BrainMind.com
Neuroscience

Stroke and Cerebral Vascular Disease

Thrombi, Emboli, Transient Ischemic Attacks,

Hemorrhage, Aneurysms, Atherosclerosis...



R. Gabriel Joseph, Ph.D.

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STROKE & BRAIN DAMAGE DUE TO CEREBRAL-VASCULAR DISEASE

Blood Supply to the brain





STROKE

Stroke is the third most common cause of death (after heart disease and cancer) in the U.S. and Europe. Thrombosis and embolism (blood clots) account for approximately 75% of all strokes, whereas about 20% are due to hemorrhage. Up to 70% of all major stroke victims are usually permanently and significantly disabled. Of those who survive, the five year accumulative risk of repeated stroke is about 40% in men and 25% in women.


STROKE: CEREBRAL INFARCTION

When the brain is not adequately perfused with blood and is deprived of oxygen and nutrients, nerve cells begin to die and a variety of neurological, neuropsychiatric, and neuropsychological abnormalities may result depending on how long and which portions of the cerebrum are involved. As is well known, the complete deprivation of blood for longer than 3 minutes produces neuronal, glial and vascular necrosis and irreversible brain damage; i.e. cerebral infarction (stroke) and ischemic necrosis. If blood flow is reduced for a shorter time period transient neurological abnormalities may occur.

For example, at rest the human brain consumes about 20% of the total oxygen consumed by the body and 70% of the total glucose. However, unlike other organs, the brain is without oxygen or glucose storage capacity and is therefore completely dependent on the blood supply. Thus disruption of the blood supply and/or a loss of oxygen and glucose for a little as 10-30 seconds can induce dizziness, confusion, and loss of consciousness. Similarly, if cerebral blood flow drops below 40% of what is normal, electrocortigraphic silence is produced, followed by anoxic depolorization, depletion of cellular energy metabolites coupled with massive increases in extracellular potassium ions, which is followed by neuronal death (Ginsberg 2015).



Thus a cerebral infarct and the neurological symptoms which accompany it may develop quite abruptly and in a manner of seconds. However, the full symptomatic development of an infarct can be more prolonged taking perhaps minutes, hours or days; i.e. stroke in evolution.

Specifically, cerebral infarction is characterized by lack of oxygen, nutrients, and/or the impaired removal of metabolic products --conditions which result in the death of neurons, glia and the vasculature. Moreover, when cells die their membranes burst releasing lipids, fatty acids, and other substances which can produce systemic and local effects which magnify damage in surrounding zones. In addition, although the brain requires glucose in order to function effectively, increases in blood glucose levels following or during acute ischemic stroke can markedly worsen the outcome in nonlacunar strokes and can increase the risk of hemorrhagic infarction (Bruno, et., al., 1999). Hyperglycemia augments the degree and severity of ischemic injury.

Cerebral infarction or stroke is often secondary to cerebrovascular disease and vascular abnormalities involving the heart and/or blood vessels. This includes atherosclerosis, occlusion of the cerebral arteries by thrombus or embolus, or rupture of a vessel which causes hemorrhage.


Other major risk factors for stroke include hypertension, diabetes mellitus, atrial fibrillation, transient ischemic attacks, left ventricular hypertrophy, congestive heart failure, and coronary heart disease (Alter et al. 1994; Bornstein & Kelly 1991; Kimura, et al., 1999; Toole, 1990; Wolf et al. 1983). Diseases or damage involving the heart, including myocardial infarction, are leading contributors to stroke.

In addition, there are seasonal factors which contribute to stroke, due in large part to reductions in temperature (Lanska & Hoffmann, 1999). Specifically, patients are more likely to suffer a stroke and to suffer stroke-related mortality in the colder winter months. Mortality secondary to a winter-time stroke is also directly related to the increased risk for respiratory disease during the colder months of the year.


FUNCTIONAL ANATOMY OF THE HEART & ARTERIAL DISTRIBUTION

The heart is a four-chambered muscular organ about the size of a man's fist which lies predominantly to the left of the body's midline. The upper two chambers are referred to as the atria (or auricles) and the lower chambers are the ventricles. In general, blood flows from the atria to the ventricles (when the atria valves contract) and from the right and left ventricles respectively into the pulmonary artery and aorta (when the ventricular valves contract).

Oxygenation

From the pulmonary artery blood is shunted to the lungs where carbon dioxide is removed and oxygen replaced. This oxygenated blood is then transmitted to the left atrium via the pulmonary veins. From the left atrium blood is transported to the left ventricle which pumps the oxygenated blood through the aorta.

Arterial Cerebral Pathways

It is via the aorta that blood is transmitted directly to the brain. Hence, clots or other debris cast off from the heart commonly effect cerebral integrity. Specifically, the aorta gives rise to the left common carotid and brachiocephalic artery. The brachiocephalic artery bifurcates into the right common carotid and right subclavian arteries. Each common carotid divides into the external and internal carotid arteries. The subclavian arteries give rise to the vertebral arteries.

Hence, the brain is actually nourished by two separate systems of vasculature, the carotid and the vertebral. The carotid system supplies the frontal and parietal lobe, all but the inferior-posterior third of the temporal lobe, the hypothalmus, basal ganglia, and the eyes. The vertebral system nourishes the posterior temporal lobe, the occipital lobe, the upper part of the spinal cord, brainstem, midbrain, thalamus, cerebellum, and inner ear. Hence, abnormalities involving either of these circulatory systems can result in widespread, albeit characteristic disturbances.

THE BLOOD SUPPLY OF THE BRAIN

THE CAROTID SYSTEM

The internal carotid artery gives rise to four major arterial branches; the middle cerebral, anterior cerebral, opthalamic, and anterior choroidal arteries.

MIDDLE CEREBRAL ARTERY

The middle cerebral artery is a direct extension of the internal caratoid and receives almost 80% of the blood passing through this arterial system. Being a major recipient of the carotid blood supply it is often the most commonly effected part of the vasculature when debris are cast off from the heart and vessel walls.

This artery through its branches supplies the lateral part of the cerebral hemispheres, including the neocortex and white matter of the lateral/inferior convexity of the frontal lobes, the motor areas, primary and association somesthetic areas, the inferior parietal lobule, and the superior portion of temporal lobe and insula. Its penetrating branches supply the putamen, portions of the caudate and globus pallidus, posterior limb of the internal capsule and corona radiata.


ANTERIOR CEREBRAL ARTERY

Through its branches the anterior cerebral artery supplies the orbital frontal lobes, all but the most posterior portion of the medial walls of the cerebral hemispheres, and the anterior 4/5s of the corpus callosum. In this regard it might better be referred to as the anterior medial-orbital artery.


OPTHALAMIC ARTERY

The opthalamic artery is the first large branch given off by the internal carotid. The opthalamic supplies and nourishes the eye and the orbit as well as some skin on the forehead. The opthalamic also gives off branches which feed the posterior limb of the internal capsule, the thalamus, wall of the 3rd ventricle, and portions of the optic chiasm.

ANTERIOR CHOROIDAL

The anterior choroidal artery arises from the lateral side of the internal carotid and supplies the medial portion of the globus pallidus and Ammons horn, and parts of the internal capsule.

In general, the terminal arterial branches of the anterior, middle and posterior cerebral arteries (which is part of the vetebral system) inteconnect with one another over the surface of the brain such that there is some overlap in distribution.

VERTEBRAL SYSTEM

The vertebral system, via it's branches supplies the brain stem, cerebellum, and the occipital and inferior temporal lobe. Specifically, the vertebrals unite to form the basilar arteries, and the basilar gives rise to the cerebellar and posterior cerebral arteries (Carpenter 1991; Parent 2015).

VERTEBRAL ARTERIES

Each vertebral artery arises from the right and left subclavian and ascends to the medulla where they unite to form the basilar artery at the caudal base of the pons. The vertebral arteries are the chief arteries of the medulla, and supplies the lower 3/4 of the pyramids, the medial lemniscus, restiform body and posterior-inferior cerebellum.

BASILAR ARTERY

The basilar artery supplies the pons and gives rise to the inferior and superior cerebellar arteries which nourish the cerebellum. As the basilar artery ascends it bifurcates into the two posterior cerebral arteries.

POSTERIOR CEREBRAL ARTERY

The major trunks of the posterior cerebral artery irrigate the hippocampus, medial portion of the temporal lobes, occipital lobes including areas 17, 18, 19, and the splenium of the corpus callosum. Via it's deep penetrating branches it also feeds the thalamus, subthalamic nuclei, substantia nigra, midbrian, pineal body, and posterior hippocampus.

CEREBRAL-VASCULAR DISEASE OF THE ARTERIES


By definition, an artery (with the exception of the pulmonary artery) is a vessel which carries oxygenated blood away from the heart to other parts of the body. Small arteries are referred to as arterioles. Capillaries are microscopic vessels which transport blood from the arterioles to venules. Venules carry blood to veins. In general, the capillary density is greater in the gray than white matter, and the gray receives about five times as much blood and 7 times as much oxygen as the white matter.



Arteries consist of an outer coat of tough fibrous tissue, an inner lining of endothelium, and a smooth inner coat of muscle which acts to constrict and dilate the vessel. Any alteration in the smoothness of this muscular coat can give rise to the development of blood clots and thrombi. Most rough spots are secondary to atherosclerosis. Atherosclerosis is a major risk factor for stroke, and the longer the duration of initial symptoms, such as in the case of transient ischemic attacks, the more likely is it that arterial disease is a facto.

ATHEROSCLEROSIS

Atherosclerosis is a non-inflammatory degenerative disease of the arterial blood supply to the brain and the body. Atherosclerosis includes a wide range of arterial abnormalities, such as roughening of the blood vessel intima, elongation and stiffening of the artery which may cause it to kink and buckle (which in turn reduces blood flow and pressure), reductions in the caliber or dissection or tearing of the lumen (the inner arterial walls), obstruction or occlusion of the lumen with possible diversion of flow through collateral channels, focal dilations, and plaque formation coupled with occlusion and a severe reduction in blood flow, which results in ischemia and stroke.


Atherosclerosis exerts its effects indirectly on the brain by decreasing perfusion pressure and reducing flow through the tissues supplied by the various blood vessels. This is accomplished by promoting the development of thrombi and emboli (fibrin, platelets, or cholesterol crystals),which in turn increasingly occlude the arterial lumen. The metabolic demands of many areas of the brain can thus become partially deprived of oxygen and glucose.

HYPERTENSION

Hypertension is a leading cause of vascular hypertrophy, arteriosclerosis, stroke, and hemorrhage. Approximately 40% of those with arteriosclerosis are hypertensive (Toole, 1990). However, in some respects hypertension and arteriosclerosis are directly linked in that hypertension can injure the artery, which can result in aterioscolerosis, which increases blood pressure, which injures the vessel wall, which can result in clot formation (thrombi and emboli) as blood cells burst and/or collect in the area of the damaged vessels, which in turn act to obstruct blood flow passage thus increasing (at least proximal) blood pressure, which results in increased vessel damage and occlusion, and so on.

Specifically, chronic hypertension acts to reduce arterial elasticity by stretching and thickening the walls of the blood vessels including the capillaries. It can also potentiate the development of thrombi via pressure induced erosion or roughening of vessel walls. Hence, frequently the space within the vessel through which the blood flows will decrease in size. However, sometimes it is actually enlarged.

Chronic hypertension, although associated with increased blood pressure, actually can cause generalized blood flow reductions, particularly in regions served by the middle cerebral artery, i.e. the frontal-parietal and temporal lobes (Rodriguez, et al. 1987).

Hence, one consequence of hypertension is an increased risk for ischemic infarcts (Alter et al. 1994; Bornstein & Kelly 1991). That is, because the caliber of the lumen becomes fixed and rigid, the ability to dilate and thus compensate for alterations in blood pressure is lost. In consequence, if there were a decrease in blood pressure, this inability to compensate would result in a significant reduction in blood flow and thus cerebral ischemia.

If, on the other hand, blood pressure were to increase, this lack of flexibility would predispose the vessels to burst and hemorrhage. Hence, there is a strong correlation between the incidence of stroke and high blood pressure.


Hypertensive Encephalopathy

Hypertensive encephalopathy refers to an acute syndrome in which there is an absence of warning signs and a rapid development (from minutes to hours) of deficits. Patients often complain of headache, nausea, vomiting, visual disturbances, and confusion and they may develop convulsions, focal neurological signs, and/or lapse into a deepening coma or stuporous state.

Onset is often preceded by an extreme and rapid rise in blood pressure and severe hypertension. Autoregulatory responses may become abnormal such that widespread vasospasms occur accompanied by ischemia and/or the rupturing of arterioles and capillaries. The blood vessels of the brain may then begin to hemorrhage.

THROMBI

Clot Formation

Atherosclerotic development usually begins early in life, and may be due to diet, lack of exercise, and genetics. Initially, atherosclerotic disease exerting its injurious and roughening effects at the bifurcation of the various blood vessels. Endothelial cells lining the blood vessel begin to die due to the constant erosion, ulceration occurs, and blood platelets, lipids and cholesterol begin to be deposited in the arterial intima thus forming a mound of tissue.

Within a matter of seconds of blood vessel injury (regardless of cause), blood platelets will begin to adhere to the damaged areas. Indeed, blood platelets will begin to adhere to any portion of a vessel which is not perfectly smooth and contains rough spots (e.g. a patch-like accumulation of lipid or cholesterol).

When blood platelets begin to build up, they will rupture which in turn triggers the formation of thrombin and insoluable fibrin proteins, thromboplastin. These thrombin proteins act to create blood clots which further occlude the vessel.



Specifically, these fibrin proteins resemble web-like threads which are tangled together. These tangles act like nets which act to trap more blood cells and other debris which then clot together. Once started the clot tends to grow as more and more platelets are enmeshed and rupture thereby releasing more thromboplastin fibrin proteins. Furthermore, the plaques which narrow the lumen may serve as a nidus upon which even more thrombi come to adhere and from which emboli may be dislodged. Hence, these elevated fibrous plaques (thrombi) invariably grow larger and may even become vascularized. A complicated lesion is thus formed.

Obstructive Influences

As the clot grows blood flow is reduced which causes even more thromboplastin to accumulate; particularly in that these deposits create turbulence or eddy current which further damage the smooth endothelium of the artery as well as reduce resilience.

As the clot grows and thrombi increase in thickness, the lumen becomes progressively smaller which results in arterial dilation. By reducing the resilience and the diameter of the large arteries atherosclerosis can induce systolic hypertension. The driving force of the blood against vessel walls is therefore increased which causes further roughening and more plaque formation. Atherosclerosis is thus an insidious process.

When the lumen of the artery is narrowed by about 50%, pressure in the proximal segment increases whereas distal to the clot pressure begins to fall. With 70% reduction, flow is significantly decreased and neurological functioning may be altered. Typically, however, patients remain asymptomatic until there is a sudden reduction in blood flow, or thrombi or emboli are thrown off creating a complete obstruction. However, if the core of the plaque becomes necrotic and calcifies, the surface may disintegrate thus exposing the weakened underlying surface of the vessel. When this occurs the vessel may rupture and hemorrhage.

Obstruction of the artery due to atherosclerosis may produce catastrophic neurological consequences or be associated with no symptoms whatsoever. The outcome depends upon 1) the configuration of the arterial tree with which the patient was born; 2) the segment of artery involved; 3) rapidity of obstruction development; 4) the presence or absence of collateral vessels; 5) associated diseases such as hypertension; 6) triggering mechanisms, such as a sudden blow or turn of the head.

Susceptible Arteries


There is a tendency for atheromatous plaques to form at branching and curves of cerebral arteries--most frequently the internal carotid artery and carotid sinus, the vertebral arteries and their junction which froms the basilar, the main bifurcation of the middle cerebral artery, the posterior cerebral arteries as they wind around the midbrain, and in the anterior cerebrals as they curve over the corpus callosum.


Atherosclerosis seldom exists in either the coronary of cerebral artery system without the other being involved as well--it occurs in both. When the heart is involved this can lead to myocardial infarction and mural thrombi may be cast off which then flow directly to the lungs and brain. Atherosclerototic heart disease can also cause caridiac dysrhythmias or decreases in cardiac output--possibly to such a degree that cerebrovascular insufficiency results.




Risk Factors

Risk factors for cerebrovascular and carotid atherosclerosis include hypertension, increased age, diabetis mellitus, and cigarette smoking; age and hypertension being the most important. In general, the onset of atherosclerotic disease is usually in childhood and remains silent, growing slowly for 20 or 30 years before becoming symptomatic.It appears to reach its peak incidence between the ages of 50-70 and men are twice as likely as women to suffer.

CEREBRAL ISCHEMIA

When emboli, thrombi, and/or atherosclerosis reduces perfusion of brain tissue below a critical level ischemia occurs and the patient suffers a cerebral infarct. Cerebral infarction and ischemia are due to insufficiency of the oxygen and blood supply.

Ischemia leads to hypoxia and impaired delivery of glucose as well as a failure to remove metabolites and waste such as lactic acid and carbon dioxide (Qureshi, et al., 1999; Welch & Levine 1991). As infarction evolves, local edema results which may cause an increase in tissue pressure and further reduce tissue perfusion by compressing capillaries, thereby enlarging the infarction. The severity and extent of the neurological deficit is increased even further.

There is usually reduced blood flow during ischemic attacks which extends far beyond the infarct borders. This further reduce neuronal activity such that transient (as well as permanent) neurological deterioration occurs. These transient blood flow reduction are due to metabolic changes, compression of the local vasculature and temporary cessation of neural activity (due to disconnection). Initially this may make the functional effects of the stroke appear more pervasive and profound. Nevertheless blood flow is still sufficient in these border areas so as to keep this tissue alive. Hence, as the ischemia subsides and blood flow is increased to these depressed areas there occurs a considerable degree of what appears to be recovery.


The majority of infarcts are sharply delineated. Nevertheless, surrounding the area of ischemia is a concentric zone of hyperemia caused by a local loss of autoregulatory capacity and vasomotor paralysis (Ginsberg 2015). That is, there is an increase in flow to the immediately surrounding area which acts to divert blood from other areas of the brain as well as from the ischemic zone thereby increasing ischemic damage to this area. This loss of autoregulation is most evident during the acute phase of cerebral infarction. As the infarction evolves there is local edema and swelling. This causes an increase in tissue pressure and further reduced tissue perfusion by compressing capillaries. The infarction is enlarged even further.

The pathological effects of ischemia and reduced blood flow may be massive, if, for example, the internal carotid or middle cerebral artery is obstructed. Or, the effects may be minute if impaired circulation is limited to the smaller arteries and arterioles.

With moderate or massive infarction, even if quite focal, regions within the opposite hemisphere also exhibit similar but less extensive changes due perhaps to local reflexia, increased intracranial pressure, or the spillage and spread of vasoactive chemicals which effect the entire brain. That is, the other half of the brain may also suffer a stroke.

Moreover, infarction of one hemisphere may cause so much swelling that it leads to symptoms of increased intracranial pressure. When pressure increases blood flow decreases. Blood flow tends toward normal in those who recover, but remains slow throughout the affected hemisphere in those who do poorly.

Risk Factors

Risk factors for ischemic stroke include, older age, male sex, hypertension, TIAs, hypertensive heart disease, coronary heart disease, congestive heart failure, diabetes mellitus, and cold winter months.

RECOVERY & MORTALITY

Mortality rates for cerebrovascular diesase have declined in the U.S. over the course of the last 40 years (Gillum, 2011; Meier & Strauman 1991). Nevertheless, the initial death rate for individuals in the acute phase and up to 30 days after stroke is about 38%. However, 50% of those who survive this phase die over the course of the next 7 years (Dombovy et al. 2011). Moreover, mortality rates increase for those who suffer strokes during the winter months (Lanska & Hoffman, 1999).

The major determinants for short-term mortality are intraventicular hemorrhage, pulmonary edema, impaired consciousness, leg weakneness, respiratory diease and increasing age -with level of consciousness following stroke being the single most important predictor of short-term survival. The major determinants for long term mortality are low activity level, advanced age, male sex, heart disease and hypertension. However, those who suffer intraventricular hemorrhagic infarcts have a higher mortality rate than those with infarcts due to other causes (Chambers, et al. 1987; Roos et al. 2015; Schievink et al. 2015). As noted in chapter 10, those with right hemisphere damage tend to have poorer outcomes as well as higher mortality rates. In particular right parietal lobule infarcts are associated with very poor outcomes (Valdimarsson et al. 1982).

Hyperglycemia and diabetes are also associated with poor neurological recovery, and higher short-term mortality as well as increasing the risk for stroke in general. This is because diabetes and hyperglycemia both accentuate ischemic damage. Hyperglycemia also appears to have a negative effect on energy metabolism due to the generation of severe lactic acidosis (Rehncrona et al. 1980) --factors which act to retard neuronal recovery.

Some authors have argued that luxury perfusion and increased cerebral blood flow (CBF) within an infarcted cite is often indicative of a good prognosis, wheras low CBF is a bad prognosis (Olsen et al. 1981). Presumably increased flow acts to nourish damaged tissue. Other studies however, indiate that initial CBF levels are not predictive of clinical outcome (Burke et al. 2011). Apparently this is because once damage occurs during the initial period of ischemia, these cells cannot be salvaged (Heiss & Rosner, 1983).

Hence, blood flow increases only when undamaged neurons return to a functionally active state (Burke et al., 2011) rather than acting to rejuvinate injured tissue. In fact, hyperperfusion may endanger neuronal recovery. On the otherhand oxygen metabolism seems to correlates better with clinical status and functional recovery than does blood flow (Wise et al., 1983).

Recovery is often greatest during the first 30 days after stroke, but continues up to 6 months in some patients. It has been estimated that although about 60% of stroke patients are able to achieve total independence in activities of daily living (Meier & Strauman 1991; Wade & Hewer, 1987) only approximately 10 to 30% of initial survivors return to their jobs without gross or obvious disability. Depending on the nature of the stroke, about 40% demonstate mild disability, 40% are severely disabled, and 10% require institutionalization .


Thrombi, Emboli & Transient Ischemic Attacks

Cerebral infarction or stroke is often secondary to cerebrovascular disease and vascular abnormalities involving the heart and/or blood vessels which induce the formation of thrombi and emboli which in turn may occlude the blood vessels, which reduces the blood supply to the brain thereby inducing ischemia or or rupture of the vessel which causes hemorrhage.

THROMBI

The development of thrombi is generally a consequence of (as well as a contributing factor to) atherosclerosis and injury to the endothelial cells lining the blood vessel. Blood platelets, lipids and cholesterol begin to be deposited in the injured arterial intima thus forming a mound of tissue (e.g. a patch-like accumulation of lipid or cholesterol).

When blood platelets begin to build up, they will rupture which in turn triggers the formation of thrombin and insoluable fibrin proteins, thromboplastin. These thrombin proteins act to create blood clots which further occlude the vessel.


Specifically, these fibrin proteins resemble web-like threads which are tangled together. These tangles act like nets which act to trap more blood cells and other debris which then clot together. Once started the clot tends to grow as more and more platelets are enmeshed and rupture thereby releasing more thromboplastin fibrin proteins. Furthermore, the plaques which narrow the lumen may serve as a nidus upon which even more thrombi come to adhere and from which emboli may be dislodged. Hence, these elevated fibrous plaques (thrombi) invariably grow larger and may even become vascularized. A complicated lesion is thus formed.


Obstructive Influences

As the clot grows blood flow is reduced which causes even more thromboplastin to accumulate; particularly in that these deposits create turbulence or eddy current which further damage the smooth endothelium of the artery as well as reduce resilience.

As the clot grows and thrombi increase in thickness, the lumen becomes progressively smaller which results in arterial dilation. By reducing the resilience and the diameter of the large arteries atherosclerosis can induce systolic hypertension. The driving force of the blood against vessel walls is therefore increased which causes further roughening and more plaque formation. Atherosclerosis is thus an insidious process.

When the lumen of the artery is narrowed by about 50%, pressure in the proximal segment increases whereas distal to the clot pressure begins to fall. With 70% reduction, flow is significantly decreased and neurological functioning may be altered. Typically, however, patients remain asymptomatic until there is a sudden reduction in blood flow, or thrombi or emboli are thrown off creating a complete obstruction. However, if the core of the plaque becomes necrotic and calcifies, the surface may disintegrate thus exposing the weakened underlying surface of the vessel. When this occurs the vessel may rupture and hemorrhage.


THROMBOSIS

When a thrombotic clot enlarges sufficiently the patient suffers a cerebral infarct; i.e. thrombosis. A thrombosis is due to a thrombus--a clot produced by coagulated blood (thromboplastic: a protein that forms clots). Thrombotic strokes often occur during periods of prolonged inactivity or sleep such that the symptoms are present upon arising in the morning. As the patient attempts to swing out of bed or a chair, they find that they are weak on one side, that they cannot speak, or that some other deficit has developed.

Thrombotic strokes developed gradually. Symptoms and signs usually progress in a stepwise fashion, sometimes taking 2-4 days to fully develop. Patients deteriorate, improve slightly, then deteriorate further; a process referred to as stroke in evolution. This stepwise evolution is due to edema and alterations in blood flow and metabolism as thrombotic particles continually form and break off. Stabilization with improvement begins after 7-14 days after stroke onset.

The size of the infarct in part is dependent on the presence and integrity of collateral vessels. If collateral circulatory channels are not in existence, occlusion exerts drastic effects and the infarct is quite large.

Warning signs include headache and/or previous transient neurological symptoms or a transient ischemic attacks (TIA). When transient ischemic attacks precede a stroke, they almost always stamp the process as thrombotic. However, the long the duration of the TIA, the grater is the likelihood that the infarct is due to embolism (Kimura et al., 1999).

The most common cause of thrombotic stroke is arteriosclerosis. Thrombosis follows clotting of the blood at a site where its flow is impeded by a sclerotic plaque usually in the bifurcations of the carotids. Complete occlusion of the carotids is always the consequence of thrombosis.

EMBOLISM

In contrast to a thrombosis which is due to a localized buildup, emboli are free particles which become lodged within a vessel causing occlusion. Like throbosis embolic strokes create an ischemic cerebral infarct. However, unlike thrombosis, embolitic strokes are often followed later by hemorrhage (Chamorro et al. 2015). Both thrombotic and cerebral embolic strokes occur most commonly among older individuals. Among younger age groups, however, embolism is the most frequent culprit.

An embolism may be composed of thrombotic particles which have broken off from a clot, air bubbles, masses of bacteria, or blood clots. They may also consist of cholesterol crystals which are thrown off from atheromatous plaques situated in the vertebral-basilar and carotid arteries, pieces of tumor cells from the lung, stomach, or kidney which subsequently take root in the brain after drifting in the bloodstream, and fat globules released into the bloodstream after trauma to the marrow of the long bones (Toole 1990). Oral contraceptives among women can give rise to the development of embolism, and an association among those with mitral valve prolapse has been noted.

LACUNAR STROKES

The term lacune is associated with the development of small holes in the subcortical tissue and it is often secondary to the occulsion of a deep single perforating artery (Cummings & Mahler 1991; Fisher, 1969). The most common type is due to an occlusion via macrophage plaques. Approximately 20% of all infarcts are lacunar (Bamford et al.1987; Kunitz et al. 1984). However, the incidence increases with age.

In lacunar strokes, there is usually no impairment of consciousness or higher cognitive functioning. However, if the lesion involves the internal capsule there may be motor disturbances including paralysis, or facial or arm weakness. If involving the thalamus sensory sensation over various body parts may be attenuated. The incidence of fatality is very low. Nevertheless, over a third of affected patients may be seriously impaired as long as 1 year post stroke (Bamford et al., 1987; Meier & Strauman 1991). Usually, since the stroke is so tiny, CT scan is negative.

MULTI-INFARCT DEMENTIA

In some instances individuals will repeatedly suffer small strokes over a number of years. At first these strokes seem asymptomatic or have only mild consequences. However, with repeated incidences patients (or family members) may notice their memory is not as good as before, that they are having difficulty concentrating, are sometimes confused, have increased word finding difficulty as well as other linguistic problems (Cummings & Mahler 1991). Personality and emotional changes may be subtle at first as well.

Essentially, as the lesion expands, due to repeated, albeit small strokes, the patient gradually deteriorates, until finally what was a series of minor deficits is suddenly a major alteration in personality functioning and intellectual capability. Frequently these individuals and family members erroneously describe the onset as sudden as they tended to ignore the stepwise progression of increasingly severity. However, careful questioning will reveal that the patients symptoms had been progressing over time.

In addition, patients with multi-infarct dementia have been reported to have bilateral patchily reduced blood flow in the gray matter, particularyy within the distribution of the middle cerebral artery (Cummings & Mahler 1991; Yamaguchi et al. 1980). The reductions are related to the degree of dementia severity (Kitagawa et al, 1984; Meyer et al. 2012). In general the pattern of reduction is suggestive of widespread and diffuse cerebral ischemia or infarction, and the regions involved include the thalamus, and frontal and temporal lobes. Nevertheless, patients with multi infarct dementia are frequently diagnoses as suffering from Alzheimers disease (see Blumenthal & Premachandra 1992).

HEART DISEASE, MYOCARDIAL INFARCTION & CARDIAC SURGERY

ISCHEMIA & HEART DISEASE

The delivery of oxygen to the brain depends on the vascular, pulmonary and cardiac system, the flow characteristics of the blood, and the quality and quantity of the hemoglobin molecules and the binding of oxygen to those molecules (Grotta et al. 2011). Abnormalities involving red blood cell structure or concentration are frequent causes of cerebrovascular abnormalities (Grotta et al., 2011) and can create conditions which promote coronary heart disease, abnormal clotting and thus reduced blood flow.

Coronary heart disease (even when asymptomatic) is a major underlying contributor to the development of regional decreases in cerebral blood flow, cerebral infarction and ischemia (Di Pasquale et al., 2011). In many cases patients suffer cerebral deterioration even in the absence of stroke. It is not uncommon for patients to note that their memory or other cognitive disturbances began soon following a heart attack or major surgery.

However, in some cases, an otherwise normal heart may be injured secondary to pulmonary edema following hemorrhage. This in turn may lead to vasospasm and thus an addition cerebral infarction (Mayer et al. 1994b).

MYOCARDIAL INFARCTION

When an individual has a myocardial infarct blood pressure, cerebral blood flow and metabolism fall by as much as 50% (Toole, 1990). Cerebral-vascular insufficiency and cerebral infarction are thus a likely consequence. With cardiac arrest blood pressure and flow ceases and widespread cerebral ischemic damage results (Welch & Levin 1991).

Myocardial infarction is a major contributor to stroke. When myocardial infarction occurs, thrombi are cast off from the heart and supporting vessels into the blood and carried to the cerebral vasculature causing occlusion. In fact, following a heart attack embolic events may continue for up to a month, the patient suffering a series of small or major cerebral infarctions. This is because during the healing process mural thrombi and embolisms clots may continually form and break off. If major occlusions occur within the vertebral system the patient may die. Indeed, myocardial infarction is the leading cause of mortality among patients with stroke.

GLOBAL ISCHEMIA


Global ischemia is due to a sudden and complete reduction in arterial pressure such as occurs during myocaridal infarction. If it persists for more than a few minutes widespread damage in the cortex, hippocampus, basal ganglia, brainstem, and cerebellum results. Also areas at the junctions between the various vascular territories, i.e. watershed areas, are especially vulnerable.

VALVULAR INSUFFIENCY

During a heart cycle, the atria and ventricles contract and relax successively; this is the hearts beat. However, if any of these valves lose their ability to close, blood will leak backwards, a condition referred to as valvular insufficiency. If the left atria-ventricular passageway were to become narrowed (mitral stensosis), blood flow is hindered and circulatory failure results accompanied by massive cerebral ischemia and neuronal death. The death rate among stroke patients with coronary artery disease has been estimated to be over 50% (Di Pasquale et al. 2011).

FIBRILLATION

Atrial fibrillation and tachy-bradycarida are abnormalites of rhythm and conduction which deprives the brain of adequate perfusion. Moreover, thrombi can be thrown off which in turn become a source of emboli and vascular occlusion (Barnett, 1984). The clincial pictures may include syncope or severe diffuse hypoxia.

MITRAL VALVE PROLAPSE

Mitral valve prolapse is due thickening, elongation, altered collagen compostion, as well as basic "wear and tear" of the mitral valve leaflets (Barnett, 1984; Cole et al. 1984; Jackson, 2011; Lucas & Edwards, 1982). This causes the mitral valves to baloon back (prolapse) into the left atrium during ventricular contraction. This disturbance can in turn disrupt blood flow to the brain and create ischemic conditions. However, thrombi also tend to form on the abnormal mitral valve and thus become thrown off into the blood supply ((Barnett, 1984).

The opthalamic and posterior cerebral arteries seems to be particularly effected as retinal ischemia as well as transient global amnesia seems to be a frequent consequence (Jackson, 2011; Wilson et al. 1977). However, the cerebral hemispheres are just as frequently affected (Barnett, 1984; Jackson, 2011). Nevertheless, the risk of stroke, at least among young individuals is rather low. However, mitral valve prolapse is associated with the development of infective endocarditis.

Mitral valve prolapse has also been associated with the development of chronic anxiety, agoraphobia, and panic disorders (Klein & Gorman, 1984). The causal nature of this relationship, however, is unclear. Possibly individuals who are susceptible to anxiety disorders who also suffer from mitral valve prolapse, respond to these symptoms with increased fear ands anxiety. That is, mitral valve prolapse exacerbates an already disturbed emotional condition (Jackson, 2011).

VASOSPASM

Arteries may spasm when emboli pass and/or occlude an artery, if an aneurysm ruptures, or if a vessel is manipulated or traumatized in some manner (Toole, 1990) such as after a head injury. They have also been known to occur among individuals whose arteries tend to be hyperreactive, i.e. young women (Toole, 1990). Spasm may be diffuse or segmental along the artery.

When a spasm occurs there is a transient stoppage of the flow of blood. If prolonged the patient will suffer ischemic cerebral damage. Moreover, spasm sometimes causes embolic particles to be dislodged from the vessel wall which then occludes smaller distal arteries. Cerebral infarction is therefore a likely consequence of spasm.

MURMURS

Murmurs (or bruits) are sometimes produced by changes in the direction of blood flow such as at the bifurcations of the arteries. Frequently they are a consequence of alterations in the wall of the blood vessel including shrinkage of the luminal diameter. In general, murmurs become audible after the lumen has been reduced by about 50% (Toole, 1990), and with increasing stenosis the volume and pitch become louder and higher.

Murmurs are often indicative of atherosclersosis, and are most intense over the site of the lesion. However, they may be heard over vessels other than the effected artery. Bruits are graded from 1-6, 1 being the most mild and 6 being the loudest.

CARDIAC SURGERY

A few years ago we were witness to the catastrophic effects of artifical heart surgery and implantation on various human experimental human subjects such as Dr. Barney Clark and others in the early 1980s.. All these unfortunate individuals suffered extremely serious cerebral damage due to repeated and massive strokes. Although not well publicised, the effects of heart transplantation (Hotson & Pedley, 2006; Montero & Martinez, 2011; Schober & Herman, 1973 ), and even open heart surgery can create similar disasterous consequences.

For example, a variety of studies have indicated that although motor and other initial impairments secondary to cerebrovascular disease generally improve after open heart surgery, significant deterioration in regard to personality, intellectual, visual-spatial, perceptual, memory and attentional functioning often occurs (Aberg & Kihlgren, 1974; Heller, Frank, Kornfled, et al. 1974; Gilberstadt & Sako, 1967; Lee, Miller & Rowe, 1969; Lee Brady, Rowe, 1971; Raymond et al. 1984; Shaw et al., 1987).

Open heart surgery can also cause and induce stroke (Smith et al. 2011). Frequently, the effects are diffuse rather than focal (Sotaneiemi et al. 2011).

Cardiac surgery may cause cerebral injury due to reduced blood blow and arterial pressure, macroembolization of fat, air or other gasses, the dislodgement of debri from the valves, and the initiation of blood cell and platelet aggregation (Shaw et al. 1987) In fact, just the process of opening the chest cavity via sternal retraction can reduce oxygen intake if the brachial plexus is traumatized (Baisden et al. 1984).

In general, the cerebral effects of heart surgery appear to be age dependent. Children seem to be more resilant as the long term consequences on cerebral functioning are less drastic (Whitman et al. 1973).

Given the above, and the common knowledge that the majority of certain types of heart surgery (e.g. so called "triple bypass") seem to have no proven benefit, it may be extremely wise to be cautious before undergoing these procedures. Certainly, to further clarify these risks, there is a need for a series of rigorous neuropsychological studies to be conducted on such patients both pre and post surgery. Nevertheless, sometimes CNS functioning is improved due to the correction of circulatory abnormalities and increases in blood flow (Sotaneiemi et al.2011).

HEART TRANSPLANTS

A common supposed side effect of heart transplants were changes in personality; the explanation being that patients would assume the personality of the donor. In reality, however, many of these patients experienced alterations in mental and personality functioning because they suffered strokes. Based on a review of the few studies conducted, it appears that heart transplantation carries very significant risks in regard to cerebral functional integrity. This is because many of these individuals have severe vascular disease which is not confined to the heart, such as atherosclerosis and the presence of mural and arterial thrombi. Hence, during the trauma of surgery, debri can be loosened and cast into the blood and various vessels may go into spasm creating serious complications involving the brain (Hotson & Pedley, 2006; Montero & Martinez, 2011; Schober & Herman, 1973).

Other primary and secondary consequences of heart transplanting on the brain include vascular lesions due to circulatory collapse, decreased cardiac output and chronic postoperative hypotension, thrombosis, embolism, hemorrhage as well as hypoxic damage and opportunistic infection due to depressed immune status (Montero & Martinez, 2011). In this regard, it certainly seems that frequently these individuals trade an unhealthy heart for a damaged brain. The 5-year survival rate of heart transplantation is 50% (Montero & Martinez, 2011).

It is important to note, however, that there is a paucity of neuropsychological research on the effects of heart transplantation on cerebral functional integrity. Perhaps the immediate and long term affects are not as dismal as this short review suggests.


CARDIAC EMBOLIC ORIGINS

Cerebral emboli may develop when there is plaque buildup on the cardiac or carotid valves and may also result from mitral stenosis, arterial or auricle fibrillation, aortic valve calcification, fragments of left atria or ventricular thrombus, mitral valve polips, myocardial infarction, or vegetations of infective endocarditis.


Heart disease, mitral stenosis and atrial fibrillation are thus major risk factors for cerbral embolism. Chronic atrial fibrillation in particular carries a high risk of stroke (Bornstein & Kelly 1991; Petersen & Godtfredsen, 2011; Wolf et al, 1983), the clot coming from a paralyzed atrium. When the embolus is infected, meningitis or abscess may develop. Indeed, it is estimated that approximately 90% of emboli from the heart end up in the brain. Thus embolic stroke is often a sign of systemic heart disease.

EMBOLI & THE CAROTID & LEFT MIDDLE CEREBRAL ARTERY.

In general, emboli expelled from the heart and the left ventricle are carried into the brachiocephalic artery and then the left common carotid. From the left carotid, emboli are transmitted and occlude the arteries supplying the left cerebral hemisphere. Hence, the left side of the brain is a common destination of emboli originating in the heart.

When emboli are repeatedly freed into the blood system they tend to lodge in the same artery, usually the middle cerebral. This is because the middle cerebral artery is a direct extension of the internal cartoid and receives almost 80% of the blood. Hence, most emboli end up within the middle cerebral system.

ONSET

After the lodgment of an embolus the vessel usually goes into spasm and thrombosis may occur. Embolic strokes characteristically begin suddenly, often while the patient is awake and active. There is usually no warning, and the effects of the infarction may reach its peak almost immediately (Adams & Victor 2014). However, it is not uncommon for the initial manifestations of these strokes to have a duration of 2 to 15 minutes (Kimura, et al., 1999).

Cerebral embolization will be major if the embolus is large or temporary is the fragment is small. Smaller fragments have a greater likelyhood of disintegrating. Not infrequently an extensive dificit from embolism reverses itself dramatically within a few hours or a day or two (Absher & Toole 1996; Meier & Strauman 1991). It is not uncommon for many to suffer a recurrence, frequently with severe damage (Kimura et al., 1999(. Early anticoagulant therapy should be emphasized as it is important in the prevention of embolic stroke recurrence (Chomorro et al. 2015; Lodder & van der Lugt, 1983; Koller, 1982).

EMBOLIC HEMORRHAGE

Approximately 65% of those with a cerebral embolic stroke develop hemorrhagic infarction. Conversely, less than 20% of those with thrombosis will develop hemorrhage (Ott et al. 2011). Similarly, approximately 50% of all hemorrhagic infarcts are associated with embolic strokes (Fisher & Adams, 1951; Hart & Easton, 2011). Hence embolic strokes have a special propensity for hemorrhagic transformation and hemorrhagic infarction nearly always indicates embolism.

Blood vessels effected by embolism characteristically hemorrhage within 12-48 hours. However, the hemorrhage may take several days to fully develop (Laureno et al. 1987). Hemorrhagic transformation occurs when the emboli disintegrates and/or migrates distally thus allowing reperfusion of the damaged vessel (Fisher & Adams, 1951: Jorgensen & Torvic, 1969). That is, when a vessel is occluded, it is damaged and weakened, and both the brain and the involved portion of the vessel may become necrotic. When the weakened portion of a previously occluded vessel is subsequently reexposed to the full force of arterial pressure it ruptures and hemorrhages. Fortunately, blood vessels have he capacity to regenerate.

Frequently embolic hemorrhages are asymptomatic (Hakim et al. 1983; Ott, et al., 2011) and supposedly benign since the tissue involved has already been damaged. However, if the hemmorhage is secondary to anticoagulant therapy the bleeding may be more profuse and cause significant neurological deterioration and even death.

TRANSIENT ISCHEMIC ATTACKS

Transient ischemic attacks (TIAs)are due to a brief and temporary reduction in blood flow to a focal region within the brain, though the TIA itself may last from 2 to 15 minutes (Kimura et al., 1999). Short duration TIA's are accompanied by transitory and focal neurological disturbances which seem to immediately and completely resolve with no apparent residuals. However, longer duration TIAs are indicative of serious arterial disease (Kimura et al., 1999) which increase the risk of stroke.

The most frequent cause of TIAs is atherosclerosis and microembolization of platelet aggregates from ulcerated atherosclerotic plagues within the carotids or from the caridiac valves (Adams & Victor 2014). These conditions act to reduce blood flow. Other causes include vascular spasm, aggregations of cholesterol crystals, fibrin and/or blood platelets which temporarily occlude a vessel, or a combination of these factors.

TIAS are related to the microcirculation where small irritants such as an embolus can lead to blockage. However they can involve any cerebral or cerebellar artery. TIA's may last a few seconds or up to 12-24 hours. As noted, most last 2 to 15 minutes. The symptoms are transient because the occluding emboli almost immediately disintegrates which allows for the immediate reestablishment of blood flow and functional recovery.

TIAS which last less than 60 minutes are different from those of longer duration. The shorter ones are due to emboli which travel from one artery to another, whereas the longer ones are from emboli passed by the heart.

Hence, artery to artery emboli tend to be smaller and more quickly disintegrate whereas those from the heart tend to be larger and/or greater in number. Some patients may experience a single episode of TIA in a life time whereas others may have as many as 20 attacks in a single day. Usually they are fewer than one or two a week.

Weakness or numbness of a single finger may be the only manifestation of a TIA. However, a person may suffer a TIA and not be conscious of it, or the manifestation may be a disturbance in memory, speech and word finding, brief confusion, etc. Usually with these kinds of disturbances the patients and their families ignore, fail to notice, or attribute little significance to these attacks as they are transient.

In some instances, the TIA may take the form of temporary blindness, like a shade being pulled over the eye. It is when the patient becomes aware that there is a loss of vision, or a loss of strength in the hand or foot which rapidly progresses to involve the entire extremity that they become alarmed.

TIAs can occur within any region of the cerebral vasculature. Some investigators, however, have classified them as either opthalmic, hemispheric, or vertebral-basilar.

HEMISPHERIC TIAs


In hemispheric attacks, ischemia occurs foremost in the distal territory of the middle cerebral artery, producing weakness or numbness in the opposite hand and arm--however, different combinations may occur: face and lips, hand and foot, fingers alone, etc. In ocular attacks, transient monocular blindness occurs, and is described as a shade falling smoothly over the visual field until the eye is blind. The attack clears smoothly and uniformly.

VERTEBRAL-BASILAR TIAs


If it occurs in the vertebral-basilar system, there may be dizziness, diplopia, dysarthria, bifacial numbness, and weakness or numbness involving part or parts of the body, or even both body halves (due to the involvement of diverse regions of the brainstem and thalamus supplied by the vertebral-basilar system). Other symptoms may include in order of frequency: headache, staggering, veering to one side, feeling of crosseyedness, dark or blurred or tunnel vision, partial or complete blindness, pupillary changes, and paralysis of gaze (Toole, 1990). In basilar artery disease each side of the body may be affected alternately. There is good evidence that TIAs may be abolished by anticoagulant drugs.

TIA & STROKE

Forty percent of individuals with TIAs subsequently suffer brain infarction, the majority of which occur within the first six months (Wolf et al., 1983). Stroke may occur after the first or second TIA or only after 100s have occurred over a periods of weeks or months. However, the greatest risk of stroke following TIA is within the first year and in particular the first 30 days; 20% occuring in the first month, and 50% within a year (Bornstein & Kelly 1991; Wolf et al., 1983).

When TIAs precede a stroke, however, they almost always stamp the process as thrombotic (atherosclerotic thrombosis). Nevertheless, it is noteworthy that although thrombotic strokes are said to occur predominantly at night the majority of infarctions in general occur between 6 am and 6 pm (Van Der Windt & Gijn, 2012).

Risk Factors

Risk factors include cigarette smoking, previous history of stroke or TIA, ischemic heart disease, and diabetes (Bornstein & Kelly 1991; Howard et al., 1987). As the number of risk factors increase the prognosis for recovery following stroke declines.


HEMORRHAGE

Hemorrhage can occur anywhere throughout the brain and may be due to a number of causes, e.g., head injury, hypertension, rupture of an aneurysm or arterial venous malformation (AVM), the weakening of a segment of the vasculature secondary to emboli or thrombus, or vessel wall necrosis due to occlusion and ischemia (Adams & Victor 2014; Roos et al. 2015).

Hemorrhages are frequently classified in terms of gross anatomical location. These include, extradural, subdural, subarachnoid, intercerebral/cerebral, and cerebellar. Extradural and subdural hemorrhages are frequently secondary to head injury, whereas subarachnoid, cerebral and cerebellar hemorrhages are often related to arterial abnormalities. Bleeding from a hemorrhage may be minute and inconsequential, or profuse and extensive such that a large pool of blood rapidly develops. In some cases bleeding may occur at a very slow, albeit continuous pace such that the adverse effects are not detected for days.

SUBARACHNOID HEMORRHAGE

Subarachnoid hemorrhage results from any condition which causes blood to leak into the subarachnoid space. Massive subarachnoid hemorrhage is usually due to rupture of an intracranial aneurysm, or bleeding from a cerebral angioma--in either case there is no warning and the onset is quite sudden and abrupt (Adams & Victor, 1994; Roos et al. 2015; Schievink et al. 2015). If the hemorrhage is severe it may lead to immediate coma and death, particularly if there is a buildup of over 20 ml of intraventricular blood (Roos et al. 2015). If moderate, the patient may pass into a semi-stuporous state, and/or become confused and irritable. If minor patients may complain only of severe headache and possibly develop focal deficits after hours or over the course of the first few days or weeks following hemorrhage. Vasospams and rebleeding are very common during the first two weeks.

Subarachnoid hemorrhage has a mortality of over 50% , a third of whom will die immediately or within the first 24 hours (Schievink et al. 2015). Only approximately 25% who survive will make a good recovery (Hijdra et al. 1987).

Subarachnoid hemorrhage occurs most often among individuals above age 50. When it occurs among among younger individuals it is often secondary to congenital vascular abnormaltiies, including angioma, ruptured aneurysms or via the rupture of an AVM on the brain surface (Adams & Victor, 2014; Brown et al. 1991; Schievink et al. 2015; Toole, 1990). Rupture or seepage into the ventricular system is not uncommon (Roos et al. 2015), and CSF is bloody in 90% of cases. Anemic and hemorrhagic infarction may coexist in the same lesion.

Headache and vomiting are immediate common sequela of hemorrhage (as well as cerebrovascular disease) and most patients will complain of severe backache and neck stiffness in the absence of demonstrable focal signs which develop later (Gorelick et al. 2011; Portenoy et al. 1984). Onset is sudden and the intensity is described as severe or violent. These headaches are diffusely distributed over the cranium and/or are localized to the frontal-parietal region (Gorelick et al., 2011). Headaches are usually due the pressure effects of escaping blood which distend, distort, or stretch pain-sensitive intracranial structures. Pain in or behind the eye is often associated with hemorrhage of posterior communicating-carotid aneurysms (Gorelick et al., 2011).

CEREBRAL/INTRACEREBRAL HEMORRHAGE

Cerebral hemorrhage is commonly caused by hypertension and associated rupture aneurysm and degenerative changes in the vessel wall of penetrating arteries which make them suceptible to rupture (Kase, 2011; Schievink et al. 2015). Onset is always sudden.

The rupture may be brought on by mental excitement of physical effort, or may ocur during rest or sleep. Usually the the patient complains of sudden headache and may vomit and become confused and dazed with progressive impairment of consciousness over several minutes or hours time (except in the most mildest of cases). However, it may evolve gradually taking hours or days to become fully developed, and there may be no warning signs (Mayer et al. 1994).

After a large hemorrhage the affected hemisphere becomes larger than the other due to swelling. As the pool of blood increases and begins to clot, surrounding tissues become compressed, the convolutions become flattened and pressure may be exerted against the opposite half of the brain causing damage in this region also. With large hemorrhages, coma and death may ensue due to compression of midline and vital brainstem nuclei (Adams & Victor, 1994; Mayer et al. 1994). If the patient survives and the clot is not surgically removed it is eventually absorbed and replaced by a glial scar. In these instances, however, patients are commonly incapacitated to varying degrees. Cerebral hemorrhages occur most often in the vicinity of the internal capsule, corona radiata, frontal lobe, pons, thalamus and putamen (Adams & Victor, 1994; Kase, 2011).

The neurological deficit is never transitory (good functional recovery being attained by less than 40% of the survivors) and 30 to 75% die within 30 days (Adams & Victor, 1994; Fieschi et al. 2012; Portenoy et al., 1987). Most patients suffer persistent, permanent, and severe neurological abnormalities. Good clinical outcome is related to lower age, the size of hemorrhage, the time period the patient was unconscious, high scores on the Gasgow Coma Scale, and post-operative neurological events (Meier 1991; Portenoy et al. 1987; Tidswell et al. 2015; Toole, 1990).

In over 60% of the cases, intracerebral hemorrhage is related to hypertensive cerebrovascular disease (Mohvr et al. 2008) which makes vessels susceptible to rupture. That is, hypertension can induce degenerative changes and may in fact induce the formation of microaneurysms particularly in the subcortical and perforating arteries (Kase, 2011). However, not all cerebral hemorrhages are due to hypertension.


EMBOLIC HEMORRHAGE

When emboli and other debris build up or occlude the artery, the arterial wall will begin to die and then rupture, and the vessel with hemorrhage out its contents. Approximately 65% of those with a cerebral embolic stroke develop hemorrhagic infarction. Conversely, less than 20% of those with thrombosis will develop hemorrhage (Ott et al. 2011). Similarly, approximately 50% of all hemorrhagic infarcts are associated with embolic strokes (Fisher & Adams, 1951; Hart & Easton, 2011). Hence embolic strokes have a special propensity for hemorrhagic transformation and hemorrhagic infarction nearly always indicates embolism.

Blood vessels effected by embolism characteristically hemorrhage within 12-48 hours (Cerebral Embolism Study Group, 1984; Hart & Easton, 2011). However, the hemorrhage may take several days to fully develop (Laureno et al. 1987). Hemorrhagic transformation occurs when the emboli disintegrates and/or migrates distally thus allowing reperfusion of the damaged vessel (Fisher & Adams, 1951: Jorgensen & Torvic, 1969). That is, when a vesssel is occluded, it is damaged and weakened, and both the brain and the involved portion of the vessel may become necrotic. When the weakened portion of a previously occluded vessel is subsequently reexposed to the full force of arterial pressure it ruptures and hemorrhages. Fortunately, blood vessels have he capacity to regenerate.

Frequently embolic hemorrhages are asymptomatic (Hakim et al. 1983; Ott, et al., 2011) and supposedly benign since the tissue involved has already been damaged. However, if the hemmorhage is secondary to anticoagulant therapy the bleeding may be more profuse and cause significant neurological deterioration and even death.

ANEURYSMS, AVMs, AMYLOID ANGIOPATHY, DRUGS & TUMORS

Hemorrhage may occur secondary to drug use, anti-coagulant therapy, medication, AVMs, aneurysms, vessel wall necrosis, brain tumors, and various types of arterial pathology, including small vascular malformations, and cerebral amyloid angiopathy.

ISCHEMIA & HEMORRHAGIC INFARCTS

Ischemia not only results in the death of brain cells but necrosis of the local vasculature which is also deprived of metabolic support (Welch & Levine 1991). These vessel wall ischemic structural alterations make them very susceptible to rupture. Indeed, over 40% of those with cerebral ischemic infarction will become hemorrhagic within one to two weeks (Hornig et al. 2011).

These ischemic related hemorrhagic infarcts (HI) are not limited to a single vessel, however. Bleeding may be mutlifocal, particularly if the patient had suffered a large stroke.

In part, this is also due to the more extensive edema associated with large strokes. When swelling occurs not only is brain tissue compressed but the endothelium of various small vessels is also crushed and damaged. When these vessels are compressed blood flow is prevented which in turn makes these same vessels and their distal extensions more susceptible to rupture when blood flow is reestablished (Garcia et al., 1983). That is, with blockage of a vessel, the distal part of the vessel may become necrotic. Even with mild degrees of edema there is compressions and subsequent damage to various small vessels surrounding the lesion (Welch & Levine 1991).

Hemorrhagic infarcts are not usually associated with chronic hypertension (Hart & Easton, 2011). Frequently, however, they are secondary to the reestablishment of blood flow following occlusion. Because of this when anticoagulants are employed so as to remove the clot, the necrotic vessels rupture and hemorrhage. Hence anticoagulants can increase the risk of secondary hemorrhagic infarction particularly when used following large strokes and/or those accompanied by gross neurological disturbances (Cerebral Embolism Study Group, 1983; Hornig et al., 2011).

ANEURYSM

Aneurysm (also called saccular or berry aneurysms) take the form of small, thin walled blisters protruding from the various cerebral arteries (Brown et al. 1991). Aneurysms may be single or multiple, and are presumed to be due to developmental defects; e.g., a congenital weakness at the junction of two arteries. Often they are located at the bifurcations and branches of various arteries, particularly the internal carotid, the middle cerebral, or the junction of the anterior communicating and anterior cerebral arteries (Adams & Victor 1994; Brown et al. 1991).


Symptoms secondary to aneurysm (due to rupture or compression) may occur at any age. Prior to rupture they are usually asymptomatic. However, as there is a tendency for them to enlarge over time, which in turn makes them more suceptible to rupture, with increasing age there is increasing risk. The peak incidence of rupture is between 40 and 55 (Adams & Victor, 1994).

Aneurysms may rupture due to sudden increases in blood pressure, while engaged in strenuous activity, during sexual intercourse, or while straining during a bowel movement (Adams & Victor, 1994). One patient I examined suffered a ruptured aneurysm when hyperventilating in his swimming pool so that he could remain submerged for a long time period.


Occasionally, if large and located near the base of the brain they may compress the optic nerves, hypothalamus or pituitary; and if within the cavernous sinus, compress the 3rd, 4th, 6th, or opthalamic division of the 5th nerve. Hence, a variety of visual, endocrine, and emotional alterations may hearld the presence of an aneurysm prior to rupture (Brown et al. 1991).

With large aneurysms, when rupture occurs, blood under high pressure may be forced into the subarachnoid space, and the patient may be striken with an excrutiating generalized headache and/or almost immediately fall unconscious to the ground, or they may suffer a severe headache but remain relatively lucid (Adams & Victor, 1994; Brown et al. 1991; Jorensen et al. 1994; Schievink et al. 2015). If the hemorrhage is confined to the subarachnoid space there are few or no lateralizing signs and no warning symptoms. In some cases, however, patient may complain of headache, transitory unilateral weakness, numbness or tingling, or speech disturbance in the days/weeks preceeding the rupture --due to minor leakage of the aneurysm.

Often those who become unconscious following rupture develop decerebrate rigidity. This is usually due to compression effects (such as herniation) on the brainstem. Persistent deep coma is accompanied by irregular respiration, attacks of extensor rigidity, and finally respiratory arrest and circulatory collapse. In mild cases, consciousness, if lost, may be regained within minutes or hours. However, patients remain drowsiness, confused, and complain of headache and neck stiffness for several days (Jorgenson et al. 1994). Unfortunately, in mild or severe cases there is a tendency for the hemorrhage to reccur.

Cerebral amyloid angiopathy

Amyloid angiopathies are associated with the development of microaneurysms and the occlusion of arteries in the superfical layers of the cerebral cortex (Kase, 2011). Following amyloid occlusion, the arteries are often weakened thus making them susceptible to rupture.

Amyloid angiopathies are often associated with recurrent hemorrhages over a period of months which in turn may lead to the develpment of intracerebral hematomas. Sometimes a head trauma can trigger these later form of hemmorhages.

<B> ARTERIOVENOUS MALFORMATIONS (AVM)

Arteriovenous malformations consist of a tangle of dilated blood vessels and are sometimes referred to as angiomas. It is a developmental abnormality, and may become symptomatic at any age, but most commonly between the ages of 20-30.

Frequently AVMs form abnormal collateral channels between arteries and veins thus bypassing the capillary system (Brown et al. 1991). When this occurs there may be an abnormal shunting of blood from the arteries to the veins. In consequence underlying brain tissue is not adequately irrigated and may become ischemic depending on the size of the AVM.

AVMs vary in size and tend to be located in the posterior portion of the cerebral hemispheres, near the surface, as well as deep within the brainstem, thalamus, and basal gnaglia. Frequently they are multiple and may be found in a variety of separate locations (Brown et al. 1991; Toole, 1990). They tend to be more common among males.

Like aneurysms, AVMs are present from birth and can grow larger and more complicated over time. It has been estimated that AVMs can increase in size by 2.8% per year and can become 56% larger over the span of a 20 year time period (Mendelow et al. 1987). As they increase in size the risk of them becoming symptomatic increases as there is a greater likelihood of collateral shunting.

AVMs are often a cause of intracerebal and subarannoid hemmorhage (Brown et al. 1991; Drake, 2008). When hemorrhage occurs blood may enter the subarachnoid space thus mimicking an aneurysm. However, although the first symptom is usually a hemorrhage, 30% of patients with this disorder may suffer a seizure and 20% headaches or focal neurological symptoms.

Small vascular malformations often become symptomatic during the 30s and 40s and occurs more often among females (Kase, 2011). These often involve the subcortical white matter of the convexity.

Brain tumors can give rise to hemorrhage in a variety of ways, particularly if the tumor is malignant and is richly vascularized. That is, certain tumors have a tendency to become spontaneously necrotic. When this occurs, there supporting vasculature ruptures. However, frequently tumors are transmitted to the brain via the arterial system, whereas others, such as carcinomas, tend to invade the walls of blood vessels. In either instance, by adhering to or penetrating the walls of the blood vessels, tumors can make them more suceptible to rupture (see chapter 34).

DRUG INDUCED HEMORRHAGES

Individuals with possible cerebrovascular abnormalities (such as aneurysm, AVM, or even tumor), and who abuse cocaine or amphetamines are at risk for suffering an intracranial hemorrhagic infarct (Golbe & Merkin, 2011; Lichtenfeld et al. 1984; Schwartz, & Cohen, 1984; Wojak & FLamm, 1987). Presumably these drug induced hemorrhages are due to transient increases in blood pressure and/or vasospasm which in turn act to rupture abnormal vessels.

LOCALIZED HEMORRHAGIC SYMPTOMS

Internal Capsule Hemorrhage

A patient who suffers an internal capsular hemorrhage is usually unconscious, pulse rate is slow, and there may be Cheyne-Stokes respiration. The head and eyes deviate to the side of the lesion (due to paralysis), and a divergent squint is common (Adams & Victor 1994). The corneal reflex is often lost opposite to the lesion, and may be lost on both sides if coma is profound. Also there is paralysis of the contralateral side of the body, and no response to pin prick on paralyzed side. The limbs are extremely hypotonic such that when lifted by the physician they will fall inertly.

Thalamic Hemorrhage

Thalamic hemorrhages also produce a hemiplegia or paresis due to compression of the adjacent internal capsule. Thalamic syndromes includes severe sensory loss from both deep and cutaneous (contralateral) receptors, and transitory hemiparesis (Adams & Victor 1994). Sensation may return to be replaced by pain and hyperatheia. Sensory deficits usually equal or outstrips the motor weakness, and an expressive aphasia may be present if the hemmorhage involves the left thalamus. The eyes may deviate downwards, with palsies of vertical and lateral gaze, and inequality of pupils with absence of light reaction.

Pontine Hemorrhage.

Hemorrhage of the pontine brainstem is usually fatal. Deep coma ensues in a few minutes and there may be total paralysis, decerebrate rigidity, and pinpoint pupils which do not react to light. The head and eyes are turned toward the side of the hemorrhage if unilateral. Usually, however, even unilateral brainstem hemorrhages exert bilateral brainstem compression (Adams & Victor 1994). Eyeballs are usually fixed.

Cerebellar Hemorrhage.

Hemorrhage involving the cerebellum usually develops over a period of hours (Adams & Victor, 1994). However, there may be sudden onset with occipital headache, vomiting, inability to stand or walk, and loss of consciousness. There is a paresis of conjugate lateral gaze to the side of the hemorrhage, and forced deviation contralaterally. Pupils are small and unequal but react to light. Also, there may be involuntary closure of one eye, as well as ocular bobbing.

Frontal, Parietal, Temporal, & Occipital Hemorrhage. <.B>

These hemorrhagic conditions initially give rise to slow or rapidly developing focal syndromes including headache (Jorgensen, et al. 1994). However, as the hemorrhage increases in size, syndromes becomes more global with impaired consciousness.

HEMORRHAGES & STROKES: ARTERIAL SYNDROMES

Internal Carotid Artery Syndromes.

Because the cerebral arteries arise from the internal carotid, hemorrhage or occlusion of this artery may be associated with extremely variable as well as widespread symptoms. As the artery becomes increasingly occluded an occasional patient may complain of hearing a disturbing noise (bruits)--a result of turbulence from stenosis of the carotid artery being relayed through the blood supply of the ear.

Stenosis of the internal caroid artery may cause massive infarction involving the anterior 2/3 of all of the cerebral hemisphere, including the basal ganglia, and can lead to death in a few days. Usually it produces a picture resembling middle cerebral artery occlusion. For example, if the left internal carotid is occluded the patient may become hemiplegic and globally aphasic. Because occlusion is accompanied by ischemia, the swelling of cerebral tissue may simulate an intracranial neoplasm. If there is massive edema, tentorial herniation and death may ensue.

Since this artery gives rise to the opthalamic which nourishes the optic nerve and retina, carotid artery insufficiency may produce transient monocular blindness just prior to stroke onset. Unilateral blindness is the only feature distinguishing the carotid syndrome from that produced by obstruction of the middle cerebral artery.

Nevertheless, since the carotid also gives rise to the middle and anterior cerebral arteries the most distal parts of the vascular territories of these vessels will suffer as they are maximally subject to the influences of ischemia. That is, the most distal portion of any occluded artery is the most severely affected. These zones are also the most vulnerable to TIAs--giving rise to weakness or paresthesias of the arm, and if extensive, the face and tongue.

In some cases of internal carotid obstruction, the numerous branches of the external carotid (occipital, superficial temporal and maxillary arteries) can serve as collateral blood supply channels. In these instances, although occluded, symptoms are mild or nonexistant.


Middle Cerebral Artery Syndromes.

The middle cerebral artery through its branches supplies the lateral part of the cerebral hemispheres, including the neocortex and white matter of the lateral/inferior frontal lobes (and motor areas), the superior and inferior parietal regions, and the superior portion of the temporal lobe (Carpenter 1991; Parent 2015). Its penetrating branches irrigate the putamen, caudate, globus pallidus, posterior limb of internal capsule and the corona radiata. Whether caused by trauma, embolus, or atherosclerosis, contralateral hemiplegia is the hallmark of infarction in the territory supplied by this artery (Adams & Victor, 2014; Absher & Toole 1996). INSERT FIGURE 12 ABOUT HERE The classic picture of total occlusion is contralateral hemiplegia, with hemiparesis involving the face and arm more than the leg. Sensory deficits may be severe or mild, with disorders of pain perception, touch, vibration, and position (Adams & Victor, 2014; Absher & Toole 1996). This includes extinction of pin-prick or touch, deficits in two-point discrimination, astereognosis, and perhaps dense sensory loss if the parietal lobe is involved. Visual field defects consists of a homonymous hemianopsia or inferior quadrantanopia.

If the left hemisphere is involved global aphasia is present. However, if the right hemisphere is effected, there may occur neglect, denial, and indifference, confabulation and manic-like states, as well as disturbances involving visual-perceptual functioning and the ability to perceive and/or express musical and emotional non-verbal nuances.

It is important to note that only a branch of this artery may be obstructed. If the posterior branch of the middle cerebral artery is occluded, the parietal and inferior parietal lobe may be affected. If the left anterior branch is occluded, the patient may develop expressive aphasia.

ANTERIOR CEREBRAL ARTERY SYNDROMES.

Through its branches the anterior cerebral artery supplies the anterior 3/4 of the medial surface of the hemispheres, including the medial-orbital frontal lobe, the anterior 4/5 of corpus collosum and the head of caudate nucleus and putamen (Carpenter 1991; Parent 2015). Hemorrhage is most often due to rupture of an aneurysm. With total occlusion or hemorrhage patients become obtunded, mute, develop grasp, sucking and snout reflexes, gait apraxia, gegenhalten, waxy flexibility, catatonic-like postures, and are incontinent (Bekson & Cummings 1991; Joseph, 1999a; Starkstein & Robinson 1992). For a further discussion of orbital and medial symptoms see Chapter 19. INSERT FIGURE 13 ABOUT HERE

VERTEBRAL-BASILAR ARTERY SYNDROMES

Because there may be collateral circulation from the vertebral-basilar system, obstruction of this artery on one side may not result in symptoms. However, if later there occurs obstruction of the opposite vertebral artery there will result disasterous consequences. Heachade occurs in over 50% of those with ischemia, beginning as a pounding or throbbing behind the orbit or in the temporal region.

A wide variety of visual and vestibular symptoms also occurs when the vertebral-basilar system is compromised including diplopia, transient blindness or blurring, and visual halucinations and illusions. Patients will complain of severe pounding or throbbing headahces (usually localized behind the orbit of the ye or in the temporal region) and will experience episodes of dizziness and vertigo, with or without hearing loss. This is because the auditory and vestibular portions of the ear as well as the brainstem vestibular nuclei are supplied by the verterbral-basilar arterial system. In addition, other brainstem signs include numbness, diplopia, impaired vision in one or both fields, dysarthria, hiccups, and difficulty swallowing (Adams & Victor 1994). INSERT FIGURE 14 ABOUT HERE

LATERAL MEDULLARY SYNDROME.

The vertebral arteries are the chief arteries of the Medulla, and supply the lower 3/4 of the pyramids, the medial lemniscus, restiform body and posterior-inferior cerebellum (Carpenter 1991; Parent 2015). However, rarely does an infarct involve the pyramids or medial lemniscus. Rather, two prominent sites of lesion are the medial and in particular the lateral medulla.

The classic lateral medullary syndrome is due to an infarction of a wedge shaped area of the lateral medulla and inferior surface of the cerebellum. Onset is associated with severe vertigo, and vomiting may occur (Adams & Victor 2014). Symptoms typically include contralateral impairment of pain and thermal sense; ipsilateral Horners syndrome (miosis, ptosis, decreased sweating); ipsilaterial paralysis of the soft palate, pharnyx and vocal cord (due to involvement of nucleus ambiguous); 9th & 10th nerve dysfunction (hoarseness, dysphagia, ipsilateral paralysis of the palate and vocal cords); loss of balance such that the patient falls to the side ipsilateral to the lesion; loss of taste sensation; hiccup, nystagmus, and nausea. There may also be dysphagia and pain or paresthesia--a sensation of hot water running over the face. There is some degree of cerebellar deficiency, with nystagmus, hypotonia, and incoordination on the side of the lesion.

MEDIAL MEDULLARY SYNDROME.

This condition is a less common consequence of vertebral artery occulsion. Nevertheless, this causes contralateral hemiparesis, ipsilateral paralysis of the tongue due to 12th nerve involvement near the zone of infarction, and loss of position and vibratory perception with sparing of pain and temperature sensation. Vertical nystagmus implies a lesion at the pontomedullary junction, and a paralysis of gaze suggests a lesion above the medulla (in pons or midbrain).

Vertebral Artery Trauma.

The vertebral arteries are vulnerable to compressions or extremes in extension such as can occur during whiplash (Toole, 1990). Moreover, if the patient suffers from osteoarthritis of the cervical spine the space through which the vertebrals pass may become narrowed thus subjecting these arteries to pinching or other stresses with movement of the head. Hence, these patients may be subject to repeated instances of vertebral insufficiency.

BASILAR ARTERY SYNDROMES.

The basilar artery supplies the pons (Carpenter 1991; Parent 2015). Infarcts characteristically involve the corticospinal and corticobullar tracts, cerebellum, cerebellar peduncles, medial/lateral lemniscus, spinothalamic tracts, and 3-8th nerves (Adams & Victor 1994). Hence, the outstanding features of basilar artery infarct are a constellation of cranial nerve signs of both the sensory and motor varieties, cerebellar symptoms, bilaterial pyramidal tract signs, including ataxia, dysarthria, hemiplegia, and disturbances involving occular movement and paralysis of gaze. If convergence is preserved the lesion is in the middle of the inferior pons. If there is no convergence the lesion is in the superior pons (medial longitudinal fasciculus).

Often patients become comotose because of ischemic compression effects on the reticular formation. Early signs of increasing occlusion or hemorrhage may occur in different combinations: somnolence, visual hallucinations, disorders of ocular movement, delerium, and korsakoffs amnesic defects.

Medial pontine lesions result in ataxia of the ipsilaterial limbs, a contralaterial paresis of the face, arm, leg, and variable sensory loss. If Horners syndrome is present or if cranial nerve 5, 7, or 8 are effected, the lesion is laterally placed. If paralysis of cranial nerve 3, 4, 6, or 7, or involvement of the pyramidal tract occurs, the lesion is probably medially placed.

In general, infarct of the medial pons results in (variably) vertigo, nausea, vomiting, nystagmus, ipsilateral ataxia, ipsilateral Horners syndrome, paresis of conjugate gaze, contralateral loss of pain and temperture sensation over the face, arm, trunk and leg, and slurred speech.

LOCKED-IN SYNDROME.

If occulsion spares the upper brainstem but involves the midpontine level, the "locked-in" syndrome may occur: the patient is alert, conscious of his surroundings, able to see and hear, but completely paralyzed and unable to communicate except through eye blinks. However, because the respiratory, vasomotor and thermoregulatory centers and pathways are affected, there might be associated abnormalities. Unfortunately, because patients can only interact via eye blinks it is extremely difficulty to ascertain how impaired the patient is in actuality.

POSTERIOR CEREBRAL ARTERY SYNDROMES.

The posterior cerebral arteries are a branch of the vertebral-basilar system and supplies via its own branches the inferomedial temporal, and medial occipital regions including areas 17, 18, 19, and the posterior hippocampus (Carpenter 1991; Parent 2015). Via deep penetrating branches it also supplies the thalamus, subthalamic nuclei, substantia nigra, midbrain, and pineal body.

Thalamic infarct or hemorrhage includes severe sensory loss and possible receptive aphasia. However, sensation may return to be replaced by pain and hyperathesia. Midbrain infarcts includes Weber syndrome (oculomotor palsy with contralateral hemiplegia) paralysis of vertical gaze, and stupor or coma (Adams & Victor 1994).

Cortical syndromes include anomia, alexia apraxia, prosopagnosia (depending on which hemisphere is involved) and related temporal-occipital, parietal-occipital disturbances. Involvement of the optic radiations or infarction of the calcarine cortex causes visual field impairments, such as scotoma and homonymous hemianopias, particularly of the upper quadrants. With bilateral occlusion the patient will become cortically blind.

Ischemic lesions in the occipital area may cause variations in the nature and form of visual field defects experienced by the patient from day to day--occasionally leading to an erroneous diagnosis of hysteria. TIAs in this vicinity are also reflected by fleeting visual field defects of a hemianopic distribution.

Distal occlusion also causes medial temporal infarction, with hippocampal involvement and memory loss. Transient global amnensia is also sometimes a consequence of transient occlusion of the posterior cerebral arteries.

CEREBELLAR ARTERY SYNDROME.

The cerebellar artery is also a branch of the vertebral-basilar system and it supplies portions of the pons as well as the cerebellum (Carpenter 1991; Parent 2015). Deafness and tinnitus may occur with lateral inferior pontine lesions due to occlusion of the anterior-inferior cerebellar artery. Infraction in this area may also cause vertigo, nystagmus, ipsilateral ataxia of limbs, and a contralateral hemiparesis with no sensory defect. With mild lesions the patient may walk with an unsteady wide based gait. With more severe lesions patients may have extreme difficulty walking or even looking to the side of the lesion, although the pupils are normal and reactive to light.

DIFFERENTIAL DIAGNOSIS: CAROTID VS. VERTEBRAL SYSTEM.

The development of deficits such as aphasia, agnosia, apraxia, constructional and manipulo-spatial deficits, emotional abnormalities and/or delusions indicate a carotid circulatory disturbance. Dizziness, diplopia, ataxia, nystagmus, cranial nerve signs, internuclear opthalmoplegia, dissociated sensory loss, and/or bilateral abnormalities are hallmarks of a brainstem lesion within the vertebral-basilar territory.

RECOVERY & MORTALITY

Mortality rates for cerebrovascular diesase have declined in the U.S. over the course of the last 40 years (Gillum, 2011; Meier & Strauman 1991). Nevertheless, the initial death rate for individuals in the acute phase and up to 30 days after stroke is about 38%. However, 50% of those who survive this phase die over the course of the next 7 years (Dombovy et al. 2011). Moreover, mortality rates increase for those who suffer strokes during the winter months (Lanska & Hoffman, 1999).

The major determinants for short-term mortality are intraventicular hemorrhage, pulmonary edeman, impaired consciousness, leg weakneness, respiratory diease and increasing age (Chambers et al. 1987; Lanska & Hoffman, 1999; Roos et al. 2015; Schievink et al. 2015)-with level of consciousnes following stroke being the single most important predictor of short-term survival (Chambers et al. 1987). The major determinants for long term mortality are low activity level, advanced age, male sex, heart disease and hypertension. However, those who suffer intraventricular hemorrhagic infarcts have a higher mortality rate than those with infarcts due to other causes (Chambers, et al. 1987; Roos et al. 2015; Schievink et al. 2015). As noted in chapter 10, those with right hemisphere damage tend to have poorer outcomes as well as higher mortality rates. In particular right parietal lobule infarcts are associated with very poor outcomes (Valdimarsson et al. 1982).

Hyperglycemia and diabetes are also associated with poor neurological recovery, and higher short-term mortality as well as increasing the risk for stroke in general. This is because diabetes and hyperglycemia both accentuate ischemic damage (Bruno et al., 1999; Pulsinelli et al. 1983; Woo et al. 2012). Hyperglycemia also appears to have a negative effect on energy metabolism due to the generation of severe lactic acidosis (Rehncrona et al. 1980) --factors which act to retard neuronal recovery.

Some authors have argued that luxury perfusion and increased cerebral blood flow (CBF) within an infarcted cite is often indicative of a good prognosis, whereas low CBF is a bad prognosis (Olsen et al. 1981). Presumably increased flow acts to nourish damaged tissue. Other studies however, indiate that initial CBF levels are not predictive of clinical outcome (Burke et al. 2011). Apparently this is because once damage occurs during the initial period of ischemia, these cells cannot be salvaged (Heiss & Rosner, 1983).

Hence, blood flow increases only when undamaged neurons return to a functionally active state (Burke et al., 2011) rather than acting to rejuvinate injured tissue. In fact, hyperperfusion may endanger neuronal recovery (Mies et al. 1983). On the otherhand oxygen metabolism seems to correlates better with clinical status and functional recovery than does blood flow (Wise et al., 1983).

Recovery is often greatest during the first 30 days after stroke (Dombovy, et al., 2011; Lind, 1982), but continues up to 6 months in some patients (Wade & Hewer, 1987). It has been estimated that although about 60% of stroke patients are able to achieve total independence in activities of daily living (Meier & Strauman 1991; Wade & Hewer, 1987) only approximately 10 to 30% of initial survivors return to their jobs without gross or obvious disability (Bekson & Cummings 1991). Depending on the nature of the stroke, about 40% demonstate mild disability, 40% are severely disabled, and 10% require institutionalization (Stallones et al, 1972; Absher & Tool, 1996).

SUMMARY

Stroke is the third most common cause of death (after heart disease and cancer) in the U.S. and Europe. Thrombosis and embolism account for approximately 75% of all strokes, whereas about 20% are due to hemorrhage. Up to 70% of all major stroke victims are usually permanently and significantly disabled (Bekson & Cummings 1991), with subarachnoid hemorrhages often resulting in sudden death (Schievink et al. 2015). Of those who survive, the five year accumulative risk of repeated stroke is about 40% in men and 25% in women, with recent evidence indicating that women are increasingly at risk for stroke and repeated stroke (secondary to heart disease) due in part to the increased incidence of female smoking.



Brain Mind Lecture 13: Brain Tumors

Brain Mind Lecture 11: Head Injuries

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DVD 1: Brain Overview

DVD 2: The Left Hemisphere, Brainstem, Midbrain, Thalamus

DVD 3: The Frontal Lobes: Frontal Lobotomy, Memory, Aphasia, Paralysis

DVD 4: The Parietal Lobes: Touch, Body-in-Space, Body Image, Hemi-Neglect, Phantom Limbs,

DVD 5: The Temporal Lobes: Language, Memory, Aphasia, Hallucinations, Face Recognition

DVD 6: The Limbic System: Amygdala, Hippocampus, Hypothalamus, Sex, Emotion, Memory, Stress, PTSD, Hallucinations