood glucose content is another critical determinant of outcome after stroke. Both hypoglycaemia and hyperglycaemia can be detrimental (4). Hypoglycaemia should be corrected with dextrose infusions. Hypergly-caemia is associated with aggravation of cerebral oedema and increased mortality, and needs treatment with insulin. Fever should be actively treated with antipyretics, and the cause, usually an infection, sought and treated. • Bladder dysfunction is common after a stroke, and both urinary retention and incontinence can occur. Urinary retention needs urethral catheterisation. In patients with urinary incontinence, residual bladder volume after micturition should be assessed by bladder ultrasound scan or by catherisation; an indwelling catheter is indicated where the residual volume is high, but others can be managed with external devices such as condom catheters

10. 2. Specific therapya) Thrombolysis • The success of thrombolytic therapy in acute myocardial infarction has rekindled interest in its use in stroke. Intravenous thrombolytic therapy has changed the treatment of acute ischaemic stroke. It appears that both the type of drug and the timing of administration are important determinants of outcome. Initial studies that used streptokinase did not show a definite benefit. However, the NINDS trial which used r-tPA within 3 hours of onset showed significant improvements in outcome (5). • The main complication of thrombolytic therapy is bleeding, which may be intracranial or extracranial. Spontaneous haemorrhagic transformation, a recognised complication of cerebral infarction, may be aggravated by thrombolytic therapy. Thrombolysis increases the severity of haemorrhage, rather than the incidence.

11. Early CT scans are useful not only to exclude haemorrhage before thrombolysis, but also to identify infarcts that may be at a higher risk of haemorrhagic transformation. The dose of r-tPA is 0.9 mg/kg up to a maximum of 90 mg, the first 10% as a bolus, and the balance as an infusion over 60 min. There are many contraindications for r-tPA including seizure at onset, pre-treatment BP systolic >185, diastolic>110 mm Hg, major infarct on CT scan, previous intracranial haemmorhage, recent myocardial infarct, recent or intended surgery, use of anticoagulant recently etc. IV r-tPA is now standard acute treatment in the USA, Australia and most European countries. Many concerns still remain largely owing to the risk of bleeding and the difficulties in initiating treatment within 3 hours (5). Intra-arterial thrombolysis using r-tPA has been shown to be beneficial in posterior circulation strokes due to basilar artery thrombosis. Its place in carotid territory strokes is under evaluation.

12. b) Anticoagulants • Anticoagulants are of two main types, and include parenteral heparin (unfractionated heparin and low molecular weight heparin _ LMWH) and oral warfarin. Oral warfarin is of proven benefit in prevention of stroke. Unfractionated heparin has been used in acute ischaemic stroke, especially in stroke-in-evolution or cardio-embolic stroke, without much evidence of benefit. Many recent studies have failed to demonstrate an improvement in outcome (7), and unfractionated heparin has no place in the management of acute ischaemic stroke. LMWH may be equally effective as unfractionated heparin, with a lower risk of bleeding. More large trials are necessary before they can be considered in routine clinical practice.

13. c) Antiplatelet agents • Aspirin and other antiplatelet agents are of proven value in primary and secondary prevention of stroke. Two large trials, each randomising about 20 000 patients, addressed the value of early use of aspirin in acute ischaemic stroke. Data from both trials have shown that early use of aspirin (160 to 300 mg within 48 hours) is beneficial in reducing deaths and dependency (7,8). The benefits appear to be mainly related to prevention of early recurrences. The place of other antiplatelet agents (such as dipyridamole, clopidogrel, ticlopidine and glycoprotein IIb/IIIa receptor antagonists) as acute treatment needs evaluation

14. d) Neuro-protective agents • Preserving the intergrity of the ischaemic neurones is important. Avoid factors that aggravate ischaemic damage; these include hypotension, hypoxia, hyperglycaemia and hyperpyrexia (1). Reducing the energy requirements of ischaemic neurones by high dose barbiturate therapy and hypothermia have shown promising results (1). Treatment with pharmacological agents that target specific events of the ischaemic cascade (neuro-protective agents) within the therapeutic window period is under evalution, and this may become first-line therapy in the future (4,9). Such agents include calcium channel blockers (eg nimopidine), GABA antagonists (eg clomethiazole), glutamate antagonists (eg eliprodil), free radical scavengers (eg tirilazad) and sodium channel blockers (eg lubeluzole).

15. 3.Treating stroke as an emergency • The main difficulty in using r-tPA and other potential therapies is the need to initiate treatment within 3 hours. Many countries have sucessfully overcome this challenge by developing public educational campaigns, emergency pre-hospital medical care systems with trained ambulance crews, rapid triage and 'fast-track' systems on admission to hospital, stroke units and stroke teams. Stroke is now treated as an emergency. • 4. Stroke units • A stroke unit is a multidisciplinary team of health care professionals, providing organised inpatient stroke care in a defined area. Compared with conventional care in a general medical ward setting, stroke unit care produces significant improvements in short term and long term outcome measures. Death, disability, dependency and hospital stay are reduced, and functional capacity is improved (10).

16. 5. Treatment of complications • Early detection and treatment of complications are essential to improve outcome after a stroke. Cerebral oedema, or brain swelling, is probably the most important early complication. Treatment of cerebral oedema should ideally be guided by intracranial pressure monitoring. In the absence of such facilities, patients with alteration of consciousness, large infarcts, and evidence of mass effect (midline shift, compression of ventricles) on CT scanning should be treated (Box 3). Other complications of stroke include haemorhagic transformation, seizures, respiratory and urinary infection, deep vein thrombosis and pulmonary embolism, acute peptic ulcer, pressure sores, neuropsychiatric sequelae such as anxiety or depression and musculo-skeletal sequelae such as contractures, spasticity and adhesive capsulitis of the shoulder.

17. Box 3. Management of raised intracranial pressure after stroke (3,4) • Elevate head end by 30° • Avoid or correct aggravating factors _ hypoxia, hyperglycaemia • Moderate fluid restriction • Avoid hypoosmolar fluids eg. dextrose • Giving osmotic agents (eg iv. mannitol) as indicated • Hyperventilation • IV barbiturates • NB. Steroids are of no value

18. 6. Treatment of co-morbidity • Patients with stroke are usually old and may have associated co-morbid conditions. These may interfere with the rehabilitation process (eg. chronic lung disease), or the treatment (eg. aspirin or warfarin in peptic ulcer disease), and need assessment and treatment in their own right. • 7. Rehabilitation • Rehabilitation is the process by which patients after a stroke are restored to their previous functional, mental and social capacity. This is best carried out by a multidisciplinary stroke team with the active participation of patients and care givers. • Conclusion • Stroke is an emergency, a 'brain attack'. Recent developments in drug therapy and service organisation have led to an aggressive approach to treatment of ischaemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Many new treatment modalities are being increasingly used, more are being developed and evaluated, and the future looks brighter for stroke patients. • The vascular diseases of cerebrum occupy one of the first places in the structure of organic pathology of the central nervous system (about 17%).

19. HAEMORRHAGIC STROKE • Haemorrhagic stroke develops as a result of involuntary break of intracerebral vessel and is accompanied by forming of haematoma. A intracerebral hemorrhage is one of the heaviest forms of vascular defeat of cerebrum. As a rule, a hemorrhage of brain develops as a result of hypertensive illness (50 — 60%), pathological changes in the vessels of brain, more frequent — after atherosclerosis. • Physical examination, births, emotional stresses, fluctuation in the temperature of body, alcoholic intoxication and others like that often predetermine the temporal increase of arterial pressure. A spontaneous hemorrhage of brain mainly occurred in women. In clinical practice hemorrhage is distinguished on lateral and medial simultaneously on both sides of internal capsule. A medial hemorrhage is often accompanied with penetration of haematoma in the cavity of lateral or III ventricle.

20. Clinic. Haemorrhagic stroke develops mainly sharply, often without some forecasters. A clinic is characterized by a sudden fainting fit and local neurological symptoms. Sometimes there is vomits. The face of patient becomes crimson-red, pulse tense, slow, breathings vowel, the temperature of body rises. A head and eyes is often returned aside. Another local symptoms are paresis or paralysis of extremities on a side opposite to the cell of hemorrhage, which arise up as a result of compression of the haematoma on formations of internal capsule or vessels. If a hemorrhage is comparative small, motive violations are poorly expressed, while a massive hemorrhage, squeezing an internal capsule, results in hemiplegia. • Exposure of other local symptoms, in particular violations of sensitiveness, hemianopsia, disorders of language, becomes possible after the exit of patient from the comatose state and renewal of consiousness. During short time from the moment of origin of stroke there are considerable vibrations of vegetative violations: a pallor of person changes by hyperemia or, opposite, he covered by sweat, the distal departments of extremities are cold, often all these phenomena prevail on the side of paralysis. In beginning of disease the increase of tone of muscles with violation of motive function is characteristic. • For diagnostics the most important method is computer tomografy. If at the persons of middle and young ages young the pressure of cerebrospinal liquid is frequently promoted, at the senile age people it can be normal or even reduced. The promoted maintenance of albumen is often exposed. On ЕЕG we can observed the М-еcho signal on opposite to hemorrhage site

21. Very frequent is horizontal large amplitude tonic nistagm which often unites with vertical, connected with asymmetrical position of eyes, «floating» eyeballs. Disorders of breathing appear in the case of heavy defeat of trunk. • Treatment. As lethality as a result of brain hemorrhage treated with conservative treatment is extraordinarily high, and in the case of surgical treatment goes down, that is why the necessary operation is a method of choice. • A lateral hemorrhage is an absolute testimony for surgical treatment. In the case of medial hemorrhage the prognosis for surgical treatment is worse. • In the case of penetration of blood in the ventricles of brain the conservative treatment is uneffective • Two types of operations are applied: 1) dissection of brain and delete of haematoma; 2) urgent punction of haematoma through a brain with sucking of blood. The cavity of haematoma once or twice is washed by isotonic solution of sodium chloride. • In the case of presence of blood clots in the cavity of ventricle washing is ineffective. • In the case of hemorrhage in a cerebellum haematoma is treated on the same principle, like the haematoma of large brain. • SHARP VIOLATION OF CEREBRAL CIRCULATION OF BLOOD • Sharp violation of cerebral circulation by the mechanism of development is related either to the hemorrhage in subdural space (haemorrhagic stroke) or with an ischemia of brain (ischemic stroke). Sometimes there is transition of ischemic stroke in haemorrhagic stroke.

22. References • 1. Scheinberg P. The biologic basis for the treatment of acute stroke. Neurology 1991; 41: 1867-73. • 2. Yamaguchi T, Minematsu K, Hasegawa Y. General care in acute stroke. Cerebrovascular Diseases 1997; 7: (suppl 3): 12-7. • 3. Adams HP Jr. Management of patients with acute ischaemic stroke.Drugs 1997; 54 (suppl 3): 60-70. • 4. Hacke W. Intensive care in acute stroke. Cerebrovascular Diseases 1997; 7 (suppl 3): 18-23. • 5. Wardlaw JM, Warlow CP, Counsell C. Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke.Lancet 1997; 350: 607-14. • 6. Practice advisory: thrombolytic therapy for acute ischaemic stroke _ summary statement: Report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology 1996; 47: 835-9. • 7. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke. Lancet 1997; 349: 1569-81. • 8. CAST (Chinese Acute Stroke Trial) Collaborative Group. Randomised, placebo-controlled trial of early asprin use in 20 000 patients with acute ischaemic stroke. Lancet 1997; 349: 1641-9. • 9. Zivin JA. Neuroprotective therapies in stroke. Drugs 1997; 54: (suppl 3) 83-9. • 10. Stroke Unit Trialists' Collaboration. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. British Medical Journal 1997; 314: 1151-9.