What Is a Stroke?
Stroke is a type of cerebrovascular disease that involves the vessels of the central nervous system. It usually occurs with sudden onset due to a burst of cerebral arteries, hemorrhage or occlusion by a thrombus or other particles ischemia, leading to focal brain dysfunction. Immediately, nerve cells depleted of oxygen in the involved vascular territory will be functionally disturbed and die if the circulation is not promptly restored. Two main mechanisms may lead to ischemic stroke: occlusive or hemodynamic. These two situations decrease the cerebral perfusion pressure and eventually lead to cellular death. But within certain limits, the brain blood flow can be maintained by autoregulation of cerebral arteries and collateral circulation. When occlusion of an artery develops, blood flow in the periphery of the infarct core is usually reduced but still sufficient to avoid structural damage, so that the functional modifications of cells may be reversible if circulation is restored. This ring-like area of reduced blood flow around the ischemic center of infarct has been termed penumbra as an analogy of the half-shaded part around the center of a solar eclipse. It may largely explain the functional improvement occurring after stroke. Indeed, the neurons surviving in this critical area of infarct at reduced blood flow may again function as soon as blood flow and oxygen delivery is restored.
How Many Types of Stroke Are There?
Cerebral infarction is not a single disease and there are two main types of stroke: ischemic or hemorrhagic. Embolism is the most frequent cause of ischemic stroke. Embolism may originate from the heart, aortic arch or cervico-cephalic arteries. 70-80 of ischemic strokes are due to embolic migration. Intracerebral and subarachnoid hemorrhages are usually related to the rupture of an artery or arterioles. Their morbidity and mortality rates are higher than for ischemic stroke. Artery-to-artery embolism is the main cause of ischemic stroke. Rupture of atheromatous plaques is a potent cause of thrombosis. Indeed, the progression of atheromatous plaques leads to arterial stenosis, formation of wall thrombus, and finally occlusion with high probability of thrombi (e.g. embolism). The size and composition of emboli, and the collateral system may determine the size of infarcts. Usually, small platelet emboli are rapidly disaggregated and lead only to transient ischemic attacks by temporary occlusion of distal cerebral arteries. On the other hand, large thrombotic embolism, rich in fibrin, is therefore less friable and may cause more persisting and severe ischemia. The internal carotid artery at its origin (bifurcation) is the main site of atherosclerotic plaques, followed by the carotid siphon, the proximal and distal vertebral arteries and the mid-basilar artery. The onset of ischemic stroke is thus related to the onset of embolism, which is linked to vascular territories, dynamic changes in atherosclerotic plaques, and degree of stenosis. When atherosclerosis involves small cerebral arteries in the deep perforative network, especially in patients with hypertension or diabetes, small deep 'lacunar' infarcts may occur because, at this level, the arteries are terminal branches and have no collaterals. Microatheromatous or lipohyalinotic occlusion is the main cause of lacunar infarction. Intraparenchymal and subarachnoid hemorrhages are due to the rupture of the brain vessel wall. Spontaneous, intracerebral hemorrhage accounts for 10-15% of all strokes. The main mechanisms underlying hemorrhage include hypertensive arteriolopathy. arteriovcnous malformations, amyloid angiopathy, drugs (anticoagulants, thrombolytics) and inflammatory vasculitides.
How Frequent Are Strokes?
Stroke is the third main cause of death after heart disease and cancer, and the first cause of severe disability. One third of fatal strokes occur before age 65 years. For all stroke types combined, the mortality varies from country to country between 20 and 250 per 100,000 per year. In the USA strokes are the cause of 150,000 deaths per annum. Between 1969 and 1987, stroke mortality has significantly decreased in some developed countries: 40% for men and 45% for women in the USA. This fall is related with the introduction of effective treatment of risk factors (lowering hypertension, lifestyle management), and with the improvement of diagnostic accuracy and better management of the acute phase of stroke. Data obtained from 25 countries allow to conclude that a decrease in mortality of 3-5%} per annum had occurred in western European countries between 1970 and 1985. The incidence of stroke is estimated to be about 150 per 100,000 population per year in industrial countries. It has also decreased by about 20% during the 1980s. In the very first days, transtentorial herniation due to cerebral edema and brain compression represent the main cause of death. The first or second week after stroke onset, one of the causes of mortality after stroke is due to secondary complications of hospitalization immobility, e.g. chest infection (bronchopneumonia), venous thromboembolism.
Which Are the Warning Symptoms of Stroke?
Warning symptoms of stroke ('brain attack') include: Sudden weakness or numbness of the face, arm or leg on one side of the body. Sudden dimness or loss of vision, particularly in one eye, or Loss of speech, or trouble talking or understanding speech. Sudden, severe headaches with no known or apparent cause. Unexplained dizziness, unsteadiness or sudden falls, especially along with any of the previous symptoms. Sudden difficulty swallowing. If a patient feels any of these symptoms, even for a few seconds or minutes, he must consult a physician as soon as possible. When one of these warning signs is temporary and lasts less than 24 h. it corresponds to what has been called a transient ischemic attack or TIA. Up to 30% of strokes are preceded by TIA. A patient who has experienced one or more TIAs is 10 times more likely to develop a stroke than someone who has not. TIAs are an extremely important warning symptom and they must never be ignored.
Which Are the Effects of Stroke?
The heterogeneity of stroke pathogenesis and difference between stroke subtypes may hamper diagnosis and management. But usually, the neurological findings help to identify the location of lesions and to predict the stroke mechanism, which is fundamental for determining the initial investigations and treatment. Different patterns of weakness may be found in lesions of the middle cerebral artery (MCA) territory. Hemiplegia is related to large or deep MCA infarcts. Lesions in the upper branch of MCA produces hemiparesis with facio-brachial predominance. On the other hand. weakness predominates in the contralateral lower limb with lesions in the anterior cerebral artery territory. Sensory deficit is also common in MCA stroke, resulting from lesions affecting the territory of the posterior parietal artery. Usually, complete contralateral sensory loss is produced by lesions in the ventroposterolateral part of the thalamus. However, a pseudothalamic pattern may be found in infarcts involving the anterior parietal artery territory. Visual symptoms predominate in the posterior cerebral artery territory. Homonymous hemianopia or quadrantanopia may occur and pertubate walking or driving. They are sometimes associated with alexia or apraxia. Ocular disturbances, such as diplopia, are produced by lesions in the brainstem. They are often associated with hemiparesis or ataxia. Many patients can develop speech disorders, called aphasia, related to infarcts in the dominant hemisphere. It affects the capacity of speaking, listening, reading or writing. Neurobehavioral manifestations are also prominent in stroke and can involve the capacity of thinking and planning activities. Hemineglect is usually found in lesions of the nondominant hemisphere. After stroke, many patients develop a depression which can affect motor improvement. Deglutition or swallowing can also be affected by stroke, usually with medullary infarctions or bilateral lesions. Bronchoaspiration can occur in such cases.
Which Are the Risk Factors of Stroke?
There are two main groups of 'cardio-cerebrovascular' risk factors. The first group is genetically determined or related with natural body functions. On the contrary, the second is the result of lifestyle and can be modified. The risk factors may interact more than just by summation, so that the risk of stroke markedly increases as the number of risk factors increases. The unmodifiable risk factors are: age, sex, race, family history, and previous T1A or stroke. Age is the most powerful risk factor. Indeed, the risk of stroke doubles or triples with every decade after 50 years of age. Many studies have demonstrated a higher incidence of stroke in men than in women and the general decline in stroke in western countries also seems to have been particularly marked in women. According to risk factors and stroke etiology, the recurrence rate of stroke varies between less than 1% and more than 10% in the first year, with the first 6 months being the period of highest risk. Hypertension, diabetes, and smoking increase this risk. The main modifiable risk factors, which must be controlled to decrease the risk of stroke, include hypertension, smoking, high lipids, diabetes and alcohol intoxication. Hypertension is the most important risk factor for brain infarction. The relationships between blood pressure and the relative risk of stroke is nearly log linear. The effect of hypertension decreases in the very elderly, and the relative risk for stroke falls from 3.5 in people aged 50-59 years to 1.7 in those aged over 80. This risk factor is associated with large-artery atheroma, small-artery disease and intracerebral hematoma. Smoking, despite controversial data, is clearly a risk factor, dose-responsive. Diabetes is a major risk factor particularly when associated with hypertension. The metabolism of cholesterol is directly implicated in the development of atherosclerosis and plaques and high cholesterol is a stroke risk factor. The modifications of blood levels of lipids are related not only with eating habits but also with genetic factors.
How to Make the Diagnosis of Stroke?
An early and correct diagnosis of stroke is made by evaluating symptoms, reviewing the patient's medical history and risk factors, and performing routine tests. The clinical examination is crucial for the choice and timing of investigations. ECG and blood tests are usually the first laboratory investigations carried out in the emergency room. They must include sedimentation rate, red and white cell count, platelet count, hematocrit, blood ionogram, glucose, serum enzymes, cholesterol and lipids levels, and routine coagulation profile, including serum fibrinogen, prothrombin time and partial thromboplastin time. Brain CT scan is the most useful radiological investigation in the acute phase. Within about 20 min. it allows to distinguish between ischemic and hemorrhagic lesions and also to rule out nonstroke brain conditions. In the first hours after an ischemic stroke, a CT scan can be normal. But often indirect signs of stroke can be visualized: focal brain edema, obliteration of cortical sulcus, spontaneous hyperdense artery. The main limitations of CT are the detection of brainstem and cerebellar infarcts. Magnetic resonance imaging (MRI) is a technique which offers different possibilities to detect ischemic lesions in the acute phase of stroke. It is especially useful for brainstem infarcts. Compared with CT scan, MRI is more sensitive in the detection of recent and old strokes. MRI can improve stroke localization and detect small infarcts. It may also better allow to define the age of an ischemic lesion. MI has not replaced CT in the emergency phase of stroke, because of its availability and difficulty in differentiating recent hemorrhage from ischemia. With this technique, angiographic pictures (MR angiography or MRA) can also be obtained noninvasively. But a longer time and good collaboration of patients (no claustrophobia) are necessary to obtain good images. However, with reduction of examination time and costs, it is likely that more and more patients will have MRI in the acute phase, since it may give data on viable vs. irreversibly damaged tissue and underlying vascular lesions at the same time. Other investigations, such as Doppler ultrasounds, echocardiography, catheter angiography and other tests are usually made to determine the etiology of a diagnosed stroke, often in selected patients.
Which Tests Can Help in the Search of Stroke Etiology?
Doppler ultrasounds easily allow evaluation of the blood flow at the precerebral level in the carotid and vertebral artery systems. It can provide information on a potential arterial source of emboli and on arterial occlusion and is currently performed as a screening procedure before more invasive investigations. It can be made and repeated at the bedside and it can be completed by echotomography and transcranial Doppler. It is very useful to detect carotid stenosis or dissection. With good practice it can even avoid conventional angiography in many instances. Actually, conventional angiography is reserved for special situations with suspicion of multiple or intracranial stenosis, floating thrombus, arteritis, or uncommon angiopathies. Electroencephalogram is usually not performed in stroke patients, although it can sometimes be useful. It can provide information on stroke localization, whether deep or superficial, when CT is inconclusive. It may make it possible to differentiate stroke from migraine or epileptic seizure, although not always. In a comatose patient, it gives information on the depth of coma, functional asymmetry and may exclude associated epileptic seizures. In suspected cardioembolism, the investigations must include at least 24 h one- to three-lead electrocardiogram monitoring. Noninvasive studies also include echocardiography to look at the heart in selected patients. Indeed, cardioembolism is the cause of 25-30% of ischemic strokes. Transthoracic two-dimensional echocardiography gives reliable information on the ventricular wall and the aortic and mitral valves. It can exclude a left-ventricular thrombus and demonstrate intracardiac shunts when used with a contrast microbubble test. Transesophageal echocardiography represents an advantage for the assessment of the posterior part of the heart, particularly the left atrium and appendage. If provides information on atheromatosis and ulcerated plaques in the aortic arch. Its disadvantage is the endoscopic procedure, which necessitates a good cooperation of the patient. Cerebrospinal fluid examination is rarely required in acute stroke, but it can provide information on specific conditions, including cerebral venous thrombosis and vasculitis.
How to Treat a Patient with Acute Stroke?
Management of the acute phase of stroke is not the target of this brochure. In short, treatment must begin as soon as possible to ensure that no further damage to brain cells develops. Stroke is an emergency, like myocardial infarction. In the acute phase of stroke, it is critical that patients get adequate management for the prevention of early complications, such as elevated intracranial pressure and broncho-aspiration or infection, fever, deep venous thrombosis, pulmonary embolism, bed sores, and metabolic and hydroionic disorders. General and medical treatments aim at preserving the integrity of cells in the periphery of the infarct core (penumbra). As an example, patients should be maintained in a supine position to avoid a sudden decrease of brain perfusion pressure in the ischemic area, where autoregulation is lost. However, this position may be contradictory to the prevention of bronchoaspiration, so that management must be adopted to individual situations. Treatment of arterial hypertension is commonly considered when mean arterial pressure is above 160 mm Hg. Hyperthermia must also be avoided because the cerebral metabolic rate is proportional to body temperature and increases 5-17%/°C. Elevated glucose levels increase brain damage, and must be controlled. Encouraging findings have been demonstrated for hyperacute therapy of ischemic stroke with thrombolytic agents, mainly recombinant tissue plasminogen activator (rtPA). One multicentre study has shown significant and sustained neurological improvement when thrombolytic treatment is initiated within the first 3 h of stroke onset. Ongoing studies will allow to specify if therapy can be applied with a prolonged delay after onset of stroke. Neuroprotection with drugs acting on the ischemic cascade might be an extremely promising therapy in acute stroke, but it is still being evaluated with clinical trials. The early prevention of stroke recurrence, immediately after stroke, is a critical facet of stroke management. Recent data from the International Stroke Trial (1ST) and the Chinese Acute Stroke Trial (CAST) suggest that aspirin when administered as soon as possible in an acute stroke patient, mainly decreases the rate of early stroke recurrence. Even though low-dose heparin (or low-mo-lecular-weight heparin) is more controversial but is currently given in many centers in order to decrease the risk of venous thromboembolism and PE, high-dose heparin carries a higher risk of hemorrhage and should be avoided, except in selected indications (floating thrombus, minal thrombus. extracranial dissection, venous thrombosis) and with careful aPTT monitoring.
What to Do to Prevent Stroke?
The great majority of strokes are a consequence of atherosclerosis, with the development of atherosclerotic plaques in multiple arteries. Therefore, primary prevention, e.g. risk factors' management including anti-platelet agents, aims to slow down the formation of atherosclerosis. Regarding secondary prevention measures, a number of prospective studies have established that antiplatelet agents are effective in the secondary prevention of stroke, myocardial infarction and vascular death with a mean reduction of 25%. The ideal dosage of aspirin for stroke prevention is still debated. No study has been made to assess a potential difference between high-dose aspirin (950-1,300 mg a day) and very low dose, 30-50 mg a day. Meta-analysis of available data from clinical trials suggests that the best clinical effect is obtained with intermediate doses (200-325 mg a day). Other specific treatments for stroke prevention include other platelet aggregation inhibitors (possibly in combination with aspirin), anticoagulant therapy and specific surgical procedures (such as carotid endarterectomy). In addition, major risk factors must be considered, the most important one being hypertension: high blood pressure explains up to 25% of all strokes and a reduction of diastolic blood pressure of 6 mm Hg is associated with a reduction of 40%i of first strokes. Another one is atrial fibrillation for subjects over 65 years of age. Conventional oral anticoagulation is effective in patients with nonrheumatic atrial fibrillation. Lifestyle management is also essential (stop smoking, lose weight). The aim of this brochure is to address the main questions related to the issue of stroke prevention.
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