Dyscirculatory encephalopathy - Causes and pathogenesis

Causes of cerebrovascular insufficiency

The causes of both acute and chronic cerebrovascular accidents are the same. Atherosclerosis and arterial hypertension are considered among the main etiologic factors; a combination of these two conditions is often detected. Chronic cerebrovascular insufficiency can also be caused by other cardiovascular diseases, especially those accompanied by signs of chronic heart failure, heart rhythm disturbances (both constant and paroxysmal forms of arrhythmia), often leading to a drop in systemic hemodynamics. Anomalies of the vessels of the brain, neck, shoulder girdle, aorta, especially its arch, are also important; they may not manifest themselves until an atherosclerotic, hypertensive or other acquired process develops in these vessels. Recently, a major role in the development of cerebrovascular insufficiency has been attributed to venous pathology, not only intra-, but also extracranial. Compression of vessels, both arterial and venous, can play a certain role in the development of chronic cerebral ischemia. It is necessary to take into account not only the spondylogenic influence, but also compression by altered adjacent structures (muscles, fascia, tumors, aneurysms). Low blood pressure has an adverse effect on cerebral blood flow, especially in the elderly. This group of patients may develop damage to small arteries of the head associated with senile arteriosclerosis. Another cause of chronic cerebral circulatory failure in elderly patients is cerebral amyloidosis - deposition of amyloid in the vessels of the brain, leading to degenerative changes in the vessel wall with possible rupture.

Very often, cerebrovascular insufficiency is detected in patients with diabetes mellitus, they develop not only micro-, but also macroangiopathy of various localizations. Other pathological processes can also lead to chronic cerebrovascular insufficiency: rheumatism and other diseases from the group of collagenoses, specific and non-specific vasculitis, blood diseases, etc. However, in ICD-10, these conditions are quite rightly classified in the headings of the specified nosological forms, which determines the correct treatment tactics.

As a rule, clinically detectable encephalopathy is of mixed etiology. In the presence of the main factors of development of chronic cerebral circulatory failure, all other diversity of causes of this pathology can be interpreted as additional causes. Identification of additional factors that significantly aggravate the course of chronic cerebral ischemia is necessary for development of the correct concept of etiopathogenetic and symptomatic treatment.

Causes of cerebrovascular insufficiency

Main:

• atherosclerosis;
• arterial hypertension.

Additional:

• heart disease with signs of chronic circulatory failure;
• heart rhythm disturbances;
• vascular anomalies, hereditary angiopathies;
• venous pathology;
• vascular compression;
• arterial hypotension;
• cerebral amyloidosis;
• diabetes mellitus;
• vasculitis;
• blood diseases.

Pathogenesis of cerebrovascular insufficiency

The above diseases and pathological conditions lead to the development of chronic cerebral hypoperfusion, i.e. to a long-term under-receipt of the brain of the main metabolic substrates (oxygen and glucose) delivered by the blood flow. With slow progression of brain dysfunction developing in patients with chronic cerebral circulatory insufficiency, pathological processes unfold primarily at the level of small cerebral arteries (cerebral microangiopathy). Widespread damage to small arteries causes diffuse bilateral ischemic damage, mainly of the white matter, and multiple lacunar infarctions in the deep parts of the brain. This leads to disruption of normal brain function and the development of non-specific clinical manifestations - encephalopathy.

A high level of blood supply is necessary for adequate brain function. The brain, which accounts for 2.0-2.5% of body weight, consumes 20% of the blood circulating in the body. The average cerebral blood flow in the hemispheres is 50 ml per 100 g/min, but in the gray matter it is 3-4 times higher than in the white matter, and there is also relative physiological hyperperfusion in the anterior parts of the brain. With age, the cerebral blood flow decreases, and frontal hyperperfusion disappears, which plays a role in the development and increase of chronic cerebral circulatory insufficiency. Under resting conditions, oxygen consumption by the brain is 4 ml per L00 g/min, which corresponds to 20% of all oxygen entering the body. Glucose consumption is 30 μmol per 100 g/min.

In the vascular system of the brain, there are 3 structural and functional levels:

• the main arteries of the head - the carotid and vertebral, which carry blood to the brain and regulate the volume of cerebral blood flow;
• superficial and perforating arteries of the brain, which distribute blood to various regions of the brain;
• microcirculatory vessels that provide metabolic processes.

In atherosclerosis, changes initially develop mainly in the main arteries of the head and the arteries of the brain surface. In arterial hypertension, perforating intracerebral arteries that feed the deep parts of the brain are primarily affected. Over time, in both diseases, the process spreads to the distal parts of the arterial system and secondary reorganization of the vessels of the microcirculatory bed occurs. Clinical manifestations of chronic cerebral circulatory insufficiency, reflecting angioencephalopathy, develop when the process is localized mainly at the level of the microcirculatory bed and in small perforating arteries. In this regard, the measure for preventing the development of chronic cerebral circulatory insufficiency and its progression is adequate treatment of the underlying disease or diseases.

Cerebral blood flow depends on perfusion pressure (the difference between systemic arterial pressure and venous pressure at the level of the subarachnoid space) and the resistance of cerebral vessels. Normally, due to the mechanism of autoregulation, cerebral blood flow remains stable, despite fluctuations in arterial pressure from 60 to 160 mm Hg. In case of damage to cerebral vessels (lipogyalinosis with the development of vascular wall areactivity), cerebral blood flow becomes more dependent on systemic hemodynamics.

In long-term arterial hypertension, a shift in the upper limit of systolic pressure is observed, at which cerebral blood flow remains stable and autoregulation disorders do not occur for quite a long time. Adequate perfusion of the brain is maintained by increasing vascular resistance, which in turn leads to an increase in the load on the heart. It is assumed that an adequate level of cerebral blood flow is possible until significant changes in small intracerebral vessels occur with the formation of a lacunar state characteristic of arterial hypertension. Consequently, there is a certain reserve of time when timely treatment of arterial hypertension can prevent the formation of irreversible changes in the vessels and brain or reduce the degree of their severity. If chronic cerebral circulatory insufficiency is based only on arterial hypertension, then the use of the term "hypertensive encephalopathy" is justified. Severe hypertensive crises always involve a breakdown of autoregulation with the development of acute hypertensive encephalopathy, which each time worsens the symptoms of chronic cerebral circulatory insufficiency.

A certain sequence of atherosclerotic vascular lesions is known: first, the process is localized in the aorta, then in the coronary vessels of the heart, then in the vessels of the brain and later in the extremities. Atherosclerotic vascular lesions of the brain are, as a rule, multiple, localized in the extra- and intracranial sections of the carotid and vertebral arteries, as well as in the arteries that form the circle of Willis and its branches.

Numerous studies have shown that hemodynamically significant stenoses develop with a narrowing of the lumen of the main arteries of the head by 70-75%. But cerebral blood flow depends not only on the severity of stenosis, but also on the state of collateral circulation, the ability of cerebral vessels to change their diameter. The indicated hemodynamic reserves of the brain allow asymptomatic stenoses to exist without clinical manifestations. However, even with hemodynamically insignificant stenosis, chronic cerebral circulatory failure will almost certainly develop. The atherosclerotic process in the vessels of the brain is characterized not only by local changes in the form of plaques, but also by hemodynamic restructuring of the arteries in the area localized distal to the stenosis or occlusion.

The structure of plaques is also of great importance. So-called unstable plaques lead to the development of arterio-arterial embolism and acute cerebrovascular accidents, most often of the transient ischemic attack type. Hemorrhage into such a plaque is accompanied by a rapid increase in its volume with an increase in the degree of stenosis and aggravation of the signs of chronic cerebrovascular insufficiency.

When the main arteries of the head are affected, cerebral blood flow becomes very dependent on systemic hemodynamic processes. Such patients are especially sensitive to arterial hypotension, which can lead to a drop in perfusion pressure and an increase in ischemic disorders in the brain.

In recent years, two main pathogenetic variants of chronic cerebral circulatory insufficiency have been considered. They are based on morphological signs - the nature of the damage and the predominant localization. With diffuse bilateral damage to the white matter, a leukoencephalopathic, or subcortical Biswanger, variant of cerebrovascular insufficiency is distinguished. The second is a lacunar variant with the presence of multiple lacunar foci. However, in practice, mixed variants are often encountered. Against the background of diffuse damage to the white matter, multiple small infarctions and cysts are found, in the development of which, in addition to ischemia, repeated episodes of cerebral hypertensive crises can play an important role. With hypertensive angioencephalopathy, lacunae are located in the white matter of the frontal and parietal lobes, putamen, pons, thalamus, and caudate nucleus.

The lacunar variant is most often caused by direct occlusion of small vessels. In the pathogenesis of diffuse white matter damage, the leading role is played by repeated episodes of a drop in systemic hemodynamics - arterial hypotension. The cause of a drop in blood pressure can be inadequate antihypertensive therapy, a decrease in cardiac output, for example, in paroxysmal cardiac arrhythmias. Persistent cough, surgical interventions, orthostatic arterial hypotension due to vegetative-vascular insufficiency are also important. In this case, even a slight decrease in blood pressure can lead to ischemia in the end zones of adjacent blood supply. These zones are often clinically "silent" even during the development of infarctions, which leads to the formation of a multi-infarction condition.

In conditions of chronic hypoperfusion, the main pathogenetic link in chronic cerebral circulatory insufficiency, compensation mechanisms can be exhausted, the energy supply to the brain becomes insufficient, which first leads to functional disorders and then to irreversible morphological damage. Chronic cerebral hypoperfusion is characterized by a slowdown in cerebral blood flow, a decrease in the oxygen and glucose content in the blood (energy starvation), oxidative stress, a shift in glucose metabolism towards anaerobic glycolysis, lactic acidosis, hyperosmolarity, capillary stasis, a tendency to thrombosis, depolarization of cell membranes, activation of microglia, which begins to synthesize neurotoxins, which, along with other pathophysiological processes, leads to cell death. Granular atrophy of the cortical areas is often detected in patients with cerebral microangiopathy.

A multifocal pathological condition of the brain with predominant damage to the deep sections leads to disruption of connections between cortical and subcortical structures and the formation of so-called disconnection syndromes.

Reduced cerebral blood flow is necessarily combined with hypoxia and leads to the development of energy deficiency and oxidative stress - a universal pathological process, one of the main mechanisms of cell damage in cerebral ischemia. The development of oxidative stress is possible under conditions of both oxygen deficiency and excess. Ischemia has a damaging effect on the antioxidant system, leading to a pathological pathway of oxygen utilization - the formation of its active forms as a result of the development of cytotoxic (bioenergetic) hypoxia. The released free radicals mediate damage to cell membranes and mitochondrial dysfunction.

Acute and chronic forms of ischemic cerebrovascular accident may transform into one another. Ischemic stroke, as a rule, develops against an already altered background. Patients show morphofunctional, histochemical, immunological changes caused by the preceding cerebrovascular process (mainly atherosclerotic or hypertensive angioencephalopathy), the signs of which significantly increase in the post-stroke period. The acute ischemic process, in turn, triggers a cascade of reactions, some of which end in the acute period, and some persist for an indefinite period and contribute to the emergence of new pathological conditions, leading to an increase in the signs of chronic cerebrovascular insufficiency.

Pathophysiological processes in the post-stroke period are manifested by further damage to the blood-brain barrier, microcirculatory disorders, changes in immunoreactivity, depletion of the antioxidant defense system, progression of endothelial dysfunction, depletion of anticoagulant reserves of the vascular wall, secondary metabolic disorders, and disruption of compensatory mechanisms. Cystic and cystic-glial transformation of damaged areas of the brain occurs, separating them from morphologically undamaged tissues. However, at the ultrastructural level, cells with apoptosis-like reactions launched in the acute period of stroke may persist around necrotic cells. All this leads to aggravation of chronic cerebral ischemia that occurs before the stroke. Progression of cerebrovascular insufficiency becomes a risk factor for the development of recurrent stroke and vascular cognitive disorders up to dementia.

The post-stroke period is characterized by an increase in cardiovascular pathology and disturbances not only in cerebral but also in general hemodynamics.

In the residual period of ischemic stroke, depletion of the antiaggregatory potential of the vascular wall is observed, leading to thrombus formation, increasing severity of atherosclerosis and progression of insufficient blood supply to the brain. This process is of particular importance in elderly patients. In this age group, regardless of the previous stroke, activation of the blood coagulation system, functional insufficiency of anticoagulation mechanisms, deterioration of the rheological properties of the blood, disorders of systemic and local hemodynamics are noted. The aging process of the nervous, respiratory, cardiovascular systems leads to disruption of autoregulation of cerebral circulation, as well as to the development or increase of brain hypoxia, which in turn contributes to further damage to the autoregulation mechanisms.

However, improving cerebral blood flow, eliminating hypoxia, and optimizing metabolism can reduce the severity of dysfunction and help preserve brain tissue. In this regard, timely diagnosis of chronic cerebral circulatory failure and adequate treatment are very important.

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