MINISTRY OF HEALTH OF THE REPUBLIC OF UZBEKISTAN
Tashkent Medical Academy
ACUTE ISCHEMIC
STROKE: MODERN APPROACHES
DIAGNOSIS AND TREATMENT OF INTEGRATED
(Guidelines)
Tashkent,2013
Establishment of the developer
Department of Nervous Diseases TMA
Compiled by:
Saidvaliev FS - Ph.D., assistant professor of nervous diseases TMA
Muratov, FH - Ph.D., assistant professor of nervous diseases TMA
Daminova H.M., Shamsieva U.A. ., assistant of nervous diseases TMA
Umarov, RR, - Members of the department of nervous diseases TMA
Reviewers:
Rizamuhamedova MZ - Head of the Department of Faculty Therapy TMA
Mirdzhuraev EM. - Professor of Nervous Diseases TMA
In the methodological recommendations given current understanding of acute cerebral circulatory disorders, the possible
mechanisms of their development shows variations of the clinical course of various types of strokes, their diagnosis and
differential diagnosis.Modern approaches the treatment of stroke, in particular, is presented in detail decongestant therapy.
Guidelines are intended for physicians, neurologists, general practitioners, internists, senior students and teachers of medical
colleges and universities.
Background,
epidemiology,
basic
etiological
factors
of
stroke
According to international epidemiological studies, strokes are the leading place in the structure, both mortality and disability
of the population and are a serious health and socio-economic problem for society [11, 14, 17, 23, 26, 48, 78, 93, 111,
119 ].Statistical studies in several countries of the CIS, including Uzbekistan, evidence of rejuvenation strokes and increase
the proportion of young women and an increase in new cases of stroke in rural residents [14, 15, 16].
The incidence of stroke in Russia is 2.5 - 3 cases per 1000 population per year, the mortality rate - one case per 1000
population per year. Mortality in acute stroke in Russia reaches 35%, increasing by 12-15% by the end of the first year after
stroke.Post-stroke disability ranks first among all causes of disability and is 3.2 per 10,000 population. Returns to work 20%
of stroke, despite the fact that one third of becoming ill with a stroke - people of working age. Approximately half of cases of
stroke
die
within
the
first
year
and
80%
of
survivors
are
disabled.
Despite the fact that crucial in reducing mortality and disability due to stroke belongs to primary prevention, a significant
effect in this regard, optimization of the system provides care to patients with stroke, the introduction of therapeutic and
diagnostic standards for these patients, including rehabilitation measures and the prevention of recurrent stroke.
The European regional office of the World Health Organization (WHO) believes that the creation of a modern system of care
for patients with stroke will reduce the mortality rate during the first month of the disease to the level of 20% and to ensure
independence in daily living 3 months after the onset of the disease at least 70% of survivors.
Development and implementation of common principles of management of patients with acute ischemic should help to
optimize the diagnostic approach and the choice of therapeutic measures to ensure the best outcome.
In the analysis of stroke to date, its most common causes are hypertension, atherosclerosis and vasculitis of vessels. From a
clinical point of view, these three processes often occur simultaneously. Defining the role of each of these factors in the
occurrence of stroke is of great theoretical and practical importance. Despite the diversity of etiological pathology of the
main extra-and intracranial vessels in rheumatism, hypertension and atherosclerosis, they often lead to the development of
severe complications such as acute ischemic stroke [1, 2, 3, 6, 15, 17, 18, 42, 42, 49, 62, 65, 97, 116, 159]. The complexity
and multi-factor of ischemic stroke necessitates a comprehensive study of some aspects of their pathogenesis. At present, it is
clear that pathological organic lesions of the vascular wall accompanied by hemodynamic disturbances in the main
extracranial vessels of the brain [27, 40, 42, 49, 54, 63, 65, 82, 91, 94, 110, 128, 142, 144, 146, 176, 187, 193, 194, 197].
The structure of cerebrovascular disease is currently dominated by ischemic brain damage. The problem of ischemic stroke is
not new, however, high levels of mortality and disability, as well as a tendency to increase the incidence maintain its
relevance over the decades [12, 16, 18, 26, 36, 48, 67, 90, 99, 116, 120, 121, 130, 183].Incidence, mortality and disability
associated with stroke, is one of the first places in the world [14, 17, 23, 24, 26, 46, 63, 67, 88, 90, 93, 99, 100, 116, 119, 120,
121,
127,
130,
205].
Stroke - the most common cause of disability in the West, the source of the enormous costs in the health system ranks third
in the list of causes of death [196, 198]. In Europe, each year one million AI [152]. Every year in the U.S., about 3 million
people are diagnosed with stroke, 450,000 suffer from the newly established stroke and about 150,000 die of stroke
[185]. High mortality rates observed in Northern Europe [46, 206] and the lowest in North America [175]. For women, first
place in the mortality rate is the South-West Pacific, and the lowest mortality rates in North America and Central Europe
[170].
Conducted at the international congresses of the European initiative group for stroke and the NINDS (National Institute of
Neurologic Disease and Stroke trial) looked at various aspects of the pathogenesis, diagnosis, treatment and prevention of
stroke [17, 23, 26, 76, 204, 206]. In recent years there has been a trend toward increased incidence of vascular diseases of the
brain. Many of the conditions of modern life (urbanization, acceleration and complexity of work processes, the rhythm of life
in general, hypokinesia, significant psycho-emotional stress) led to "rejuvenation" of stroke. The progressive increase in the
number of cerebral stroke and "rejuvenation" is a consequence of increasing the proportion of hypertension, atherosclerosis
and rheumatic lesions of the brain vessels, which play a key pathogenetic role in the development of acute disorders of
cerebral
circulation.
The most significant independent risk factor for ischemic stroke has rightly recognized as hypertension [19, 60, 62, 63, 64,
80, 86, 89, 91, 105, 123, 127, 157, 166, 189]. Most researchers have noted an increase in relative risk of stroke by about a
factor of 4 when the systolic blood pressure of 160 mm. mercury. of Art. and diastolic 95 mm. mercury. of
Art. [62]. Installed directly proportional relationship between the level of blood pressure and risk of stroke. This dependence
is observed not only among patients with arterial hypertension (hypertension), but also among people with normal blood
pressure (normotensive). The lower blood pressure, the lower the risk of stroke. Increased blood pressure is often seen in the
early days of ischemic stroke is not only in patients with hypertension, but also normotensive. The reasons for the transient
increase in blood pressure during the first days of stroke are assumed as follows: violation of autoregulation of cerebral blood
circulation, stress reaction to hospital admission, increased intracranial pressure, increased levels of norepinephrine in the
blood serum.The rise in blood pressure may be an adaptive response aimed at increasing cerebral blood flow in the area of
cerebral ischemia. Increased blood pressure at admission is regarded as a favorable prognostic sign of ischemic stroke,
although the persistence of high blood pressure for 1 day is not associated with a favorable outcome of stroke.Most
researchers do not recommend the use of antihypertensive drugs for 7-10 days after ischemic stroke, but if, before the
occurrence of stroke patients regularly took antihypertensive drugs, they are included in the therapy and after its
development.Preservation of high blood pressure based on the fact that his decline in the early days of a stroke can lead to a
reduction of cerebral blood flow and an increase in heart attacks. The exception is a significant increase in blood pressure
when the systolic blood pressure rises to 220 mm Hg. of Art. and higher, and diastolic blood pressure - up to 120 mm Hg. of
Art. and above. To date, no randomized clinical trials have proven the effectiveness of antihypertensive therapy in acute
ischemic stroke [63]. The systematic treatment of hypertension was observed reduction of all types of stroke by 38% of fatal
cases of stroke by 40% [195] and reduced stroke by 40% was observed even among patients older than 80 years [203].
There are several major factors influence the risk of hypertension in acute cerebrovascular disorders: the formation of
hypertensive microangiopathy, exacerbation of atherothrombotic arterial disease of large and small calibres, the
destabilization of atherosclerotic plaques and the occurrence of emboli, anevrizmatizatsiya (thinning) of the vascular
wall. Often these disorders develop in parallel [63, 64, 69, 80, 89, 127, 166, 188]. Violations of the walls of the great vessels
of the head in hypertension include the development of endothelial dysfunction, thickening of the intima - media, especially
the carotid arteries, and as a consequence of the progression of atherosclerosis and the formation of atherothrombosis [62,
166,
194,
187].
In the arterial vessels of the brain. AG runs the processes of hypertrophy and remodeling, leading to a decrease in their
internal diameter [127]. There is a range of destructive, adaptive and reparative reactions involving vessels of any size - as
large extra-and intracranial and smaller (up to 500 microns in diameter) of arteries and vessels of the microvasculature
[123]. It is important that hypertension contributes to the progression of atherosclerotic processes in large arteries, the
formation of pathological deformation and twisting, as well as the progression of various diseases of the heart, which in turn
contributes
to
the
deepening
of
cerebral
ischemia
[27,
30,
80,
87,
108].
Atherosclerotic vascular lesions of the brain is the most common cause of ischemic stroke [1, 5, 6, 25, 33, 49, 54, 55, 57, 65,
74, 82, 115, 128, 130, 142, 144, 179 , 194, 198]. Atherosclerosis is a multifocal disease [65]. Lesions of precerebral arteries
in patients with ischemic brain disease is common. The most dangerous localization of atherosclerotic plaques is their
location in the heart and blood vessels of the brain [25], especially in the carotid arteries. In 87% of affected two or more
arteries. In two thirds of observations suffer from three or more vessels of vascular pools in the brain. In 70% of patients
show complete occlusion of at least one of precerebral arteries, and 90% of hemodynamically significant
stenosis. Atherosclerotic changes are mainly in the initial segments of the extracranial parts of the arteries supplying the
brain. Intracranial lesions detected in at least four times. Occlusion and stenosis most often affect the carotid arteries (54-57%
of cases) and the carotid, in general (20% more than basilar). In the common carotid multilevel (echeloned or tandem), the
defeat of one of the vascular pool.The characteristic location of atheromatous process - the most common cause of carotid
artery blockage - is the initial part of the internal carotid artery. Much less frequently (4-5 times) thrombosing artery in the
cranial cavity of the siphon [42, 50, 73, 144]. Often atherosclerotic stenosis, and sometimes complete blockage occur in the
initial part of the common carotid or innominate artery in aortic arch. Blockage of arteries in the pyramid of the temporal
bone or at other sites is very rare [193]. Blockage of the internal carotid artery bifurcation is often combined with stenosis or
complete obliteration of the external carotid artery. In these cases, atherosclerotic plaque and thrombus, and captures the
distal part of the common carotid artery immediately below the bifurcation. Because of unknown reasons even
atherosclerotic lesions of the internal carotid artery in the neck predominate in males (3 - 3 ½ times more likely than women)
[33, 39, 72, 74, 94, 140, 142, 149, 160, 167, 176, 179, 181, 186, 187, 192, 194, 199].Clinical manifestations of
atherosclerotic occlusive process in the carotid artery usually recorded between 50 and 70 years, but often occur in a younger
age, which is not typical for vascular lesions of the brain. This will explain the earlier appearance of atherosclerotic changes
in the initial part of the internal carotid artery compared with the intracranial vessels. In patients with cerebral infarction
younger than 45 years in most cases, it was discovered lesion (atherosclerotic) extracranial carotid or of the vertebral
arteries. Changes in the brain, their prevalence and severity depended on the place of carotid artery occlusion. What
thrombosing distal carotid artery, ie, the more limited possibilities of collateral circulation, the greater the suffering
brain. When the carotid artery occlusion in the neck there are cases when the brain of patients (who died of any other reason)
does not show any change up to 15% of all cases of carotid artery occlusion in the neck remain latent, due to the development
of
high-grade
collateral
circulation
[126,
199 ,
209].
A considerable place among the risk factors for ischemic stroke is cardiac pathology, in which the frequency of atrial
fibrillation in the lead. It is one of the most important precursor of ischemic stroke, the more that the probability of
occurrence and distribution of its increase with age - every 10 years after 55 years abroad incidence of atrial fibrillation is
doubled [9, 38, 44, 45, 106]. According to a study in 1996, the prevalence of atrial fibrillation among the U.S. population is
growing and in persons over 65 years is 5%. It is believed that the aging U.S. population and rising incidence of atrial
fibrillation increases the incidence of and mortality from stroke [175]. It is known that more than half of cardioembolic stroke
occurs on the background of existing atrial fibrillation [38, 106, 118, 119, 129, 137, 156].
Independent risk factor for the development of AI is considered diabetes. According to a study Framingham, patients with
impaired glucose tolerance have double the risk of AI, regardless of its relationship with hypertension [138, 172, 191]. It is
known that persons suffering from diabetes, have a thick wall of the carotid arteries as a result of early atherosclerosis [139,
151, 190]. According to others, diabetes mellitus, when the AI plays a significant role in the defeat of the small vessels of the
brain, and therefore in the event of multiple lacunar infarcts of the brain, including ischemic lesions deep localization of
[193].
. A number of studies in assessing the significance of raising the level of fibrinogen revealed the close relationship between
coronary artery disease and atherosclerosis of major arteries, which makes high levels of fibrinogen in the blood marker of
cardiovascular disease and risk factor for ischemic stroke [73, 82, 95, 142, 156, 157, 160, 168, 169, 191].
It should be noted that the level of C-reactive protein is a sensitive indicator, indicating the presence of systemic
inflammation and can be regarded as a significant prognostic factor, which allows to predict the primary and re-occlusion of
the
vessels
of
the
heart
and
brain
[179,
210].
It was revealed that the level of C-reactive protein as a marker of high risk for stroke convincingly shown in several
prospective
studies
[207].
It was revealed that the independent risk factors for coronary heart disease is increased coagulant activity of factor 7 and the
low plasma fibrinolytic activity, but the sound data on their relationship with stroke so far [168].
According to G. Wannamethee et al., Confirms that even a slight decline in kidney function are at risk of stroke [41, 127,
166,
209].
There is a high degree of correlation of risk for ischemic stroke, and alcohol abuse [150, 164, 167, 192]. However, there are
studies in which it is proved that moderate alcohol consumption has a protective effect on cardio - vascular system, and the
complete
abandonment
of
use
may
have
adverse
effects
[164].
According to most researchers smoking increases the risk of stroke in 2 times. Found that smoking cessation leads to a
significant reduction in risk of death from stroke in the next 2-4 years [145, 165, 167].
Dyslipidemia and hypercholesterolemia, are known to be an important risk factor for coronary artery lesions, while in terms
of communication with ischemic stroke, there are different opinions. Some consider this relationship unproven, although
according to other sources, there is a clear positive correlation between total and HDL-cholesterol and the protective role of
HDL-cholesterol
on
extracranial
carotid
atherosclerosis
affected
[40,
72,
94,
142].
One of the reasons that lead to brain stroke, a rheumatic disease with the development of revmovaskulita cerebral
vessels. Rheumatic fever, affecting mostly young adults, causes a high percentage of disability, early disability and
advancing causes great damage to the patient, his family and society. [2, 3, 28, 34, 68, 76, 77, 79, 84, 117, 124, 148, 171,
174].
The leading place in the pathologic picture neyrorevmatizma take changes of connective tissue structures - mesenchymal
structures of the brain. The defeat of the walls of cerebral vessels leads to secondary changes in the brain parenchyma. Along
with structural changes play a significant role neurodynamic changes in various functional systems of the brain, developing a
second brain parenchymal hypoxia, due to changes in vascular wall and heart failure [3, 34].
When neyrorevmatizme is inflammatory, vascular and degenerative changes in the nervous tissue. One of the most common
forms of cerebral rheumatism is vascular. The pathologic process involves the entire vascular network, revmovaskulity
cerebral vessels often lead to acute and chronic disorders of cerebral circulation (there and hemorrhagic thrombo-arteritis
with
lesions
of
various
sizes
of
brain
tissue)
[148,
171,
174].
It is known that endothelial cells of arteries, destroy and transform the biogenic amines, produce and secrete a polysaccharide
glycocalyx, basement membrane, a number of substances that play an important role in thrombus formation (plasminogen
activator, VIII factor and factor Villibranda, antirombin III, thromboxane B2, and prostacyclin, a warningadhesion of
activated
platelets
to
the
endothelium
and
vascular
wall
provides
tromborezistentnost)
[38].
Aggregates of platelets and fibrin is formed mainly in the areas of endothelial damage, especially in the joints of the
cells. There is reason to believe that the inflammatory changes of the endothelium by local disturbances of coagulation
properties of the vascular wall are the main links of thrombotic complications in rheumatic disease, especially as the vascular
lesions are considered for this affliction is almost mandatory [37, 38, 39, 45, 112, 158].
Slowing of blood flow plays an important role in the thromboembolic process in rheumatism. Violation of myocardial
contractility detect even the absence of clinical signs of heart failure. According to the authors, in patients with rheumatic
heart disease there is a connection between heart failure and the possibility of thromboembolic complications [9, 34, 45, 58,
117].
At the same time, according to other researchers, the direct relationship between the degree of hemodynamic disorders and
the
likelihood
of
thrombosis
and
embolism
is
not
observed
[19,
37].
It is also necessary to emphasize that hemodynamic changes and vascular lesions are usually linked: with increasing degree
of heart failure, damage to arteries increases [3].In addition, the slowing of blood flow associated with intracardiac thrombus
formation processes due to stasis of blood in the cavities of the heart (usually in the left atrium with mitral stenosis) [45].
Definition,
classification,
pathogenetic
mechanisms
and
risk
factors
for
stroke
By a stroke include acute cerebral circulatory disorders, characterized by a sudden (within minutes, at least - hours), the
appearance of focal neurological symptoms (motor, speech, sensory, koordinatornyh, visual disturbances, etc.) and / or of
brain disorders (altered consciousness, headache, vomiting, etc.) that persist for more than 24 hours or leading to death of the
patient
in
a
shorter
period
of
time
due
to
the
causes
of
cerebrovascular
origin.
Stroke is divided into hemorrhagic and ischemic (cerebral infarction). By the nature of the flow and produce a small stroke,
which impaired the function is fully restored within the first 3 weeks of illness. However, such relatively mild cases observed
in
only
10-15%
of
stroke
patients.
Transient ischemic attacks (TIA) are characterized by sudden onset of focal neurological symptoms that develop in patients
with vascular disease (arterial hypertension, coronary heart disease, rheumatism, etc.) and continue for several minutes, at
least - hours but not more than a day and end with full restoration of disturbed features. Transient focal neurologic deficits
with symptoms that have developed as a result of short-term local ischemia of the brain, are also designated as a transient
ischemic attack (TIA). TIA is a special form of acute hypertensive encephalopathy. Most acute hypertensive encephalopathy
occurs in patients with malignant hypertension and clinically severe headache, nausea, vomiting, disturbance of
consciousness, convulsive syndrome in some cases accompanied by focal neurological symptoms. Occurrence of stroke, TIA
or small indicating a high risk of recurrent and, as a rule, more severe stroke (as the pathogenetic mechanisms of these states
are
very
similar)
and
requires
the
prevention
of
recurrent
stroke.
According to conventional classification are the following types of hemorrhages in the brain: parenchymal, - lateral and
medial,
parenchymal,
subarachnoid,
parenchymal,
ventricular,
subarachnoid,
ventricular,
subdural.
Ischemic stroke is divided into the following subtypes (Shtulman DR, Levin DC, 2001): atherothrombotic, cardioembolic,
hemodynamic,
lacunar,
hemorheologic
mikrooklyuziya
Bleeding in the brain often caused by rupture of microaneurysms arising from the defeat of the walls of small arteries under
the influence of prolonged hypertension. Are less likely to cause vascular malformation, hemorrhagic diathesis, vasculitis,
brain tumors, the use of anticoagulants, thrombolytics. For these states is characterized by pronounced focal, cerebral
symptoms,
disorders
of
the
cardiovascular
system
and
respiratory
system.
Subarachnoid hemorrhage in most cases due to rupture of intracranial aneurysms, localized in the circle of Willis. The reason
may also be trauma, intracranial arteries bundle, bleeding diathesis, thrombosis of cerebral veins. At the same time in the
clinic is dominated by pronounced cerebral and meningeal symptoms without focal symptoms.
Parenchymal hemorrhage often occur when arteriologialinoze may occur in the blood supply to both carotid and
vertebrobasilar arteries (but more often in zones of the middle cerebral artery blood flow) and are accompanied by cerebral,
meningeal symptoms and local neurological deficit. Depending on the location relative to the internal capsule, parenchymal
hemorrhage subdivided into medial (inwards from the internal capsule) and lateral (outwards from the internal capsule).
Ventricular hemorrhage characterized by the growth of catastrophic disturbances of vital functions: for a few seconds or
minutes until the mind is disturbed deep coma, there are marked disturbances of respiration, cardiovascular activity, impaired
thermoregulation (sharp pyrexia - more than 41.5 O-42OS .) In most cases the disease ends in a quick death of the patient.
Ischemic
stroke:
A. Atherothrombotic stroke is associated with atherosclerotic lesions of cerebral or precerebral vessels. Atherosclerotic
plaque forms in arteries of large and medium-sized, often in their division into smaller branches. This growing atheroma
narrows the vessel and promotes the formation of a blood clot causing the blockage of the vessel, but a good collateral blood
flow for a long time may even compensate for significant occlusion. Therefore, the immediate cause of ischemia, emboli are
most often formed as a result of separation from the clot fragment thereof. In addition, due to hemodynamic disturbances
affected remote areas, usually located on the border of two vascular blood supply to the basin.
Two. Cardioembolic stroke. The source most often are the thrombotic mass in the left atrium, left ventricle, occurring
during atrial fibrillation, cardiomyopathy, parietal thrombus in myocardial infarction. Also at high risk of embolism in
bacterial
endocarditis,
atrial
myxoma,
with
open
heart
surgery
using
a
heart-lung
machine.
Embolus, blockage of the artery, are often subjected to fibrinolysis, which leads to the restoration of blood flow. However,
due to impaired capillary permeability in the zone of reperfusion there diapedetic hemorrhage, which increases the risk of
hemorrhagic
transformation
Three. Hemodynamic stroke occurs on the background of stenotic lesions rough arteries in a sharp drop in blood
pressure. This causes ischemia of the most remote, the watershed areas. The same condition can occur as a result of hypoxia
associated
with
circulatory
arrest.
4. Lacunar infarcts are associated with the pathology of small cerebral vessels, usually penetrating branches of major cerebral
arteries supplying the deep parts of the brain.The most common reason for them - hypertensive microangiopathy, embolism,
atherosclerotic
place
of
origin
of
these
branches.
Five. Hemorheologic mikrooklyuziya - the cause of a change in the rheology of blood, leading to occlusion of the
microvasculature.
To more accurately identify the type of stroke is recommended during the first hours of stroke to ultrasound, angiography,
ECG monitoring and blood pressure, the study of hemorheological properties of blood. Using modern methods of diagnosis,
it is possible in a timely manner to establish the type of stroke, and, therefore, begin to pathogenetic treatment.
Greater effect with early intensive therapy is associated with the existence of ischemic penumbra zone around the so-called
"nuclear zone". It is shown that the metabolism of oxygen in the most affected in the central area of ischemia and to a lesser
extent, in the demarcation zone. The area of the brain with the most pronounced decrease in blood flow (10 ml per 100 g)
becomes irreversibly damaged very quickly within 6-8 minutes from the time of stroke. This is the nuclear area. Within
hours, the central point is surrounded by ischemic blood flow, but the living tissue (with a decrease in cerebral blood flow to
20 ml per 100 g) - the so-called zone of ischemic penumbra and penumbra. (EI Gusev, Skvortsov, VI et al 1999 .) In the
penumbra in general preserved energy metabolism, and there are only functional but not structural changes. Due to the
penumbra zone of a gradual extension of infarct size. The duration of the penumbra of each individual patient and determine
the boundaries of the so-called therapeutic window within which the most effective therapeutic measures. The formation of
most of the myocardial ends after 3-6 hours of the onset of clinical symptoms of stroke.However, using the most sensitive
histochemical methods revealed that doformirovanie heart attack lasts for 48-72 hours. Thus, treatment of stroke should be
started as early as possible, preferably within the first 3:00 of the disease and it must be the most intense and pathogenetically
directed
in
the
first
3-5
days.
It is extremely important role in ischemic stroke are disorders of metabolic processes in the brain. Ischemia due to decreased
cerebral blood flow leads to an acute shortage of macroergs (creatine phosphate, adenosine triphosphate). Inhibited glucose
utilization by way of aerobic and anaerobic activated, progressive lactic acidosis, which disrupt the function of the enzyme
system that controls ion transport. This pathological process leads to a passive outflow of potassium ions from neurons and
intense influx of calcium ions are sodium and chlorine, as well as intracellular accumulation of free fatty acids and
water. This also contributes to the release of excitatory neurotransmitters during ischemia - glutamate and aspartate [121].
Depending on the degree of ischemia activates the cycle of arachidonic acid with the secondary accumulation of its products
- prostaglandins, thromboxane, which have a negative impact on the system of aggregation of blood elements, in particular
contribute
to
the
intense
platelet
aggregation
[37].
Disorganization of membrane permeability leading to edema of the brain, reducing the level of perfusion, which
subsequently leads to dislocation syndrome with the development of a secondary stem syndrome. Edema - the most common
immediate
cause
of
death
in
patients
with
cerebral
infarction
[33,
39,
90,
92,
137]
To systematize the complex reactions of ischemic cascade may be offered a conditional and a simplified scheme of its
successive stages: 1 reduction in cerebral blood flow, 2 - the local inflammatory response of the brain, 3 - glutamate
excitotoxicity, and 4-intracellular accumulation of calcium, 5 - activation of intracellular enzymes, 6 -increased synthesis of
NO and the development of oxidative stress, 7 - early response gene expression, 8 - swelling of the brain mzga, 9 long-term
effects of ischemia, 10 - apoptosis.
Risk
factors
for
acute
cerebrovascular
Currently,
the
most
important
risk
factors
for
stroke
are:
• Age. For example, in 80 years, the risk of ischemic stroke is 30 times higher than that in 50 years.
• Hypertension. The risk of stroke in patients with blood pressure over 160/95 mm Hg. of Art. increased approximately 4fold compared with people with normal blood pressure, and when blood pressure over 200/115 mm Hg. of Art. - 10 times.
• Diseases of the heart. The most significant predictor of ischemic stroke is atrial fibrillation (atrial fibrillation). In persons
older than 65 years its prevalence is 5-6%. The risk of ischemic stroke is on the increase in 3-4 times. He is also increased in
the presence of coronary artery disease (2 times), left ventricular hypertrophy on ECG (3 times), and heart failure (3-4 times).
• TIA is a significant predictor of both cerebral infarction and myocardial infarction. The risk of ischemic stroke is in patients
with
TIA
and
about
4-5%
per
year.
• Diabetes mellitus. Patients with this disease often have abnormalities of lipid metabolism, hypertension, and various
manifestations of atherosclerosis. At the same time no evidence that the use of hypoglycemic agents in patients with diabetes
reduces
their
risk
of
ischemic
stroke.
• Smoking. Increases the risk of stroke in half. It accelerates the development of atherosclerosis of the carotid and coronary
arteries. Smoking
cessation
results
in
2-4
years
to
reduce
the
risk
of
stroke.
• Oral contraceptives. Preparations containing estrogen for more than 50 mg significantly increased risk of ischemic
stroke. Particularly unfavorable combination of their acceptance of smoking and elevated blood pressure.
• Asymptomatic carotid stenosis. The risk of stroke about 2% per year. It significantly increases in stenosis of the vessel for
more than 70% when a TIA and 13% a year.Occlusive lesions of carotid arteries also serve as a marker of systemic and, in
particular, of coronary atherosclerosis. Such patients often die not from stroke and from CHD.
Many people in the population has multiple risk factors, each of which can be expressed in moderation. For example, a
subject is revealed "mild" hypertension, myocardial hypertrophy, moderate, light diabetes. All areas of prevention focused on
control of risk factors and their correction as the specific people, and in the general population.
Individual risk of stroke, which may be essential in such cases is determined by special scales made on the basis of long-term
monitoring of a large contingent of people. One of the best known is the Framingham scale. It allows us to estimate
individual risk of stroke (in percentage) for the next 10 years and compare it with srednepopulyatsionnym risk for the same
period.
Diagnosis
of
stroke
Computed
tomography
Without the use of contrasting materials to immediately rule out hemorrhage as a cause of focal cerebral blood flow, may
reveal swelling of surrounding tissues and, less reliably, hemorrhagic infarction. Allows you to determine the presence,
extent and localization of supratentorial infarcts, even the size of 0.51 cm This method can not detect the majority of heart
attacks during the first 48 hours and often can not detect damage to the cortex or brain stem.
Magnetic
resonance
imaging
A more informative method for diagnosis negemorragicheskih strokes. A heart attack can be detected within a few hours
after the occurrence, including the localization in the cortex and the posterior cranial fossa. In addition, you may find gaps of
less than 0.5 cm hemorrhagic component is determined by brain infarction, we can get an idea of blood flow in many of
intracranial
arteries.
Angiography
Angiography - is the primary method for diagnosis of vascular lesions. However, all methods of radiation diagnosis, it is
accompanied by the greatest number of complications associated with the introduction of a catheter into the vessel, summing
it to the right place, the introduction of contrast medium and the removal of the catheter.Appointing angiography with
therapeutic or diagnostic purposes, it is necessary to assess the need for this procedure and the degree of risk in pursuing
it. Appointment of a large amount of fluid before and after the study provides a better tolerability of the contrast medium. It
is usually inserted through the femoral artery, and then pressed against the artery to prevent bleeding. After angiography
should carefully check the puncture site and the pulse in the distal artery, so as not to miss a femoral hematoma or emboli.
With
it
you
can:
1) modified to detect ulcerative atherosclerotic plaques, severe stenosis of the vessel wall thrombus formation;
2)
visualize
atherosclerosis,
carotid
siphon,
or
a
bundle
of
intracranial
vessels;
3) to visualize the collateral circulation provided by the circle of Willis vessels (arterial circle of the brain);
4)
reveal
occlusion
of
cerebral
vascular
emboli.
Remains the best method for detecting the basilar artery atherosclerotic disease, but due to the high risk of complications and
the provocation of a new vertebral angiography stroke should be used only when using MRangiografii can not confirm the
clinical diagnosis of basilar artery lesions. Confirmation of this diagnosis affects the patient's treatment. In recent years, CT
and MRI in many cases replaced by this procedure. At present, it carried out to study the small intracranial vessels (eg,
vasculitis,
arteriovenous
malformations,
aneurysms),
as
well
as
endovascular
interventions.
Complications. For angiograms of the aortic arch, carotid and vertebral artery catheter was inserted through the femoral
artery. The most severe complication of cerebral angiography - a stroke caused by embolism of cerebral arteries. Its source
may be a blood clot that has formed at the end of the catheter and a blood clot or piece of atherosclerotic plaque, displaced
catheter, a guide or a jet of contrast medium. The severity and duration of neurological disorders depend on the size of
emboli, its composition (fresh blood clot more easily divided), location, condition of collateral blood flow. This complication
occurs more often when there is insufficient experience of the personnel, atherosclerosis, spasm of cerebral vessels, decreases
cardiac output and blood oxygen capacity and in elderly patients, and possibly migraine. The probability of transient cerebral
ischemia and stroke is 4%, persistent neurological disorders - 1%.Death occurs in less than 0.1% of cases.
If you violate the permeability of the blood-brain barrier, whether due to illness or under the influence of vysokoosmolyarnyh
contrast agents, the latter may cause a neurotoxic reaction. Apparently this is due to the fact that vysokoosmolyarnye
substance as opposed to low osmolarity affect the membrane potentials. In the fusiform aneurysm of the basilar artery during
angiography may develop a reversible lesion of the brain stem fixation and acute amnesia. This is due to slow passage of
contrast medium and longer exposure to the brain. In rare cases, the introduction of contrast material under high pressure is
possible
cerebral
artery
aneurysm
rupture
with
subarachnoid
hemorrhage.
The method of duplex scanning or DS combines ultrasound, which allows to direct visual assessment of the vessel and the
use of Doppler techniques for the detailed assessment of the lumen and blood flow. During the procedure, in real time is the
construction
of
the
spatial
two-or
three-dimensional
images
of
the
lumen.
The method of duplex scanning to evaluate the state of vascular walls and lumen, and the dynamics of their environment as a
whole, it is possible to visualize organs, tissues, blood vessels at the same time obtaining the Doppler spectrum of blood
flow. The method of duplex scanning is invaluable for deep-seated need to examine the major blood vessels or detect
obstruction
of
peripheral
thrombosis.
The
method
of
duplex
scanning
can
identify:
Stenotic
and
occlusive
vascular
pathology
of
the
brain
The
presence
of
thrombosis
and
stenosis
Lack
of
perforatnyh
veins
Congenital
anomalies
of
the
veins
and
arteries
Physiological
disorders
of
blood
flow
in
vessels
Spare
capacity
of
the
cerebral
circulation
The
structure
of
the
walls
of
any
vessel,
the
lumen
patency
and
Turn
the
vessel
into
the
tissues
(bends,
deformation,
malformation,
etc.)
Abnormal
formation
of
the
brain
and
their
effects
on
blood
vessels
Duplex scanning is indispensable for postoperative control after vascular bypass operations and, monitoring of
patients
after
stroke.
The method of duplex scanning (DSSG) combines the ability to see the major brain structures (including walls of blood
vessels and surrounding tissues) and blood flow in arteries and veins of the head and neck. Currently, the most modern
method the most accurate diagnosis of disorders of cerebral circulation. Duplex scanning of the brain vessels includes two
research
basins:
extracranial
vessels
(neck)
and
transcranial
(intracerebral)
vessels.
With duplex scanning may not only detect pathology of cerebral circulation (eg, atherosclerosis, congenital malformations,
tortuosity, and constriction and spasm of blood vessels), but the primary screening diagnosis in early childhood tumors, cysts,
hematomas, foci of stroke, blood supply to the assessment data structures. At the same stress tests can accurately assess the
functional
status
of
cerebral
circulation.
The method has no contraindications and requires no special preparation of the patient for the study.
USDG
cerebral
Non-invasive and reliable method of diagnosis is the Doppler method. With this method it is possible to study the speed and
volume blood flow, to study the degree of regulation of cerebral circulation disorders. According angiogpaficheskih
patomopfologicheskih and research in the pathogenesis of ischemic diseases of the brain in half the cases the main ROLE
igpaet popazhenie ekstpakpanialnyh departments magistpalnyh aptepy head. For an accurate determination of the location
and extent Prevalence okklyuzipuyuschego ppotsessa need tsepebpalnaya angiogpafiya. However, it represents SOME pisk
for the patient, special tpebuet dopogostoyaschey appapatupy and can not be put into practice everywhere, so it is highly
relevant is pazpabotka safe and readily available diagnostic vascular lesions of the head. One such method is the use of
Doppler ultrasound to effect Dopplepa allowing register the change in speed of the pulsating flow in the vessels kpovi chepez
nepovpezhdennuyu
skin.
For the detection of carotid okklyuzipiyuschih popazheny aptepy the cord combined study kpovotoka in the total, internal,
external carotid and branches of the ophthalmic aptepiyah aptepii. The most frequently found in atherosclerotic lesions of the
internal carotid artery.
Symptoms
of
stenosis
of
the
ICA
1) Reduced BFV in general or internal carotid artery by 30% or more compared with the contralateral arteries.
2)
Reduction
of
diastolic
blood
flow
in
the
common
carotid
artery.
3) Reduced BFV in the supratrochlear artery by 40% or more compared to the other.
4) The appearance of retrograde blood flow in the supratrochlear artery compression for 2-4 seconds homolateral common
carotid
artery.
5) Reduced BFV in the supratrochlear artery with compression of the front or the superficial temporal artery in the face on
the
side
of
the
study.
6) Change the retrograde blood flow in the supratrochlear artery Antegrade direction in response to compression of the
superficial
temporal
artery
of
the
same
name.
Signs
of
the
internal
carotid
artery
occlusion
1) Blood flow in the internal carotid arteries are not registered or are now experiencing severe (more than 30%) of BFV
asymmetry
in
the
common
carotid
arteries.
2)
The
supratrochlear
artery
is
determined
by
the
retrograde
blood
flow.
3)
Blood
flow
in
the
supratrochlear
artery
is
not
defined.
4) Record the physiological (antegrade) blood flow in the supratrochlear artery, is not reduced by clamping for 2-4 seconds
ipsilateral
(homolateral)
of
the
common
carotid
artery.
Doppler sonography examination, conducted in acute ischemic stroke, helps to clarify the level of destruction of the vascular
system (arteries of the head, base of the brain arteries, the small intracranial arteries), to assess the functional status of
cerebral blood flow (conservation of the main stream, the presence of hyperperfusion, hypoperfusion, obstructed perfusion
preservation
of
autoregulation )
and
to
predict
the
outcome
of
the
disease.
As a result of Doppler examination of patients with acute ischemic stroke in the carotid arterial hypertension, cerebral
arteriosclerosis, diabetes and rheumatic fever has been allocated seven major variants of blood flow in acute ischemic stroke:
a - the main symmetrical blood flow in middle cerebral artery (MCA) 2 - thrombosis of the MCA or its major branches, 3 asymmetry of blood flow in the MCA with a decrease in BFV on the side of a heart attack and preservation of the main
stream type, 4 - hyperperfusion in the MCA on the side of a heart attack, 5 - residual blood flow in the proximal MCA in the
presence of hemodynamically significant lesion located ICA, 6 - stenosis of the intracranial arteries, 7 - Difficult perfusion on
the background of increased intracranial pressure. Save symmetric or asymmetric main types of blood flow was observed
predominantly in small cortical and lacunar infarcts in the background of high systemic blood pressure with good recovery of
neurological deficit. When combined within atherosclerotic hypertension and diabetes observed difficulty in the carotid
perfusion.Vasospasm of cerebral vessels was observed mainly in the cardioembolic ischemic stroke of rheumatic etiology.
Brief
clinical
characteristics
of
ischemic
stroke
Transient
ischemic
attack
(TIA). Manifested
focal
neurological
impairment,
which
completely
disappears
within
24
hours
Can
be
divided
into
three
etiologic
categories:
1)
TIA
associated
with
slow
blood
flow
in
large
vessels;
2) the embolic TIA, and 3) lacunar, or caused a violation of penetrating the blood flow in vessels. TIA associated with a
slowing of blood flow, usually short-term (minutes to hours), are prone to relapse, and stereotyped. Any obstructive process
in non-or intracranial arteries can cause a TIA due to slowing of blood flow, if the collateral blood flow in the ischemic area
as disturbed. Embolic TIAs are characterized by longer duration of focal neurological symptoms (hours). Lacunar TIAs occur
because of temporary cerebral ischemia resulting from stenosis of intracerebral penetrating vessels, usually in secondary
lipogialinoze against hypertension or with atherosclerotic stenosis. It is believed that recurrent stereotypic TIAs or lacunar or
TIA are associated with the violation of the blood flow in small vessels. Other causes of transient neurologic disease
(convulsive manifestations or migraine) should be excluded on the basis of medical history and appropriate examination.
Completed stroke. A condition in which a few days the patient is not marked increase in neurologic symptoms.
Ischemic stroke. Neurological impairment caused by circulatory disturbance of the brain region for intravascular
occlusion or slow flow. He suffers from brain region that receives blood supply from the affected vessel.
Ischemic
stroke
can
be
caused
by:
1)
a
large
vessel
thrombosis,
caused
by
slow
blood
flow;
2)
arterioarterialnoy
embolism,
cardiogenic
or
unknown
origin;
3)
the
formation
of
gaps
due
to
occlusion
of
small
intracerebral
penetrating
vessels.
The major subtypes of ischemic stroke are as follows: atherothrombotic (34%), cardioembolic (22%), hemodynamic (15%),
lacunar (20%) and stroke by type of hemorheological mikrooklyuzii (9%). Cerebral infarction can occur in various parts of
the brain and its localization in the main blood supply to the circuit corresponds to the large vessels. The most common
(75%), heart attacks occur in the middle cerebral artery, at least - heart attacks and vertebrobasilar (20%), while in the pool
anterior
cerebral
artery
are
observed
only
5%
of
cases.
Clinic
for
ischemic
stroke.
Ischemic stroke usually develops within a few seconds or minutes (sometimes for hours or days) and appears to
motor, speech, and (or) other focal neurologic disturbances. Disorders of consciousness, vomiting, intense headache in most
cases is not observed, except for heart attacks in the brain stem, cerebellum, or large hemispheric infarcts. Ischemic stroke
often occurs during sleep or after sleep, but it can also occur during exercise, taking a hot bath, drinking alcohol, emotional
stress,
or
without
any
precipitating
factors.
The progressive course of stroke or stroke in the development (gradual or step-like increase of neurological
disorders in a few hours or days) was observed in 20% of patients with ischemic stroke in the carotid and 40% of patients
with ischemic stroke in the vertebrobasilar basin. It is usually caused by an increase in the size of intra-arterial thrombus,
recurrent embolism, the growth of brain edema, hemorrhagic transformation of infarction or increasing its size by reducing
systemic blood pressure. In cases where the neurological disorders are stable or gradually regress, stroke is considered as
completed.
High blood pressure is observed in 70-80% of patients in the early days of a stroke. High blood pressure often seen
in the early days of ischemic stroke is not only in patients with hypertension, but also in individuals who have not seen the
rise of blood pressure to stroke. In the future, most of it is marked spontaneous decline. Transient increase in blood pressure
may be caused by brain edema and increased intracranial pressure, and stress caused by the development of severe illness and
emergency admissions, a violation of autoregulation of cerebral blood flow, increasing levels of norepinephrine in the blood
serum. The rise in blood pressure may be an adaptive response aimed at increasing cerebral blood flow in the area of cerebral
ischemia.Increased blood pressure during hospitalization is regarded as a favorable prognostic sign of the outcome of
ischemic stroke, although the persistence of high blood pressure during the day is not associated with a favorable outcome of
stroke.
Stroke in the carotid system, there are 5-6 times more frequently than in the vertebrobasilar basin. They usually
develop motor and (or) sensitive violations on one side and (or), aphasia (with lesions of the dominant hemisphere),
anosognosia and impaired body schema (in the subdominant hemisphere lesions). Sometimes it is also observed
homonymous
hemianopsia.
The syndrome of total defeat in the carotid region consists of contralateral hemiplegia, unilateral anesthesia, paresis of the
facial muscles and tongue, hemianopsia, aphasia, or anosognosia. Sometimes there is paresis of horizontal gaze toward
diverting eyeballs towards the hearth. The development of this syndrome is usually caused by occlusion of the main trunk of
the middle cerebral artery (usually embolus) or internal carotid artery (thrombus often sometimes with spread it in the middle
cerebral artery).Hemiplegia, unilateral anesthesia, paresis of the facial muscles and tongue may occur with occlusion of the
deep branch of the middle cerebral artery supplying the internal capsule and basal ganglia.
Syndromes of the partial destruction of the carotid system, often caused by occlusion of the middle cerebral artery
branches (mainly embolus) or internal carotid artery (usually a clot) or narrowing of their (usually atherosclerotic):
hemiparesis with a predominance in the hand or arm monoparez, paresis of the facial muscles and tongue of central type , or
gemigipesteziya monogipesteziya hands verhnekvadrantnaya hemianopsia, etc. Any damage to the dominant hemisphere can
be observed in isolation (or in combination with motor and sensory disturbances in the extremities) disorders of higher
mental functions - motor aphasia, sensory aphasia, total aphasia, alexia, agraphia, acalculia and etc.
The combination of symptoms brain and monocular blindness (retinal ischemia) on the one hand pathognomonic for
occlusive lesions of the internal carotid artery. Less common symptoms of anterior cerebral artery lesions, which usually
occur contralateral hemiparesis with a predominance in the leg or foot monoparezom. Sensory disorders at the same time are
rare
and
usually
mild. Sometimes
there
wrong
behavior,
agitation
and
urinary
incontinence.
Strokes in the vertebrobasilar system may appear homonymous hemianopsia, oculomotor disturbances, bilateral
impaired movement or sensation in extremities, cerebellar ataxia and nystagmus, alternating classical syndrome - damage to
one or more cranial nerves on the one hand, combined motor and (or) sensitive to disturbances in the extremities On the other
hand. There are also violations of higher brain functions such as sensory aphasia and agnosia. Vertigo only in conjunction
with nausea, vomiting, horizontal or rotatory nystagmus, in rare cases it may be a manifestation of stroke in the
vertebrobasilar
system,
but
more
often
due
to
another
cause
(eg,
vestibular
neyronitom).
Wallenberg's Syndrome, Zakharchenko - one of the most common variants of stroke in the vertebrobasilar system. It is
caused by the defeat of dorsal-lateral medulla and cerebellum and in the classic version includes dizziness, nausea, vomiting,
hypoesthesia person, cerebellar ataxia and Horner's syndrome on the affected side, hypoesthesia of limbs and trunk on the
opposite side, nystagmus, impaired swallowing (dysphagia) hoarseness (dysphonia). However, there are more variants of the
syndrome with no or minor lesions of the medulla oblongata, which are manifested primarily dizziness, ataxia, and
nystagmus. In most cases, Wallenberg's syndrome, caused by blockage of Zakharchenko (thrombus or embolus) or lower
vertebral
posterior
cerebellar
artery.
Rapid disturbance of consciousness, oculomotor disturbances, tetraplegia characteristic of basilar artery occlusion, which
usually ends in death. Different syndromes can occur when blockage (thrombus or embolus) branches of the basilar artery: a
peripheral paresis of the facial muscles and contralateral hemiplegia syndrome (Miyyara-Gyublera-Zhyuble), oculomotor
nerve palsy with contralateral hemiplegia (Weber syndrome) or gemiataksiey syndrome (Benedict), gaze palsy up and
convergence palsy (Parinaud's syndrome) and other homonymous hemianopsia alone or in combination with unilateral
anesthesia on the same side, as well as visual (cortical), agnosia, and often caused metamorfopsii occlusion (thrombus or
embolus), posterior cerebral artery, which in lesions of the dominant hemisphere can lead to sensory aphasia and
alexia. Hemianesthesia with giperpatiey, ataxia, with a gradual accession of pain in the affected limbs are characteristic of
thalamic lesions, which may arise as a result of the defeat of both the vertebrobasilar and carotid systems.
BASIC
Pathogenetic
(NV
Atherothrombotic
A. Home
-
CRITERIA
SUBTYPE
Vereshchagin
often
stroke
intermittent,
(including
step-like,
OF
Ischemic
et
with
DIAGNOSIS
Stroke
2000)
al.,
the
a
arterio-arterial
gradual
increase
in
embolism)
symptoms
for
hours
or
days. Often
debut
during
sleep.
Two. The
presence
of
atherosclerotic
lesions
of
extra-and
/
or
intracranial
arteries
(Expressed
constrictive,
occlusive
process,
atherosclerotic
plaque
with
a
rough
surface,
with
the
adjacent
thrombus),
respectively,
patchy
lesion
in
the
brain.
Three. Often
preceded
by
ipsilateral
transient
ischemic
attack.
4. The
size
of
the
lesion
can
vary
from
small
to
extensive.
Cardioembolic
stroke
A. Home
usually
sudden
onset
of
neurological
symptoms
in
awake,
active
patient. Neurological
deficit
as
expressed
in
the
opening
the
disease.
Two. Localization
primarily
vascularized
area
of
the
middle
cerebral
artery.
Heart
attack
most
medium
or
large
cortico-subcortical. Characterized
by
the
presence
hemorrhagic
component
(by
CT
of
the
head).
Three. Anamnestic
indication
and
CT
signs
of
multiple
focal
lesions
of
the
brain
(in
including
the
"silent"
cortical
infarcts)
in
different
basins,
which
are
not
areas
the
adjacent
blood
supply.
4. The
presence
of
cardiac
disease
the
source
of
embolism.
Five. The
absence
of
gross
atherosclerotic
lesions
of
the
vessel
proximal
to the obstruction of intracranial arteries. The symptom of "vanishing occlusion" with dynamic
angiographic
examination.
6. In
history
Thromboembolism
other
organs.
Hemodynamic
stroke
A. Home
sudden
or
step-like
current
active
patient
and
at
rest.
Two. Localization of the hearth - a zone adjacent blood supply, including cortical infarcts, foci of
in
the
paraventricular
white
matter
and
semiovalnyh
centers. Infarct
size
from
small
to
great.
Three. The
presence
of
pathology
of
extra-and
/
or
intracranial
arteries:
Atherosclerotic
lesions
(multiple,
combined,
en
echelon
stenosis),
Deformation
of
the
artery
(angular
bends,
looping)
- Abnormalities of the vascular system of the brain (the circle of Willis uncoupling, hypoplasia of the arteries).
4. Hemodynamic
factors:
- Lowering blood pressure (physiological
- during sleep, as well as orthostatic, iatrogenic
hypotension,
hypovolemia)
Drop
in
cardiac
output
(stroke
volume
decrease
due
to
myocardial
ischemia,
a
significant
slowing
of
heart
rate).
Lacunar
stroke
A. Prior
hypertension.
Two. Home
often
intermittent,
symptom
increases
within
hours
or
days. BP
is
usually
increased.
Three. Localization of a heart attack - the subcortical nucleus accumbens white matter semiovalnogo
center, internal capsule, the base of the bridge of the brain. The size of the hearth - a small, up to 1 to 1.5 cm in
diameter,
and
may
not
be
visualized
on
CT
of
the
head.
4. The
presence
of
characteristic
neurological
syndromes
(pure
motor,
pure
sensitive
lacunar
syndrome,
atactic
hemiparesis,
dysarthria,
and
monoparez;
Isolated
monoparez
hands,
feet,
face
and
other
syndromes). Lack
of
brain
and
meningeal
symptoms,
and
disorders
of
higher
cortical
functions
in
the
localization
dominant
hemisphere. The
course
often
by
the
type
of
small
strokes.
Stroke
type
hemorheologic
mikrookklyuzii
A. The
minimum
severity
of
vascular
disease
(atherosclerosis,
arterial
hypertension,
vasculitis,
vasculopathy).
Two. Having pronounced hemorheological changes, disturbances in the hemostatic system and the
fibrinolysis.
Three. Marked
dissociation
between
clinical
(mild
neurological
deficits,
the
small
size
of
the
hearth)
and
significant
hemorheological
disorders.
4. Course
of
the
disease
according
to
the
type
of
small
strokes.
Acute
hypertensive
encephalopathy
A. More
often
develops
in
patients
with
malignant
hypertension.
Two. Clinical
manifestations:
sudden
headache,
nausea,
vomiting,
impaired
consciousness,
convulsions.
Three. In
ophthalmoscopy
reveals
papilledema,
angioretinopatiyu.
4. CT of the head - the expansion of the ventricular system, reduced the density of white
substances.
Five. The
intracranial
presence
of
elevated
hypertension,
CSF
pressure
according
at
to
lumbar
liquor
puncture
and
signs
ehoentsefaloskopii.
The course and outcome of stroke is determined by the location and volume of cerebral infarction, the severity of
brain edema, as well as the presence of concomitant diseases and / or development of complications during stroke
(pneumonia, bedsores, urosepsis, etc.). In the first 30 days after stroke kills about 20% of patients. Mortality is higher in the
atherothrombotic and cardioembolic stroke, and is only 2% for lacunary stroke. The cause of death in half the cases - brain
edema and compression of the trunk, in other cases - pneumonia, heart disease, pulmonary embolism, renal failure, or
septicemia. A significant proportion (40%) of deaths occur in the first 2 days after illness and is associated with extensive
edema was hardly a heart attack and brain. Of the survivors of about 60-70% of patients have disabling neurological disorder
by the end of the month after stroke. In cases where neurological disorders regress during the first three weeks (2-21 days),
the disease saw as a small stroke. 6 months after stroke, disabling neurological disorders remains at 40% of surviving patients
at the end of the year - 30% of patients. The more significant neurological deficit at the end of the first month of the disease,
the less likely a full recovery. Recovery of motor function is most important in the first 3 months after stroke, when the
function is often restored foot better than the function of the hand. The complete absence of hand movements by the end of
the first month of the disease is a poor prognostic sign. After a year of stroke recovery of lost neurological function is
unlikely, although the improvement of speech in patients with aphasia may persist for several years after a stroke. In general,
patients
with
lacunar
stroke
indicated
a
better
recovery
than
in
other
types
of
stroke.
Survival of patients after ischemic stroke is approximately 65% by the end of the first year of the disease, 50% 5 years after stroke, 25% - 10 years after a stroke.To bad prognostic sign of survival in the first 5 years after stroke include
older age of the patient, prior myocardial infarction, atrial fibrillation, previous stroke, congestive heart failure. Repeated
ischemic stroke occurs in approximately 30% of patients during the period of 5 years after the first stroke. The frequency of
cerebral infarction is about 5% per year. However, the most common cause of death after stroke - heart disease.
Treatment
of
stroke
Modern
principles
of
treatment
of
ischemic
stroke
The main directions of AI treatment are based on current understanding of the pathogenesis of acute cerebral ischemia and
the choice of adequate drug therapy is a complex task. Significance in the choice of therapeutic tactics is the concept of
heterogeneity of ischemic stroke. Given that acute cerebral ischemia leads to a chain of pathologic processes that cause
changes in neuronal structures, astrocytes, microglial activation and ultimately disruption of trophic brain is most justified
the simultaneous implementation of integrated activities that enhance the perfusion of the brain (improvement in cerebral
blood flow and blood rheology) with neuroprotective therapy [20, 21, 48, 92, 103, 114, 125].
It is proved that one of the most important criteria for predicting the outcome of stroke is reduced and rapid stabilization of
blood pressure. Many drugs used to lower and stabilize blood pressure do not always meet the requirements of pathogenic,
are assigned to these drugs (reserpine, gemiton, magnesium sulfate) [36, 59, 60, 90]. In a clinical study has been proven
ineffective IMAGES magnesium sulphate in ischemic stroke [60]. At the same time, the FAST-MAG study shows the safety
of
magnesium
sulfate
in
pre-hospital
treatment
of
AI
[92].
It should be noted, according to the latest version of the international recommendations for the management of acute stroke
period, leaders of the European Stroke Initiative (EVSI) and the American Stroke Association, the only medical intervention
for the treatment of acute ischemic stroke is thrombolytic therapy with recombinant tissue plasminogen activator (rTAP)
[59].
The analysis carried out by a group of six international experts confirmed the initial findings of a high level of the index of
probability of good outcome of ischemic stroke in the application rTAP [135, 158]. It should be noted that patients who
developed AI rTAP effective when administered within the first 3 hours after onset of symptoms [114, 182].
Treatment includes OZI base and differentiated treatment. Basic therapy is carried out immediately after receipt of the patient
in a hospital and does not depend on the nature of the OZI includes activities aimed at the normalization of respiratory
function and oxygenation, maintenance of systemic hemodynamics, control and regulation of hemostasis, control of cerebral
edema, prevention and treatment of infectious complications. Measures for the prevention of infectious complications include
breathing exercises, suctioning the upper airway, exercise, massage, turning the patient every two hours, the organization of
adequate
nutrition,
in
some
cases
the
use
of
antibacterial
agents.
Differentiated therapy is used only after the nature of the stroke, confirmed by the methods neyroviazualizatsii. In ischemic
stroke, it includes: thrombolytics, antiplatelet agents, anticoagulants, vasoactive drugs, antihypertensive agents, and
hemodilution, except this differential treatment depends on the pathogenic subtypes of ischemic stroke. Patients with
hemorrhagic stroke, along with surgical treatment is prescribed neuroprotectors, anti-therapy, antihypertensive drugs and
drugs
that
reduce
vascular
permeability.
Prophylactic use of antibiotics used to prevent infectious complications, is part of the basic treatment of ischemic and
hemorrhagic strokes. The most common antibiotic therapy is prescribed to prevent nosocomial pneumonia in this group of
patients. From the data in the literature is known about the high frequency of use of antibacterial drugs OZI patients, for
example, the results of large-scale epidemiological study in St. Petersburg showed that antibiotic therapy received 40.6% of
patients
with
ischemic
stroke
and
56.7%
with
hemorrhagic.
In the literature there is no single point of view on the appropriateness of prophylactic antibiotics for OZI. Some authors
believe that antibiotics should be of a preventive nature, especially in severe stroke, swallowing disturbances, coma, or in
patients receiving high doses of glucocorticoids [5, 16, 17]. Other authors do not recommend the use of antibiotics for the
prevention and assign them to offer only the development of infectious complications, including pneumonia [27].
Undifferentiated
treatment.
Patients with acute stroke should be immediately taken to the hospital. The optimal timing are the first 1-3 hours after the
onset of the disease, although the treatment is effective and reasonable in the later period. At this stage, the most desirable is
the hospitalization of the patient in a multidisciplinary hospital with modern diagnostic equipment, including CT or MRI,
tomography and angiography, which also has angionevrologicheskoe Department of ICU and emergency department with a
specially selected unit (beds), and trained personnel to conduct these patients. An indispensable condition is the presence in
the neurosurgery department of a hospital or a team of neurosurgeons, because about one-third of patients in need of advice
or the provision of this type of specialized care. Being in such clinics significantly improves the outcome of stroke and
efficacy
of
rehabilitation.
Emergency
measures
at
admission:
A. Providing the necessary level of oxygenation by clearing the airways, putting duct or even on the testimony of transfer of
the
patient
to
mechanical
ventilation.
Two. Maintenance includes hemodynamic monitoring of blood pressure and heart deyatelnosti.Arterialnoe pressure is not
recommended immediately to reduce by more than 10% because of stroke is disturbed autoregulation of cerebral blood flow
and cerebral perfusion pressure may drop sharply in the fall in blood pressure, leading to secondary hypoxia in brain
tissue. Antihypertensive therapy is conducted with care in small doses of calcium antagonists, beta-blockers (obzidan,
atenolol, etc.) or blockers of the angiotensin-converting enzyme (renitek, etc.) do not cause significant changes in the
autoregulation
of
cerebral
blood
flow.
Three. In cortico-subcortical centers, and break the blood into the ventricular system is often observed bouts of
seizures. Relief of them also is necessary before the neurological examination, as they are difficult to deplete the brain's
neurons. For this purpose, use relanium, injected intravenously. In severe cases, use of sodium thiopental.Further, such
patients
should
immediately
start
prophylactic
long-acting
anticonvulsants
(finlepsin,
etc.).
4. Correction of local inflammatory reactions of the brain and damages the blood-brain barrier. Experimental studies on
models of ischemic stroke have shown the importance of "long-term effects of ischemia" in the mechanisms of formation of
cerebral infarction and in post-stroke progression of atherosclerosis and vascular entsefalopatii.Zapusk and deployment
process of delayed neuronal death induced by activated microglia, which in conditions of ischemia begins to secrete
potentially neurotoxic mediators inincluding proinflammatory cytokines, and initiate the cytotoxic effects of
astrocytes.Proinflammatory cytokines - interleukin (IL), 1,6,8, tumor necrosis factor  (TNF-) effect on the endothelium of
blood vessels, increasing its aggregation properties trigger the migration of leukocytes (initially polymorphonuclear
neutrophil nuclei, and then macrophages) from the vasculature in the ischemic tissue the brain. This leads to the development
of local inflammation in the ischemic focus, microcirculatory disturbances and damage to the blood-brain barrier. Astrocytes
under the influence of proinflammatory cytokines (IL-1, IL-6) increase the synthesis of proteins ostrofaznyh class 1 (Creactive protein and compliment factors) that act as protease inhibitors, growth factors. Experimentally shown that the
severity of inflammatory responses is determined not only by increased production of inflammatory cytokines, including
neytrofinov (IL-10, IL-4, transforming growth factor  - TRF-, etc.). The experimental and clinical studies (Saidvaliev FS,
2005) have shown that the local inflammatory response to brain dysfunction and the structure of the blood-brain barrier are
not unique to ischemic brain damage, and bleeding, and in the latter case, their intensity is several times higher than that for
cerebral ischemia. In this regard, was conducted clinical and experimental study of the influence of a number of non-steroidal
anti-inflammatory drugs on the course of ischemic and hemorrhagic strokes with histology (when the experiment),
instrumental (CT scan in the dynamics), biophysical (calcium-dependent blood coagulation, blood viscosity) and biochemical
(content interleukins and C-reactive protein in the cerebrospinal fluid) verification. Experimental and clinical application
dikloberla (diclofenac sodium) in acute ischemic stroke demonstrated the most effective result. Given that diclofenac
significantly alters the coagulating properties, with hemorrhages in the brain of its effectiveness in the experiment was lower
than during ischemia. Experimental study showed that the most efficient and effective drug for intracerebral hemorrhage is
nimesil
(nimesulide).
Five. Correction of endothelial dysfunction and hemostatic disorders. In recent years, experimental studies conclusively
prove the existence of reciprocal relationships between endothelial factors and intravascular coagulation, as well as their
relationship to electrolyte homeostasis. In the acute stage of ischemic stroke, the active influx of calcium ions in smooth
muscle cells of blood vessels leads to hypertension and vascular spasm, and also leads to destabilization of vascular
endothelial
function
with
a
pronounced
procoagulant
formation
of
prostaglandins.
Depending on the degree of ischemia activates the arachidonic acid cycle with the accumulation of secondary products,
which have a negative effect on vascular tone. It is proved that the level of vascular tone in health and disease, and
determined by the balance of constrictor factors dilatatornyh endothelial nature. The clinical study (NU Abdullaev, 2005)
have shown that the genesis of hypertensive ischemic strokes are characterized by an increase in von Willebrand factor
activity in serum, increased platelet aggregation, reduced fibrinolytic activity of blood and antiagregatsionnoy activity of the
vascular wall. For the correction of endothelial dysfunction, normalization of cerebral hemodynamics and prevention of
vasospasm to the combined use of calcium channel blockers and inhibitors of the enzyme angiotenzinprevrvschayuschego.
6. In ischemic stroke is recommended to perform panarteriografii arteries of the head or arteriography on the affected side of
the brain. In identifying the occluded arteries supplying the brain, the question of thrombolytic therapy.
In addition, regardless of the nature of stroke in the acute period necessary to carry out the following activities:
Continuous
monitoring
of
key
parameters
of
homeostasis
- Control of swallowing (dysphagia in the presence of a nasogastric tube is placed to prevent aspiration pneumonia and to
ensure
adequate
nutrition
patient)
- Monitoring of bladder, bowel, care for the skin. Necessary to conduct the first hours of passive exercises and massage of
hands and feet as an indispensable and the most effective prevention of the condition of one of the main causes of mortality
in stroke - pulmonary embolism (PE), as well as pressure sores and contractures early post-stroke.
- It is important to prevent secondary hemorrhage in the necrotic tissue, which is usually observed in the 1-10th day, and
often is a consequence of uncontrolled blood pressure and reperfusion (mainly thrombolytic) therapy conducted without
contraindications
to
it.
The basis for specific therapy in ischemic stroke are the two strategic areas: reperfusion and neuronal patronage, aimed at the
protection of weak or barely functioning, but still viable neurons, which are located around the hearth infarction (area of
"ischemic
penumbra").
Reperfusion can be achieved through thrombolysis, vasodilation, increased perfusion pressure and improved blood rheology.
Thrombolytic
therapy
The main cerebral thrombolytic recognized urokinase, streptokinase, and their derivatives, as well as tissue plasminogen
activator (tPA). Their use is recommended only after a CT scan and angiography within the first 3 hours (!) From the onset of
stroke in a dose of 0.9 mg / kg body weight intravenously, with small foci on the CT scan and blood pressure no higher than
190/100 mm Hg. Article., the absence of a history of stroke, ulcers, etc. Thrombolytic therapy restores blood flow and is
currently
the
most
effective
treatment
for
ischemic
stroke.
Vasodilators
Drugs such as cavinton, instenon, nicergoline are widely used in clinical practice, but their effectiveness is still being studied.
The
increase
in
cerebral
perfusion
pressure
and
improved
blood
rheology
One of the most popular methods used for this purpose - hemodilution. It is based on two principles impact on the
microcirculation of ischemic brain: blood viscosity reduction and optimization of circulatory volume. It is advisable to carry
out low molecular weight dextran hypervolemic hemodilution (reopolyglukine, reomakrodeks, etc.) only if the hematocrit
level of the patient exceeds 40 units, in providing its volume reduced to 33-35 units. Also, to improve the hemorheological
properties
of
blood
are
used
trental
(200
mg
kapelno2
times
a
day),
and
albumin.
Antiplatelet
Aspirin is an effective proven treatment for the acute period of cerebral infarctions.Perhaps its application in two ways - by
150-300 mg or low doses of 1 mg / kg body weight daily. The feasibility of using antiplatelet agents in the acute phase of an
action,
including
ticlopidine,
and
dipyridamole
(CURANTIL),
is
still
being
studied.
Anticoagulants
of
direct
action
Direct anticoagulant recommended for use in progressive stroke, carotid bundle, or vertebral arteries, the early secondary
prevention of cardiogenic embolism. Heparin prevents the expansion of infarction, which is due to the ongoing thrombosis or
embolization of distal branches. Recommended dose regimen of 5-10 thousand units daily every 4-6 hours for 4-6 days under
the control of blood clotting time.Contraindications to heparin: a rapid uncontrolled rise in blood pressure, coma, septic
embolism, renal and hepatic failure, peptic ulcer and duodenal ulcer, bleeding diathesis.
Neuroprotection
At the present time is allocated a range of drugs, possessing neuroprotective properties postsynaptic glutamate antagonists,
inhibitors of presynaptic glutamate (lubelozol), calcium channel blockers (nimodipine, kaltsibindin, Norvasc), antioxidants
(emoksipin, L-tocopherol), nootropics (piracetam, Cerebrolysin) and others. The feasibility of their use proved in
experimental
conditions.
Surgical treatments for heart attacks cerebellum on a background of acute obstructive hydrocephalus, as well as drainage of
the ventricles of the brain are currently used with high efficiency. The feasibility of other surgical interventions in acute
ischemic
stroke
requires
additional
evidence.
The
role
of
cerebral
edema
in
the
development
of
secondary
ischemic
stroke
with
Pathological processes of the role of edema and swelling of the brain lies in the fact that they increase and (or) cause
compression and displacement of brain structures, creating intracranial hypertension, blood circulation, metabolic processes
and the functioning of the brain during the difficult period of post-traumatic stress and increase mortality in
survivors. Oseltamivir important issues that prevent the development of edema and swelling of the brain, are the following:
provision of adequate cerebral blood flow and gas exchange, the elimination of water and salt, and acid-base state, the
normalization
of
the
permeability
of
blood
vessels.
The classic definition of I. Klatzo, Brain edema is an abnormal accumulation of fluid associated with an increase in the
volume of the brain [70]. According to N.Kvitnitskomu-Ryzhov, excessive accumulation of fluid in the brain tissue is treated
as edema - swelling of the brain. When swelling occurs accumulation of fluid in the intercellular spaces, and swelling of the
brain is an independent process, which is based on the strong binding of water to intracellular biocolloids [11]. Thus, cerebral
edema should be considered as an extracellular and intracellular hydration swelling of both. Most often there is a
combination
of
edema
and
swelling
of
the
brain.
In the foreign literature to highlight the cytotoxic and vasogenic edema of the brain, which can to some extent, be identified,
respectively,
with
swelling
and
edema
of
the
brain.
In the pathogenesis of edema-swelling of the brain are also involved and other factors: systemic arterial pressure, central
venous pressure (CVP), cerebrovascular resistance, blood volume in the vessels of the brain, the rheological properties of
blood and the osmotic pressure, changes in gematentsefalicheskom barrier (BBB). Processes that cause reperfusion injury,
are also activated pool of polymorphonuclear leukocytes, release of proinflammatory cytokines and the formation of
prostanoids
in
aggregate
form
in
the
zone
of
myocardial
inflammation
[5,12,41,97].
At present we know two basic mechanisms of cell death described by K. Vogt (1842) and R. Vihrova (1859) - necrosis, and
the process of active cell death programirovannoy - apoptosis, founded in 1972 by British scientists JFR Kerr, A. Wyllie and
A.R. Currie [69]. The term 'apoptosis' is derived from Greek and means "separation", "falling of leaves from a
tree." Moreover, it should be noted that the very seasonal shedding of leaves (as well as the ripe fruit), it is by running a
program of apoptosis, and the very existence of this mechanism of v plants indicates the evolutionary antiquity of apoptosis
[15].
The pathological process that is characterized by excessive accumulation of fluid within the cells of the brain called the
swelling. OGM - an increase of the brain due to accumulation of fluid in the intercellular spaces.
Swelling of the brain is a pathological condition polietiologicheskoe at which the accumulation of extracellular and / or
intracellular fluid, which leads to an increase in brain volume and progression of its functional failure.
Depending
on
the
pathophysiological
mechanisms
are
five
types
of
brain
edema
(OGM):
A. Vasogenic - the most common form of edema. Occurs when the blood-brain barrier dysfunctions, resulting in a rise in
hydration glia. The main reasons for this type of edema are the metabolic transport systems endothelium, arterial
hypertension,
hyperthermia,
hypercapnia,
neovascularization
of
the
tumor
bed.
Two. Gidrotsefalichesky - OGM arising in the blockade of CSF outflow tracts. The main reasons are: inflammation and
bleeding in the brain ventricular system, three-dimensional intracranial processes that cause the deformation of the brain.
Three. Osmotic - OGM arising in violation of the intracellular osmotic gradient and intravascular sectors with the intact
blood-brain barrier. The main reasons are: hyperproduction of vasopressin, intravenous solutions gipoosmolyarnymi load,
inadequate
dialysis,
drowning
in
fresh
water,
hypervolemia,
polydipsia.
4. Ischemic (reperfusion) OGM due to intracellular accumulation of fluid due to gipoergoza, blockade of Na + K +-pump and
transmineralizatsii. The main reason for this type of edema is hypoxia of any origin, and postischemic reperfusion,
ammoniemia,
hypoglycemia.
Five. Cytotoxic - an intracellular OGM arising in the blockade of the mitochondrial respiratory chain. The main causes: viral
infections, carbon monoxide poisoning, cyanide, decomposition products of hemoglobin (the lysis of hematoma).
In fact, there is usually a combination of several types of brain edema. So, for example, head injury in the first hours after the
injury
prevails
Vasogenic
OGM,
which
later
joins
ischemic
and
cytotoxic.
Cerebral
edema
is
often
a
secondary
manifestation
of
underlying
disease.
It was established that involved in the pathogenesis of OGM circulatory, vascular and tissue factors. Circulatory factor can be
divided into two units. Thus, the increase in blood pressure and increased cerebral arteries leads to a significant increase in
pressure in the capillaries. There is a filtration of water from them into the intercellular space, resulting in damage to the
tissue elements. The second element is the element of damage to the tissue with a tendency to accumulate water as a result of
insufficient
blood
supply
to
the
brain.
Go to the pathogenesis of vascular factor in OGM is a violation of vascular permeability, which leads to penetration of the
protein and plasma components of blood in the tissue spaces of the brain. As a result of increased osmolarity of extracellular
fluid and there is a damage of cell membranes. Damage to cell membranes and cytoplasm of neurons - is a factor in the
pathogenesis
of
tissue
OGM.
In the current literature on the pathogenetic mechanism of OGM is divided into Vasogenic, cytotoxic, osmotic and
interstitial.
The most common Vasogenic OGM, it is the result of dysfunction of the blood-brain barrier (BBB). In its pathogenesis: Exit
the plasma into the extracellular space, increase in the volume of white matter of the brain. After swelling of the brain injury
may be formed during the first day as a reaction to the impact of mechanical energy. Develops around tumors, abscesses,
areas of inflammation, surgery, areas of ischemia. This is a perifocal edema. It can also cause self-compression of the brain.
Cytotoxic OGM mainly develops as a result of hypoxia, ischemia and intoxication. It is a consequence of the intracellular
metabolic astroglia. There is a disorder of osmoregulation membranes of brain cells, which depends on sodium-potassium
pump.Localized predominantly in the gray matter of the brain. Occurs in viral infections, toxic-hypoxic encephalopathy,
ischemic stroke, poisoning by carbon monoxide, cyanide, decomposition products of hemoglobin.
Osmotic OGM hyperosmolarity arises as a result of brain tissue without affecting the functionality of the BBB. It happens
with metabolic encephalopathy, drowning in fresh water, hypervolemia, polydipsia, inadequate hemodialysis.
Interstitial OGM develops around the lateral ventricles due to soaking water through their walls in the brain tissue.
Depending on the extent of the process of OGM is divided into local, or local, and generalized, which may cover one or two
hemispheres.
Select the most characteristic symptoms of OGM. The main one - cerebral, arising due to increased intracranial pressure. The
patient is enhanced paroxysmal headache Expander nature, against which develops vomiting, change the cardiovascular
system.There is psychomotor agitation, impaired consciousness, followed by progression of symptoms. A frequent sign -
stagnant nipples optic nerves. When OGM cerebral syndrome usually has a progressive-remittiruyusche character.
The second release syndrome, diffuse rostrokaudalnogo increase of neurological symptoms, the clinic which depends on the
gradual
involvement
in
the
pathological
process
of
brain
structures.
By the third dislocation syndrome include brain structures. As a result, the growth OGM and dislocations characteristic focal
symptoms develop. The main stem symptoms can be identified with a lesion of the oculomotor nerve. In the case of
compression of the posterior cerebral artery can appear homonymous hemianopsia. In severe dislocation of the brain develop
decerebrate rigidity, bradycardia, dysphagia, etc. There are often sudden vomiting, neck stiffness, possible respiratory arrest.
As shown by the results of many studies, one of the important links in the pathogenesis of secondary neuronal damage plays
an important role in brain edema by cerebral ischemia. Cerebral edema increases ischemia associated secondary
inflammatory reaction of the brain, promotes products hyperproduction of nitric oxide, excitatory amino acids, which
contribute to disease. This in turn requires the inclusion in the complex therapy of ischemic stroke decongestants drugs in the
early
stages
of
the
disease.
As a result of randomized, placebo-controlled and blind studies have proven the absence of a positive impact on the disease
and stroke mortality in the steroid anti-inflammatory drugs (dexamethasone) (Norris JV, 1986; Desai P., 1998; Ogun SA,
2001; Feigin JV, 2003) leading neurological clinic USA, Europe, Japan and other countries abandoned the use of
corticosteroids, before a long time and is widely used in the treatment of this pathology, in particular as anti-edema
therapy. The use of loop diuretics is limited because of the increased risk of hemodynamic disturbances as a result of blood
clots. Osmodiuretiki have rebound syndrome (in violation of autoregulation of cerebral blood flow), steal syndrome (with
critical dehydration intact areas of the brain), increasing the possibility of secondary brain damage.
In this context, the question becomes relevant selection of adequate, safe and effective anti-edema therapy for stroke. One of
these
drugs
may
be
recognized
as
L-lysine
aescinat.
The drug L-lysine aescinat ® is designed to provide medical care and prevention oteua brain in various pathologies of the
central and peripheral nervous system lesions in the brain and spinal cord, in cases of severe violations of the venous
circulation, as well as in some other cases, associated with elevated exudative and inflammatory processes.
L-Lysine aescinat and has a strong and rapid anti-edema effect, eliminates or significantly reduces swelling, swelling of the
brain and spinal cord and meninges, eliminates compression and dislocation structures of the brain, reduces intracranial
hypertension. The drug improves the elasticity of the veins, increases the tone of venous vessels, normalizes blood rheology,
stimulates the antithrombotic activity of serum, improves microcirculation, dose-dependent decrease vascular permeability
and tissue permeability barrier plazmolimfaticheskogo, reduces the activity of lysosomal enzymes and prevents the formation
of exudative reaction to prostaglandins, has a mild diuretic effect, positive effect on tissue trophism. Use of the drug also
causes immunomodulating effect, eliminated stress hyperglycemia in patients with brain damage and normal blood levels of
carbohydrates, thus preventing the development or eliminating the effects of brain tissue acidosis, and exacerbation of
cerebral injury.Pronounced immunomodulating activity of L-lysine aescinat ® prevents the risk of inflammatory
complications
or
reduce
it.
In order to study the effect of complex therapy with decongestants drugs on the clinical course of the study of secondary
hemodynamic effects of acute ischemic stroke, a comparative clinical study of Doppler sonography effective ¬ efficiency of
the drug L-lysine aescinat. The effectiveness of L-lysine is associated with membrane-aescinat effect of the drug, which in
turn is due to sosudotoniziruyuschim action and the ability to increase oncotic pressure within the capillaries, leading to the
attraction of fluid from the intercellular sector and the elimination of hypovolemia. Venotonic effect is significant in
improving venous circulation and the prevention of venous reflux. The effects of the drug due to both anti-inflammatory,
anti-edematous and effect and the end result is associated with a positive influence on the permeability and fragility of blood
vessels.The mechanism of action of the drug is associated with effects on the adrenal cortex, believe that escin stimulates the
release of glucocorticoids. In studies conducted in GNTSLS, it was confirmed that escin, as well as its hydrolysis product,
inhibits the growth of granulation tissue, ie, has an inhibiting effect on the proliferative phase of inflammation
Clinical
trials
were
conducted
on
the
basis
of
intensive
neurology
clinic
TMA-1.
Type
of
test:
an
open,
longitudinal
study
with
two
parallel
groups.
The 1st control group received conventional therapy of ischemic stroke without the inclusion of L-lysine aescinat. This group
is
made
up
of
20
patients.
Group 2 comparison (also 20 patients) received L-lysine aescinat at a dosage of 10.0 ml of twice-daily intravenous infusion
and
traditional
treatment
of
ischemic
stroke.Duration
of
treatment
10
days.
The
selection
of
patients
for
the
study:
Criteria
for
inclusion
in
the
trial:
A. patients
with
ischemic
stroke
of
moderate
and
severe
degrees
of
severity.
Two. patients
not
receiving
other
decongestants
drugs.
Three. patients without active peptic ulcer disease and gastrointestinal disorders, without the liver and kidney, with no
tendency
to
bleeding.
4. patients
without
a
history
of
allergic
burdened.
The
criteria
are
not
included
in
the
test:
A. patients
with
ischemic
stroke
is
very
severe
degrees
of
severity.
Two. Patients
receiving
other
decongestant
medicines.
Three. patients with active gastrointestinal ulcer, a violation of the excretory function of kidneys, liver failure and prone to
bleeding.
4. Patients
with
a
history
of
allergoanamnezom.
Mapping
scheme
of
the
drug:
L-Lysine aescinat administered as an intravenous injection of 10.0 ml of 0.1% solution twice a day.
In patients receiving L-lysine aescinat not use other decongestant medicines. To objectify the study included patients with
approximately the same degree of severity of disease. Serious side effects of L-lysine aescinat in patients with ischemic
stroke requiring discontinuation of the drug were observed. Assessed the severity and extent of neurological deficit
Scandinavian scale and the scale of NIHSS, Computer-tomography study and research arterialnotgo and venous components
of
cerebral
hemodynamics
by
transcranial
Doppler
data
(Logidop-4,
Germany).
Age of patients ranged from 34 to 68 years. The median age was 62,2  1,1 years. All patients received IM at the clinic in the
most
acute
period
of
disease.
We studied patients with hemispheric ischemic stroke clinical lesion was characterized by a predominance of carotid focal
symptoms: central paresis of nerves VII and XII, the presence of mono-, - hemiparesis or hemiplegia, the emergence of
pathological reflexes, and reflexes of oral automatism, combined with sensory disturbances in the form of surface or
total mono-and hemianesthesia. Defeat of the dominant hemisphere was accompanied by aphasic, Gnostic, praksicheskimi
disorders. Cerebral symptoms were observed in patients with severe stroke: impaired consciousness, and the dislocation
secondary
stem
syndrome.
For the objectification of patients with hemispheric ischemic stroke assessed their neurological status by means of two
complementary scales - Scandinavian and NIHSS (American Stroke Scale), which showed that NIHSS score mean clinical
score was 19,3 ± 1,4 balls, and on Scandinavian scale - 30,0 ± 2,2 points, in both cases indicates moderate disease course.
Assessment of the severity and extent of neurological deficit in the patients examined ischemic stroke c clinical scales
showed that on the third day of the disease indicated a significant improvement in patients (a positive shift of the NIHSS
score of 30.8%, and the Scandinavian scale at 22.4% .) Patients who were not taking L-Lysine aescinat, by the third day of
the
disease
has
a
positive
trend
statistically
significant
(Table
26).
Comparative analysis showed that on the tenth day of illness a positive trend to a decrease in neurological deficit was
significantly higher in patients treated with L-lysine aescinat (Table 1).. So, by that time the disease clinical score on a scale
of NSAIDs on the NIHSS decreased 29.51%, and the Scandinavian scale increased by 24% (p <0,05) compared with patients
treated with no L-lysine aescinat.
Table 1. Evaluation of neurological status in the course of the disease in patients with ischemic stroke in clinical scales.
Patients
with
intracerebral
hemorrhage
Prior
to
treatment
(N
=
20)
Without
treatment,
L-lysine
aescinat
(N
=
20)
treatment
with
L-lysine
aescinat
(n
=
20)
3-day
(N
=
20)
10-day
(N
=
20)
3-day
(N
=
20)
10-day
(N
=
20)
Scale
NIHSS,
score
19,3
±
1,4
17,5
±
1,6
p1>
0,05
14,7
±
1,5
p1
<0.05
12,1
±
1,2
p1
<0.001
p2
<0.05
10,4
p1
p2
±
Ckandinavskaya
31,6
p1>
p1
38,7
p1
p2
scale
0,05
score
30,0
±
37,5
±
±
±
46,5
p1
p2
Note:
1,3
<0.001
<0.05
±
p1
p2
-
reliability
relative
to
the
reliability
with
2,2
2,4
2,9
<0.05
2,5
<0.01
<0.05
3,1
<0.001
<0.05
the
respect
patient
prior
to
patients
to
without
treatment;
treatment
L-Lysine
aescinat.
The clinical observations have shown that in patients not treated with L-lysine aescinat even in the case of positive
neurological dynamics and reduce gipodensnoy zone according to the CT scan, there is the safety zone, or an increase of
perifocal
edema.
The study of cerebral hemodynamics was performed assessing the effects of the drug L-lysine aescinat on the arterial (MCA,
ACA, PCA, and OA) and venous components (IJV). Analysis of the results (Table 2) showed that the hemispheric stroke
significantly prevalent signs of asymmetry of blood flow with hypoperfusion in the affected pool (p <0,05). Local changes in
blood flow velocity with signs of turbulence, as well as a moderate increase in BFV of ACA, significantly increasing in the
contralateral CCA compression, and a significant increase in BFV of PCA in the homolateral CCA compression with a
decrease in response to MCA in response to a compression test, was observed in 45.71%. In 26.15% of cases of stroke on a
background of hypertension reported a moderate increase with the increase of BFV index of peripheral resistance and
vascular tone (Table 2). In 32% of this group is a source of collateral circulation pool contralateral common carotid artery. In
these patients, blood flow velocity in the supratrochlear artery with compression of the common carotid artery of the same
name has not changed, indicating that filling of the distal internal carotid artery blood flow from another source and confirm
the
presence
of
collateral
circulation
to
the
intracranial
level.
In a minority of patients (5%) were the source of artery blood flow vertebro-basilar basin.The value of antegrade blood flow
direction in the supratrochlear artery did not change with sequential compression of both common carotid arteries.
Table
2. Dopplerographic
intracranial
hemodynamic
parameters
examined
Surveyed
groups
Artery
Parameters
GS,
cm
/
s
PI
RI
The
control
group
(n
=
30),
left
MCA
86,4
±
8,2
0,85
±
0,12
0,55
±
0,11
Right
84,2
±
8,4
0,82
±
0,11
0,53
±
0,11
Left
ACA
73,6
±
4,3
0,84
±
0,13
0,53
±
0,15
Right
72,6
±
4,2
0,87
±
0,13
0,52
±
0,15
ZMA
left
63,2
±
7,5
0,84
±
0,12
0,55
±
0,16
Right
60,4
±
7,8
0,80
±
0,14
0,52
±
0,18
The
OA
56,8
±
4,6
0,80
±
0,12
0,49
±
0,15
Treatment with L-lysine aescinat before treatment (numerator) and after treatment (the denominator), the left MCA 63,4 ±
6,4
*
85,5
±
5,5
1,19
±
0,12
*
1,02
±
0,14
0,96
±
0,15
*
0,72
±
0,08
Right
60,9
±
6,2
*
83,3
±
5,3
1,14
±
0,13
*
0,88
±
0,06
0,95
±
0,18
*
0,76
±
0,06
Left
ACA
58,4
±
6,5
*
72,6
±
5,2
1,27
±
0,15
*
0,85
±
0,08
0,94
±
0,13
*
0,71
±
0,05
Right
57,3
±
6,3
74,2
±
6,3
1,26
±
0,14
*
1,04
±
0,13
0,92
±
0,13
*
0,73
±
0,09
ZMA
left
48,8
±
4,5
55,4
±
6,8
1,22
±
0,13
*
1,01
±
0,15
0,97
±
0,12
*
0,85
±
0,12
Right
49,6
±
4,7
56,9
±
7,1
1,20
±
0,12
*
1,02
±
0,14
0,96
±
0,12
*
0,87
±
0,13
The
OA
41,8
±
3,5
*
46,8
±
4,8
1,17
±
0,14
*
1,07
±
0,12
0,90
±
0,13
*
0,82
±
0,13
Without
treatment,
L-lysine
aescinat
(N = 30) before treatment (numerator) and after treatment (the denominator), the left MCA 62,5 ± 5,2 *
71,5
±
4,31
1,17
±
0,13
*
1,12
±
0,13
0,99
±
0,14
*
0,95
±
0,071
Right
61,6
±
5,4
*
69,3
±
4,41
1,15
±
0,12
*
1,13
±
0,101
0,94
±
0,15
*
0,92
±
0,051
Left
ACA
57,3
±
6,3
*
58,4
±
4,71
1,25
±
0,14
*
1,12
±
0,111
0,92
±
0,14
*
0,87
±
0,051
Right
59,2
±
6,2
64,6
±
6,3
1,24
±
0,15
*
1,14
±
0,12
0,93
±
0,15
*
0,81
±
0,13
ZMA
left
45,7
±
4,3
50,1
±
5,4
1,23
±
0,12
*
1,00
±
0,17
0,94
±
0,13
*
0,88
±
0,15
Right
47,2
±
4,5
52,3
±
5,1
1,21
±
0,13
*
1,01
±
0,16
0,95
±
0,14
*
0,89
±
0,13
The
OA
40,3
±
3,7
*
36,7
±
4,5
1,16
±
0,13
*
1,09
±
0,14
0,91
±
0,12
*
0,87
±
0,14
Note:
there
were
significant
indicators
relative
to
the
norm:
* - (P <0.05); ** - (P <0.01), the reliability indices with respect to the treatment with L-lysine aescinat: 1 - (P <0.05), 2 - (P
<0.01 .)
The study of the venous component of cerebral blood flow shows signs of difficulty of venous outflow from the cranial
cavity, associated with general haemodynamic changes on the background of stroke. The patients showed signs of decline
and the average linear velocity of blood flow (more than 26%) with a decrease in peripheral indices (p <0.001), impaired
phase character of the curve, indicating that overflow with obstruction of venous outflow of blood (Table 3).
Table
3. IJV
blood
flow
to
the
examinees.
Parameters control group (n = 30) treatment with L-lysine aescinat (n = 20) before treatment without treatment with L-lysine
aescinat
(N
=
20)
GS,
cm
/
s
right
27,8
±
1,05
20,5
±
1,02
***
28,3
±
1,05
21,5
±
1,03
***
24,2
±
1,042
left
to
25,3
±
1,01
22,6
±
0,98
***
27,5
±
1,08
22,4
±
0,99
***
24,3
±
1,061
PI
right
0,75
±
0,04
0,55
±
0,03
***
0,72
±
0,01
0,57
±
0,02
***
0,67
±
0,021
left
to
0,76
±
0,02
0,52
±
0,04
***
0,75
±
0,02
0,56
±
0,03
***
0,67
±
0,031
RI
right
0,47
±
0,03
0,35
±
0,02
***
0,51
±
0,01
0,33
±
0,02
***
0,45
±
0,022
left
to
0,45
±
0,02
0,33
±
0,01
***
0,53
±
0,01
0,35
±
0,01
***
0,40
±
0,031
Note:
there
were
significant
indicators
relative
to
the
norm:
* - (P <0.05); ** - (P <0.01) *** - (P <0.001), the reliability indices with respect to the treatment with L-lysine aescinat: 1 (P
<0.05 )
2
(P
<0.01),
3
(P
<0.001)
Dynamic study of cerebral hemodynamics showed that inclusion in the treatment of ischemic stroke L-lysine aescinat is a
statistically significant improvement in arterial and venous components of cerebral blood flow. Thus, in patients treated with
L-lysine significantly increased aescinat linear velocity of blood flow with a decrease in vascular tone and peripheral
resistance (Table 2), indicating an improvement of arterial perfusion in the brain tissue. Along with the improvement in blood
components of cerebral hemodynamics, and improved venous outflow, which was reflected in a significant increase in the
linear and the mean blood flow velocity with an increase in venous tone - indices PI and RI (Table 3), which is associated
with
the
drug
venotonic
properties
of
L-lysine
aescinat.
Thus, this study showed that the use of anti-edema of the drug L-lysine aescinat effectively reduces the swelling of the brain
which plays an important role in the processes of early and late neuronal lesions during the acute ischemic stroke. The use of
L-lysine aescinat accompanied by significant improvement of the clinical course of disease, a rapid decrease in the zone of
perifocal edema, as evidenced by a decrease in neurological deficit according to the clinical scales and CT studies. The use of
L-lysine improves the effective aescinat intracerebral blood flow by improving venous return, which in turn improves arterial
perfusion of the brain.
Prevention
of
recurrent
ischemic
Due to the large variety of causes underlying the stroke, it is necessary in the first days of the disease, along with these
treatments
take
measures
to
prevent
recurrence
of
stroke.
In cardioembolic stroke due to atrial fibrillation, cardiac therapy, besides the recommended appointment of indirect
anticoagulants. If there are contraindications to their use, the use of aspirin. It is believed that in order to reduce the risk of
cerebral hemorrhage, initial treatment should begin with aspirin and held until such time as will permit the main deficits
caused by stroke, or if it is a heavy stroke, after about two weeks after it began.
In arterio-arterial embolism, occlusive disease of major arteries of the head is effective use of aspirin, ticlopidine,
dipyridamole.
Treatment and prevention of secondary and recurrent haemorrhage in the brain is primarily based on a carefully selected
anti-hypertensive therapy, and prevention of recurrent ischemic stroke - on the monitoring of ECG and blood pressure.
In some cases, for the prevention of ischemic strokes are choosing surgical methods, especially when stenosis or occlusion of
the gross of the carotid and vertebral arteries embologenic, heterogeneous atherosclerotic plaques (endarterioektomiya,
revascularization.
Conclusion
Given the high incidence of CVD in the population, should give priority to solving this problem using the scientific expertise
of
physicians
around
the
world.
Undoubtedly, such an approach to the problem will yield positive results. Knowing the major risk factors for stroke, which
not only contribute to the development of the disease, but also influence its course and prognosis must be carefully approach
the
choice
of
drugs
to
treat
such
patients.
Based on the results of numerous studies on the use of the drug L-lysine aescinat, as well as your own accumulated material
for clinical testing of their effectiveness, we can recommend the drug as safe and effective for the treatment of cerebral
edema
in
ischemic
stroke.
APPENDIX. Classification
of
stroke
according
to
ICD
X
G45
Transient
cerebral
transient
ischemic
attacks
(attacks)
and
related
syndromes
G45.0
The
syndrome
of
vertebrobasilar
arterial
system
G45.1
carotid
artery
syndrome
(hemispheric)
G45.2
Multiple
and
bilateral
symptoms
of
cerebral
arteries
G45.3
Transient
blindness
Transient
global
amnesia
G45.4
G45.8
Other
transient
cerebral
ischemic
attacks
and
related
syndromes
G45.9
Transient
cerebral
ischemic
attack,
unspecified
G46
*
Vascular
syndromes
of
brain
in
cerebrovascular
diseases
(I60
I67
+)
G46.0
*
middle
cerebral
artery
syndrome
(I66.0
+)
G46.1
*
anterior
cerebral
artery
syndrome
(I66.1
+)
G46.2
*
posterior
cerebral
artery
syndrome
(I66.2
+)
G46.3
The
syndrome
of
stroke
in
the
brain
stem
(I60
I67
+)
Syndrome:
Benedict
Claude
Fovillya
Miyyara
Zhyuble
Wallenberg
Weber
G46.4
*
cerebellar
stroke
syndrome
(I60
I67
+)
G46.5
*
Pure
motor
lacunar
syndrome
(I60
I67
+)
G46.6
*
Pure
sensitive
lacunar
syndrome
(I60
I67
+)
G46.7
*
Other
lacunar
syndromes
(I60
I67
+)
G46.8
*
Other
vascular
syndromes
of
brain
in
cerebrovascular
diseases
(I60
I67
+)
Cerebrovascular
disease
(I60-I69)
I60
Subarachnoid
hemorrhage
I60.0
Subarachnoid
hemorrhage
from
carotid
sinus
and
bifurcation
internal
carotid
artery
I60.1
Subarachnoid
haemorrhage
from
middle
cerebral
artery
I60.2
subarachnoid
hemorrhage
from
anterior
communicating
artery
I60.3
Subarachnoid
haemorrhage
from
posterior
communicating
artery
I60.4
Subarachnoid
hemorrhage
from
basilar
artery
I60.5
Subarachnoid
hemorrhage
from
vertebral
artery
I60.6 Subarachnoid hemorrhage from other intracranial arteries
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