Stroke is an acute localized cerebral dysfunction caused by impaired cerebral blood circulation and is clinically manifested by signs and symptoms such as aphasia, limb paralysis, and sensory disturbances. Clinically, it usually includes cerebral infarction, transient ischemic attack (TIA), cerebral hemorrhage, and subarachnoid hemorrhage. In some literature, stroke refers specifically to cerebral infarction. In this article, stroke refers to acute cerebrovascular disease in a broad sense, while the main content will focus on information related to prevention and treatment of cerebral infarction.
Epidemiology of stroke in China
The incidence of stroke in China is the second highest in the world after Siberia, Russia. The annual incidence rate is about 250/100,000 people. There are about 3.5 million new cases each year, and the death rate is about 120/100,000. In the 1990s, the average annual incidence of stroke per 100,000 people in Beijing, Shanghai and Changsha was 135.0, 76.1 and 150.0, respectively, and the annual incidence of stroke was basically the same during the same period, with an increase in the incidence of ischemic stroke and a decrease in the incidence of hemorrhagic stroke. In addition, the age of stroke onset tends to be earlier.
Cerebral infarction
Cerebral infarction, also known as cerebral infarction, is irreversible damage to brain tissue caused by focal cerebral ischemia, which manifests clinically as focal neurological deficits such as hemiplegia, hemianopia, and aphasia. Clinically, cerebral infarction without obvious symptomatic manifestations and detected when CT or MRI scans of the brain are performed for other reasons (such as physical examination, etc.) is called asymptomatic cerebral infarction. The relevant concepts of cerebral infarction are as follows.
Cerebral thrombosis: cerebral infarction caused by in situ lesions of the cerebral artery wall (e.g. atherosclerosis, arteritis, etc.) resulting in occlusion or severe narrowing of the artery.
Cerebral embolism: cerebral infarction caused by emboli (blood clots, fat, etc.) entering and blocking cerebral arteries with blood flow.
Etiology and pathogenesis of cerebral infarction
Risk factors for cerebral infarction
Risk factors for cerebral infarction are a range of genetic traits, lifestyle and diseases whose presence increases an individual’s likelihood of developing cerebral infarction. Some of these factors are modifiable to varying degrees, and interventions to prevent cerebral infarction can be achieved by addressing these factors. Therefore, understanding these risk factors is of great importance for the clinical diagnosis of stroke, screening of individuals at risk for stroke, and the adoption of targeted preventive measures.
The risk of cerebral infarction in patients with transient ischemic attack (TIA) is particularly important, with 5% of patients experiencing an infarction within 2 days and 10% within 90 days after a TIA. The risk of cerebral infarction in the near future is further increased when the patient with TIA is >60 years old, has diabetes mellitus, and the attack manifests as hemiparesis, aphasia, and/or an attack lasting >10 minutes.
Pathology of cerebral infarction
Focal cerebral ischemia, i.e., a significant decrease in local cerebral blood flow, is primarily due to occlusion or severe stenosis of blood vessels caused by lesions of cerebral vessels (usually arteries), the most common cause of which is atherosclerosis, but can also be caused by inflammation (infectious or autoimmune) or injury of the arteries (e.g., endothelial dissection).
Blood component abnormalities such as true erythrocytosis, increased blood coagulation (antiphospholipid antibody syndrome, S protein, C protein or antithrombin III) can cause or promote occlusion of the vessel.
In severe cerebral artery stenosis, a sudden drop in blood pressure can cause a dramatic decrease in cerebral blood perfusion pressure and a decrease in distal blood flow in the area supplied by the stenotic artery, resulting in cerebral infarction. Causes of lower blood pressure include severe dehydration, acute blood loss, and improper use of antihypertensive drugs.
After cerebral ischemia occurs, a series of pathological biochemical changes are induced due to the rapid depletion of energy substances in the ischemic region. These alterations promote each other to accelerate cerebral ischemic injury, resulting in the so-called waterfall effect. These pathophysiochemical abnormalities include excessive oxidation of lipids, release of excitatory amino acids, generation of oxidative free radicals, intracellular calcium ion pooling, and other alterations, known as a long-standing hotspot in research on cerebral protection therapy.
After the onset of focal cerebral ischemia, irreversible institutional damage can occur within minutes in the core region of ischemia, called the core of infarction. In contrast, the surrounding brain tissue, which is less ischemic and has a later onset of damage, can be restored to a normal state if its blood supply is restored in time. Such an area is the so-called “semi-dark zone”.
After cerebral infarction occurs, acute cerebral edema occurs in the ischemic area. In the early stage of ischemia, the edema caused by the accumulation of intracellular water is intracellular edema, or neutrophilic edema, while a few hours later, the collapse of the blood-brain barrier caused by cerebral ischemia leads to the simultaneous leakage of intravascular components, including macromolecular substances, and water, resulting in vascular edema. Cerebral edema increases the contents of the cranial cavity, causing an increase in intracranial pressure. This results in increased blood pressure, increased pulse pressure difference, and slowed heart rate. When intracranial pressure is increased, it causes a decrease in cerebral blood perfusion pressure, which further aggravates cerebral ischemia. Severe cerebral edema can endanger the patient’s life by leading to brain herniation formation.
Classification and diagnosis of cerebral infarction
Classification of cerebral infarction (CVD-III)
Clinical disease type classification
C atherosclerotic thrombotic
C cardiogenic cerebral embolism
C lacunar cerebral infarction
C Other
Pathogenesis
C Thrombotic
C Embolic
C Hemodynamic
Diagnosis
Atherosclerotic thrombotic cerebral infarction
Cerebral artery thrombotic cerebral infarction occurs when atherosclerotic plaques in the intracranial and external arteries cause narrowing of the arterial lumen, and on top of this, when the atherosclerotic plaque is in an unstable state, wall thrombus forms on the surface of the plaque, further narrowing the lumen until it is completely occluded. If the wall thrombus on the surface of the artery that has not yet been mechanized is dislodged, it can form an embolus and enter the distal arterial branches with the blood flow, causing embolism, which is called artery-to-artery embolism and is an important mechanism of atherosclerotic thrombotic cerebral infarction. Another important type of atherosclerotic thrombotic cerebral infarction is hemodynamic cerebral infarction, also known as junctional zone cerebral infarction or watershed cerebral infarction.
When atheromatous plaque causes severe arterial stenosis, local cerebral blood perfusion is reduced to a critical state that barely maintains the metabolic needs of the brain, and this critical state is broken when cerebral arterial perfusion pressure is abruptly reduced, resulting in ischemia and infarction distal to the stenotic artery. The diagnosis of atherosclerotic thrombotic cerebral infarction is based on the following features.
Risk factors for atherosclerosis: hypertensive disease, diabetes mellitus, hyperlipidemia, etc.
Extracerebral atherosclerotic disease: coronary artery disease, limb artery occlusive disease, narrow carotid atherosclerosis, etc.
Antecedent TIA manifestations
Static or dynamic onset, progressing to peak in a few hours to a few days
No or only mild headache or disturbance of consciousness
Syndromes of cerebral artery trunk occlusion: hemiparesis, aphasia, etc.
Imaging manifestations of cerebral artery occlusion
Diagnosis of TIA
It is generally believed that the cause of TIA is atherosclerosis. The main basis for the diagnosis of TIA is as follows.
Atherosclerotic risk factors and related diseases
Transient: episodes lasting from a few minutes to more than 10 minutes and not more than 24 hours (usually <1 hour)
Stereotypic focal neurological deficits
Internal carotid artery system: hemiparesis, aphasia, transient blackness
Vertebrobasilar system: vertigo, diplopia, tetraplegia
No evidence of acute cerebral infarction on brain MRI scan
Diagnosis of watershed cerebral infarction
Risk factors for atherosclerosis: hypertensive disease, diabetes mellitus, hyperlipidemia, etc.
Extracerebral atherosclerosis: coronary artery disease, limb artery occlusive disease, carotid artery atherosclerosis, etc.
Sudden drop in cerebral perfusion pressure: rapid hypotensive treatment, acute blood and salt loss, cardiogenic shock, etc.
Neurological deficits
Imaging manifestations of cerebral infarction with cross-sectional distribution
Cardiogenic cerebral embolism
When a cardiac disorder provides a source of emboli such as blood clots in the heart, they can be dislodged and cause cardiogenic cerebral embolism. The diagnosis of cardiogenic cerebral embolism requires the presence of a cardiac disorder that provides the source of the embolus and the sudden onset of cerebral embolism. The diagnosis of cardiogenic cerebral embolism is based on
Cardiac disorders providing the embolus: atrial fibrillation, acute myocardial infarction, bacterial endocarditis, cardiac mucinous tumor, etc.
Sudden onset of neurological deficits with transient (within seconds) peaks
Neurological deficits: hemiparesis, aphasia, etc., with epileptic seizures
No or only mild headache, impaired consciousness
Imaging manifestations of cerebral artery occlusion
Lacunar cerebral infarction
Pathologically, lacunar cerebral infarction is called lacunar cerebral infarction when the maximum diameter of the lacunar space does not exceed 1.5 cm after cerebral infarction. Luminal cerebral infarction is more likely to occur in patients with hypertension and diabetes mellitus. It is generally believed that luminal occlusion due to lipid vitreous degeneration in the basal ganglia or small penetrating arteries of the cerebral bridge caused by hypertension is the main cause of lacunar cerebral infarction; however, when atherosclerotic lesions at the exit of the penetrating branches of major cerebral arteries can also block the exit of the penetrating arteries, thus causing lacunar cerebral infarction. The diagnosis of lacunar cerebral infarction is based on the following points.
History of hypertension and/or diabetes mellitus
Acute onset, with neurological deficits peaking within hours
manifestations of various lacunar syndromes: common lacunar syndromes include simple motor mild hemiparesis, simple sensory stroke, dysarthria hand clumsiness syndrome, ataxia mild hemiparesis, etc.
Imaging: deep small punctate lesions
Ancillary tests for cerebral infarction
Laboratory tests for cerebral infarction
Laboratory tests for acute cerebral infarction include routine blood, blood glucose, blood lipids, renal function, blood electrolytes, blood gas analysis, cardiac enzymology, coagulation series, C-reactive protein, etc. Sometimes, indicators such as syphilis serology, anti-cardiolipin antibody, autoantibodies, etc. are also required.
Imaging diagnosis of cerebral infarction
Head CT, brain MRI, brain MRA, carotid ultrasound, transcranial Doppler cerebrovascular ultrasound (TCD), brain digital subtraction angiography (DSA), etc.
Treatment of cerebral infarction
Treatment of acute phase
The treatment principles of acute cerebral infarction include the reconstruction of cerebral blood flow as soon as possible, cerebral protection treatment, treatment of cerebral edema and high cranial pressure crisis, management of comorbidities, and early rehabilitation treatment.
Pre-hospital management: In the pre-hospital stage, the diagnosis and classification of stroke are not yet clear, so transport to the nearest hospital with examination and treatment conditions is the first priority of pre-hospital management. During transport, the patient should generally be placed in a flat position, and attention should be paid to protecting the airway and preventing the inhalation of vomitus and other airways. In patients without manifestations of hypoxia, oxygen inhalation has no practical significance. When the blood pressure is below 170 mmHg, the use of antihypertensive drugs, especially sublingual nifedipine, is generally unnecessary. However, if the patient shows signs of agitation or onset during exercise, headache, vomiting, neck resistance, etc., and cerebral hemorrhage is more likely, appropriate antihypertensive measures can be taken.
General management: The limbs should be kept in a functional position. In the acute stage with vomiting, dysphagia or unconsciousness, the intake of water should be controlled to prevent vomiting and accidental aspiration. Pay attention to the protection of the respiratory tract and inhale oxygen if necessary.
Thrombolytic therapy.
rtPA (recombinant tissue fibrinogen activator) can be used, 0.9 mg/kgBW, 10% of the full dose iv within 1 minute and the remaining dose intravenously within 1 hour.
t-PA restores blood supply to the semidark zone and is the only FDA-approved drug for cerebral infarction. results of the NINDS tPA Stroke Study showed a 30-50% increase in the treatment group without residual mild disability (treated within 3 h) and a 9% mortality rate (20% in the control group) if thrombolysis was performed within 3 h of onset. However, symptomatic cerebral hemorrhage did increase to 6.4%, higher than the 0.6% in the control group. tPA is indicated for the following indications.
l ischemic stroke, onset ≤ 3 hours
l no history of trauma or major surgery within the last 2 weeks, no gastrointestinal or urinary tract bleeding within 3 weeks, no history of severe cranial trauma, surgery, or stroke within 3 months, and no previous history of intracranial hemorrhage
l No rapid and significant improvement of symptoms after onset.
l No convulsions at onset (Todd palsy excluded)
lBp in the absence of major operations: < 185/110 mmHg
lBrain CT: no intracranial hemorrhage, early signs of cerebral ischemia not extending beyond 1/2 of the middle cerebral artery region
l. Blood glucose: 50-400 mg/dL, excluding hypoglycemia and hyperglycemia
PT < 15: If no anticoagulant drugs are being used, the drug can be administered after blood collection, and stop the drug immediately if the result is too high
l. Platelets > 100,000/mm3
Or use urokinase, 1-1.5 million units, 10% iv of the full dose, and the remaining dose should be given intravenously within 1 hour. Indications and contraindications as above.
Anticoagulation therapy
C low molecular heparin: effective in infarcts due to large arterial lesions (MRS)? Reduction of deep vein thrombosis and pulmonary embolism?
C Warfarin: progressive stroke with concomitant monitoring of PT (INR)
Antiplatelet therapy
C Aspirin: routine use
C Clopidogrel: second-line drug
Hemodilution: use low molecular dextrose or 706 plasma substitute, for those considering a cause of low perfusion
Cerebral protection therapy
Subcritical therapy
Edaravone: free radical scavenger, protective if used within 24 hours of onset, usually 30 mg, IV, b.i.d, 14 days/course.
Blood pressure management: systolic blood pressure within 220 and diastolic blood pressure below 120 mmHg during the acute period, allowing free fluctuations in term. Timely adjunctive voiding and reduction of various discomfort symptoms in patients contribute to blood pressure stabilization, but for patients treated with thrombolysis, blood pressure should be maintained below 170/100 mm Hg to reduce hemorrhagic transformation of the infarct.
Treatment of cerebral edema and high cranial pressure
Mannitol: note its renal damage, 250 ml, use intervals depending on the degree of increased intracranial pressure.
Mannofructose: less renal damage, can provide partial calories, but with intravascular hemolysis, elevated blood glucose, and non-ketotic hyperosmolar coma
Tachyphylaxis: indicated in the presence or concern of left heart insufficiency, and when renal impairment is present, the dosage of mannitol can be appropriately reduced.
Human albumin: the effect of general dose use on cerebral infarction and cerebral edema has not been clarified.
Hypothermia therapy: It can significantly reduce cerebral edema in animal tests, and clinical use is still being explored.
Craniotomy decompression: for large cerebral infarcts (so-called “malignant cerebral infarcts”), and for small cerebral infarcts, mortality can be reduced.
Ventricular puncture and drainage: can be used when obstructive hydrocephalus occurs, resulting in a rapid increase in intracranial pressure.
Management of Comorbidities
Infection
Pulmonary infections: diabetes mellitus, bed rest, swallowing disorder
Urinary tract infection: bed rest, catheter
Stressful upper gastrointestinal bleeding: can be prevented with antacids
Decubitus ulcers
Lower extremity deep vein thrombosis, pulmonary embolism
Prevention of cerebral infarction
1, systemic atherosclerotic lesions: including coronary heart disease, cardiac insufficiency, symptomatic peripheral arterial lesions, etc. Treatments for these diseases, such as anti-platelet drugs, can reduce the incidence of stroke at the same time.
2, hypertension: lowering blood pressure (especially systolic blood pressure) can reduce the incidence of cerebral infarction and cerebral hemorrhage. Generally, blood pressure should be controlled below 140/90 (below 130/80 in diabetic patients). Be aware of the risk of hypoperfusion cerebral infarction from antihypertensive therapy, and a phased and gradual lowering regimen is more prudent in patients with chronic hypertension, chronic diabetes, and cerebral artery stenosis.
It is not clear whether a particular antihypertensive drug has a better preventive effect on cerebral infarction. In a controlled study of 9,193 cases, colesartan reduced the incidence of stroke by 25% compared with atenolol for the same antihypertensive effect. The Systolic Hypertension in Europe (Syst-Eur) Trial (n = 4695) demonstrated that calcium antagonists for systolic hypertension reduced the incidence of stroke by 42%. In the Systolic Hypertension in the Elderly Program (SHEP) trial, the use of thiazide diuretics alone or with beta-blockers reduced the incidence of stroke by 36%.
3. Diabetes: In patients with diabetes, blood pressure should be strictly controlled below 130/80, and statins should be added to lower blood lipids. A study by the Prospective Diabetes Study Group found that strict blood pressure control (mean blood pressure of 144/82 mm Hg) was associated with a 44% reduction in the relative risk of stroke (RR) compared with casual blood pressure control (mean blood pressure of 154/87 mm Hg). In the Systolic Hypertension in the Elderly Program, antihypertensive therapy reduced the risk of stroke by 20% in patients with diabetes. In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, in a subgroup of diabetic patients with hypertension and ECG suggestive of left ventricular hypertrophy (n = 1195), ARB and β-receptor therapy were associated with an equivalent antihypertensive effect. In a subgroup of diabetics with hypertension and ECG suggestive of left ventricular hypertrophy (n = 1195), ARB was associated with a 24% reduction in major vascular events and a 21% reduction in strokes compared with beta-blockers for the same blood pressure reduction.
The UK Heart Protection Study (HPS) found that adding a statin lipid-lowering drug to the treatment of high-risk patients reduced the incidence of stroke in diabetics by 24%. In the Collaborative Atorvastatin Diabetes Study (CARDS), type II diabetic patients with more than one other risk factor received atorvastatin therapy, which reduced the incidence of stroke by 48%.
4. Atrial fibrillation: In principle, patients with atrial fibrillation should be treated with anticoagulation. However, the risk of stroke in patients with atrial fibrillation varies considerably. The CHADS2 (see table below) is a classification for heart failure, hypertension, advanced age (age ≥75), diabetes mellitus, and stroke or TIA. ADS2 is an abbreviation for prior stroke or TIA. Each of these is scored as one point, except for prior stroke or TIA, which is scored as two points. In practice, individuals with a prior stroke or TIA are considered to be at high risk and are treated with warfarin anticoagulation. In addition to the risk of stroke, the patient’s personal wishes, the risk of bleeding, and the condition of coagulation (INR) monitoring are important in the decision. The table below lists the target INR (International Normalized Rate of prothrombin time) values to be achieved with anticoagulation therapy, which can be used as a reference in practice. In anticoagulation therapy, attention should be paid to blood pressure control.
5. Lifestyle: (1) Diet should generally include more vegetables and fruits and reduce sodium intake (<=2.3g/day). Eating low-fat dairy products and reducing the intake of animal fat may help in stroke prevention. (2) Physical recreation may reduce the risk of stroke. 30 minutes or more of moderate-intensity exercise per day is an essential component of a healthy lifestyle. (3) Reducing body weight can lower blood pressure, which may contribute to stroke prevention.
(6) The relationship between alcohol consumption and stroke incidence is a so-called “J” curve, i.e., a small amount of moderate alcohol consumption can reduce the incidence of stroke, while a large amount of alcohol consumption can increase the incidence of stroke. Moderate alcohol intake can be determined as follows: no more than 24 grams of alcohol per day for men and no more than 12 grams for non-pregnant women.
7, oral contraceptives (OCs): early reports of the relationship between OCs and stroke are mainly related to the first generation of OCs, 2 generations later OCs contain lower amounts of estrogen and the risk quotient of causing stroke is not certain, in view of the few relevant reports suggesting possible risks, it is recommended that women with hypertensive disease, diabetes, smoking, a history of migraine and thromboembolic disease avoid using oral contraceptives.
8. Sleep apnea: can increase the risk of hypertensive disease. May directly increase the risk of stroke. For patients with drug-resistant hypertension, especially those with increased abdominal fat, screening and treatment of sleep apnea is recommended.
9. Hyperhomocysteinemia: Fasting Hcy over 16 μmol/L. There is a positive correlation between plasma Hcy levels and the risk of stroke. Taking folic acid and B vitamins may help in stroke prevention.