Stroke - Diagnosis

Diagnosis of stroke includes two phases. First, the fact of arterial occlusion must be established, which is usually confirmed by the characteristics of the course of the disease and the nature of the symptoms. Second, the cause of the occlusion must be identified. The second step is not of decisive importance for the choice of emergency therapeutic intervention, since treatment in most cases of ischemic stroke is carried out in the same way (regardless of its etiology) and includes measures to protect the brain and restore its blood supply. However, establishing the cause of the occlusion is important for choosing treatment aimed at preventing subsequent ischemic episodes.

It is useful to draw a comparison between cerebral and cardiac ischemia, despite the profound differences that exist between them. While advances in the treatment of myocardial ischemia have been rapid, advances in stroke therapy have been more modest and slower. By drawing parallels between cerebral and cardiac ischemia, it may be possible to identify new approaches to the treatment of cerebral ischemia based on the advances that have been made in myocardial ischemia.

Methods for diagnosing myocardial ischemia are well known to clinicians, and the clinical manifestations of this condition are well known to patients and their relatives. Thus, squeezing pain behind the breastbone, shortness of breath, profuse sweating and other signs of circulatory failure usually force patients to seek emergency medical care. In case of myocardial ischemia, patients immediately seek medical attention when a complex of symptoms appears, including intense pain and a feeling of imminent death. In those patients with cardiac ischemia who do not experience pain, the likelihood of timely diagnosis and treatment of the disease is significantly reduced, as is often the case among patients with diabetes.

At the same time, since stroke is not accompanied by pain, patients often do not attach importance to the initial symptoms. This leads to a delay in seeking medical care, and, accordingly, treatment is often postponed until the brain damage becomes irreversible. Thus, a patient who wakes up with a paralyzed arm may not know whether the weakness is caused by the fact that he "laid" the arm during sleep or whether he has had a stroke. Despite suspicions that it is something more than nerve compression, patients often delay seeking medical care in the hope of spontaneous improvement.

Diagnostic methods used for cardiac ischemia are significantly more reliable than those used for cerebral ischemia. Thus, the diagnosis of cardiac ischemia is clarified using electrocardiography (ECG), which is usually quite accessible, and its data are easy to interpret. ECG provides very important information, including information about previous episodes of ischemia, reversibility of current ischemia, localization of old and new ischemic zones.

In contrast, in cerebral stroke, diagnosis is based solely on clinical findings. The clinician must recognize the clinical syndrome caused by acute occlusion of a cerebral artery. Although occlusion of a large vessel, such as the middle cerebral artery, produces an easily recognizable syndrome, blockage of smaller vessels may produce symptoms that are difficult to interpret. Moreover, recognition of new lesions is difficult in the presence of prior ischemic injury.

There is no simple procedure to confirm a stroke diagnosis, such as an ECG. Although computed tomography (CT) and magnetic resonance imaging (MRI) can confirm a stroke diagnosis, they usually do not reveal changes at the time when symptoms have just appeared and treatment can be most effective. In this regard, a special responsibility in the diagnosis of stroke falls on the physician, who must link the resulting neurological syndrome with the loss of function in the basin of a particular vessel. In the acute phase of ischemic stroke, the main task of neuroimaging is to exclude other causes that can cause neurological symptoms, such as hemorrhage, tumors, or multiple sclerosis. In the case of acute development of a neurological defect, CT should be performed immediately, and MRI - after 1-2 days to confirm the diagnosis of stroke if neurological symptoms persist. Magnetic resonance angiography (MRA) is used in combination with other methods to establish the etiology of stroke.

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Diagnosis of the affected vessel

Ischemic stroke is manifested by the acute development of a focal neurological defect, characteristic of occlusion of one of the cerebral arteries. In most cases, the patient presents complaints reflecting the acute loss of function of one of the CNS departments, corresponding to the syndrome of damage to a certain artery. The condition for the correct diagnosis is knowledge of both the functional and vascular anatomy of the brain, since the clinical manifestations of the syndrome depend on the affected vessel. Emergency therapy, developed to date, should begin before neuroimaging methods can confirm the localization and size of the infarction. Thus, diagnostics should be rapid and based solely on clinical data.

Stroke is characterized by a rapid onset - slowly increasing symptoms are not typical of cerebral ischemia. Slow onset is possible only when there is a sequential occlusion of many small vessels. In this case, careful questioning will reveal a stepwise type of progression, typical of multiple successive small ischemic episodes. Multiple small infarctions lead to the development of vascular dementia, which can be distinguished from Alzheimer's disease by the presence of focal neurological symptoms and multiple discrete lesions on MRI and CT.

In ischemic stroke, the caliber of the affected vessel determines the size of the brain lesion and, accordingly, the prevalence of neurological symptoms: occlusion of a large vessel usually causes a more extensive neurological defect, while occlusion of small vessels causes more limited neurological disorders. The deep parts of the brain are supplied with blood by long penetrating vessels, which are predisposed to the development of occlusion with the formation of characteristic small-focal cerebral infarctions. Syndromes associated with occlusion of small vessels are often called lacunar, since in these cases, small pores (lacunae) are usually detected in the deep structures of the brain during autopsy. Vascular damage to the brain that leads to the appearance of corresponding symptoms is called, accordingly, lacunar stroke.

Although identification of the lesion is essential for the diagnosis of stroke, it is of limited value in establishing the etiology of stroke because the caliber of the lesion and the location of the occlusion do not allow one to determine its cause. To solve this problem, it is necessary to examine the entire vascular tree proximal to the occlusion to identify a possible source of embolism. Although small penetrating vessels may be damaged primarily, they are also often blocked by arterio-arterial emboli, which may originate in a larger vessel from which the artery branches, or by small emboli from the heart. In addition, the source of embolism may be the venous bed, if there is a right-to-left shunt in the heart.

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Neuroimaging methods and the progression of histological changes

There is no consensus on when to perform neuroimaging in a patient with suspected ischemic stroke, since at the time of symptom onset, it can only rule out tumor or hemorrhage. If symptoms are due to ischemia, MRI and CT will not detect changes in the brain until several hours later. Moreover, changes due to ischemia may not be detectable by these imaging techniques for several days. The situation is further complicated by the fact that in a significant number of stroke patients, CT and MRI do not detect focal changes at all.

Understanding the pathological changes that occur in stroke helps to understand why CT and MRI have limited clinical value in the acute phase of stroke. Depending on the level of hemoperfusion, the affected area of the brain may continue to experience energy deficit for many hours. When perfusion is completely stopped, for example, during cardiac arrest, energy deficit develops within minutes. With a minimal degree of ischemia capable of causing damage to brain tissue, energy deficit may appear after 6 or more hours. This is exactly how long it may take for changes to appear in the brain tissue that can be detected by histological examination. Even with energy deficiency, histological changes may be minimal, as indicated by the absence of ischemic changes at autopsy. Thus, if ischemic damage occurs instantly, then autopsy will reveal massive changes in the brain that occur at the time of death and are not associated with the primary ischemic lesion. Characteristic changes associated with ischemia occur only under the condition of perfusion of the affected area of the brain for several hours.

The degree of ischemia determines the speed and severity of pathological changes in the infarction zone. The most severe change is necrosis, characterized by a complete loss of tissue structure. Less severe damage is manifested by a selective loss of neurons with preservation of glia and tissue structure. In both cases, as pathological changes develop, excess water accumulates in the brain tissue, causing edema. Only later, as the necrotic area of the brain is reorganized, does tissue volume decrease.

CT and MRI are usually normal for the first 6 to 24 hours after symptom onset. Of the two neuroimaging techniques, MRI is more sensitive because it is better at detecting water accumulation, which appears hyperintense on T2-weighted images. Older infarcts appear hypointense on T1-weighted images.

Since it takes time for the changes characteristic of ischemic stroke to appear in the brain, MRI and CT cannot confirm the diagnosis in the first hours of the disease, but they can exclude other causes that can cause neurological symptoms. All patients with a pronounced neurological defect require urgent neuroimaging, primarily CT - to exclude other diseases, such as intracranial hemorrhage. It is advisable to postpone MRI for at least 1 day after the onset of symptoms.

Diagnosis of the cause of ischemic stroke

Ischemic stroke occurs due to occlusion of an artery and disruption of the blood supply to a certain area of the brain. Establishing the cause of the occlusion is necessary to select the most effective long-term therapy. To do this, it is necessary to examine the vascular bed proximal to the occlusion zone. For example, with occlusion of the carotid artery, the primary pathology can be localized in the heart, aorta, or the artery itself. The cause of occlusion of a small vessel extending from the carotid artery can be an embolus that forms at any level between the heart and this vessel.

Although it is tempting to assume that the pattern of onset and the location of the affected vessel may help to establish the etiology of the stroke, clinical experience shows that these features are unreliable. For example, although a stroke with an acute onset of symptoms that immediately peaks is often embolic in origin, a similar picture is possible in patients with carotid bifurcation lesions that may require surgical intervention.

The caliber of the vessel involved is also of little help in establishing the etiology of the stroke. On the one hand, small vessels may be occluded by an embolus originating in the heart or proximal to a large artery. On the other hand, the vessel lumen may be obstructed by an atherosclerotic plaque at the site of its origin from an intracranial artery or as a result of its primary injury. There is also some uncertainty regarding the concept of lacunar disease, which suggests that small penetrating arteries may have a special type of pathological changes. Although this process, called lipohyalinosis, certainly exists, it can explain the stroke only after more proximal cardiac and arterial pathology has been excluded.

The concepts of "stroke etiology" and "stroke risk factors" are also often mistakenly interchanged. Etiology is associated with pathomorphological changes directly responsible for the development of arterial occlusion. These processes may include the formation of a blood clot in the left atrium, atherosclerosis of the vessel wall, and hypercoagulability states. At the same time, risk factors are identified conditions that increase the likelihood of stroke. These factors are often multiple and can interact with each other. Thus, smoking is a risk factor for stroke, but not its direct cause. Since smoking causes various physiological and biochemical changes, there are a number of possible pathways that lead to an increased risk of stroke, including smoking-induced hypercoagulability or an increased risk of atherosclerosis.

Given the multiplicity of these effects, the influence of risk factors is complex. For example, arterial hypertension is a risk factor for atherosclerosis at several levels, including in small penetrating arteries, larger intracranial arteries, and the bifurcation region of the carotid arteries. It is also a risk factor for ischemic heart disease, which in turn can cause atrial fibrillation and myocardial infarction, which can lead to cardiogenic embolism.

It is therefore impossible to determine by examining a patient whether the stroke was caused by hypertension, diabetes, smoking, or some other single risk factor. Instead, the underlying condition that directly led to the arterial occlusion must be determined. This is of more than academic interest, since therapy aimed at preventing a subsequent stroke is selected taking into account the etiology.

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Methods of studying the cardiovascular system

A number of noninvasive techniques have been developed to identify cardiac or arterial lesions that are the cause of cerebral vessel occlusion. The general strategy is to rapidly identify any possible cause that requires immediate correction to prevent recurrent stroke. The choice of medication depends on the risk of stroke in a given pathology. As a rule, conditions with a high risk of stroke require the use of warfarin, while those with a low risk use aspirin.

In all patients with ischemia in the anterior vascular territory, noninvasive examination of the carotid arteries is indicated, mainly to establish indications for carotid endarterectomy. The effectiveness of surgical removal of atherosclerotic plaque during endarterectomy has been controversial for many years due to the lack of clear clinical evidence. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) demonstrated the effectiveness of surgical treatment. Since a significant advantage of the method was noted only in patients with stenosis exceeding 70%, the degree of stenosis should be primarily considered when determining indications for surgery, regardless of which carotid territory caused cerebral ischemia.

The standard noninvasive method for evaluating the carotid bifurcation is duplex ultrasound (ultrasonography), which provides reliable results when performed by a well-trained practitioner. An alternative is MRA, which has several advantages. While duplex ultrasonography provides information only about the carotid bifurcation, MRA can examine the entire internal carotid artery, including the siphon region. In addition, MRA can image the vertebral arteries and the entire circle of Willis. On the other hand, duplex ultrasonography, unlike MRA, does not require the patient to remain motionless for a long time in conditions that often provoke claustrophobia and, therefore, is more comfortable. Although the accuracy of MRA in identifying carotid bifurcation lesions is comparable to that of duplex ultrasonography, it has not been studied as thoroughly. Unlike MRA, duplex ultrasonography also provides information on blood flow velocity, which complements the anatomical data.

Because duplex ultrasonography can be performed more rapidly, it should be performed soon after admission in patients with anterior vascular bed lesions. If the results are negative, MRA can be performed later to identify pathology at other levels of the vascular system. Delayed MRA increases the likelihood of detecting the ischemic area with MRI.

Angiography remains the gold standard in cerebral vascular imaging. However, it carries a known risk of stroke and mortality of 0.5%. With the availability of noninvasive ultrasound and magnetic resonance imaging, angiography should be reserved for specific questions that may influence treatment decisions.

Transcranial Doppler (TCD) is a useful adjunct to detect intracranial vascular disease. Although TCD does not provide as much detail as duplex ultrasonography, the measurement of blood flow velocity and pulsatility provides important information about atherosclerotic lesions in the vessels of the circle of Willis. For example, if MRA shows changes in the basilar artery, the middle cerebral artery, TCD provides additional information that may be important for interpreting cerebral angiograms.

While ultrasound and MRA provide information about extracranial and intracranial vessels, echocardiography is the best method for identifying a cardiac source of embolism. Echocardiography is indicated in two distinct groups of patients. The first includes patients with cardiac pathology evident from history or clinical examination (eg, auscultatory evidence of valvular or other cardiac disease). The second group includes patients in whom the cause of stroke remains unclear. In approximately 50% of patients, stroke is preliminarily classified as “cryptogenic,” but many are subsequently found to have either an underlying cardiac pathology predisposing to embolism or a coagulation disorder. With intensive additional testing, the nature of the vascular lesion can be determined in most cases, especially when MRA is used for noninvasive evaluation of large intracranial vessels.

Several studies have shown that transthoracic echocardiography usually does not reveal the cause of stroke in cases where there is no history of cardiac pathology and no abnormalities are detected on physical examination of the cardiovascular system, which makes its use inappropriate in patients with cryptogenic strokes. This is also true for obese patients and patients with emphysema, for whom another technique, transesophageal echocardioscopy (TEC), is more informative. TEC is the method of choice in cases where pathology of cerebral vessels cannot be detected. During TEC, an ultrasound probe is inserted into the esophagus to better examine the heart, which in this case is not obscured by ribs and lungs. This way, the condition of the aorta can also be assessed, which allows identifying large or protruding atherosclerotic plaques on the aorta, which can serve as a source of embolism. In the absence of heart and vascular pathology, arterial occlusion may be a consequence of a hereditary or acquired blood clotting disorder. Some conditions, such as Trousseau syndrome, characterized by increased blood clotting due to a malignant neoplasm, may be the sole cause of stroke in patients with a healthy heart and unaffected cerebral vessels. Other conditions may only be a risk factor for stroke. These include, for example, the presence of antiphospholipid antibodies, which are often detected in the elderly and increase the risk of stroke. As in the case of cardioembolic stroke, in hypercoagulability with a high risk of stroke, long-term treatment with warfarin is indicated.