be affected, but also can produce the following symptoms: aphasia (difficulty with verbal expression, auditory comprehension, reading and writing; broca's or wernicke's area typically involved) dysarthria (motor speech disorder resulting from neurological injury) apraxia (altered voluntary movements) visual field defect memory deficits (involvement of temporal lobe) hemineglect (involvement of parietal lobe) disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe) lack of insight of his or her, usually stroke-related, disability if the cerebellum is involved, ataxia might be present and this includes: altered walking gait altered movement coordination vertigo and or disequilibrium associated symptoms loss of consciousness, headache, and vomiting usually occur more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing the brain. if symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke. causes thrombotic stroke illustration of an embolic stroke, showing a blockage lodged in a blood vessel in thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower than that of a hemorrhagic stroke. a thrombus itself (even if it does not completely block the blood vessel) can lead to an embolic stroke (see below) if the thrombus breaks off and travels in the bloodstream, at which point it is called an embolus. two types of thrombosis can cause stroke: large vessel disease involves the common and internal carotid arteries, the vertebral artery, and the circle of willis. diseases that may form thrombi in the large vessels include (in descending incidence): atherosclerosis, vasoconstriction (tightening of the artery), aortic, carotid or vertebral artery dissection, various inflammatory diseases of the blood vessel wall (takayasu arteritis, giant cell arteritis, vasculitis), noninflammatory vasculopathy, moyamoya disease and fibromuscular dysplasia. small vessel disease involves the smaller arteries inside the brain: branches of the circle of willis, middle cerebral artery, stem, and arteries arising from the distal vertebral and basilar artery. diseases that may form thrombi in the small vessels include (in descending incidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as a result of high blood pressure and aging) and fibrinoid degeneration (a stroke involving these vessels is known as a lacunar stroke) and microatheroma (small atherosclerotic plaques). anemia causes increase blood flow in the blood circulatory system. this causes the endothelial cells of the blood vessels to express adhesion factors which encourages the clotting of blood and formation of thrombus. sickle-cell anemia, which can cause blood cells to clump up and block blood vessels, can also lead to stroke. a stroke is the second leading cause of death in people under 20 with sickle-cell anemia. air pollution may also increase stroke risk. embolic stroke an embolic stroke refers to an arterial embolism (a blockage of an artery) by an embolus, a traveling particle or debris in the arterial bloodstream originating from elsewhere. an embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectious endocarditis). because an embolus arises from elsewhere, local therapy solves the problem only temporarily. thus, the source of the embolus must be identified. because the embolic blockage is sudden in onset, symptoms usually are maximal at the start. also, symptoms may be transient as the embolus is partially resorbed and moves to a different location or dissipates altogether. emboli most commonly arise from the heart (especially in atrial fibrillation) but may originate from elsewhere in the arterial tree. in paradoxical embolism, a deep vein thrombosis embolizes through an atrial or ventricular septal defect in the heart into the brain. causes of stroke related to the heart can be distinguished between high and low-risk: high risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of the mitral or aortic valve disease, artificial heart valves, known cardiac thrombus of the atrium or ventricle, sick sinus syndrome, sustained atrial flutter, recent myocardial infarction, chronic myocardial infarction together with ejection fraction <28 percent, symptomatic congestive heart failure with ejection fraction <30 percent, dilated cardiomyopathy, libman-sacks endocarditis, marantic endocarditis, infective endocarditis, papillary fibroelastoma, left atrial myxoma and coronary artery bypass graft (cabg) surgery. low risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramen ovale (pfo), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale, left ventricular aneurysm without thrombus, isolated left atrial "smoke" on echocardiography (no mitral stenosis or atrial fibrillation), complex atheroma in the ascending aorta or proximal arch. among those who have a complete blockage of one of the carotid arteries, the risk of stroke on that side is about one percent per year. a special form of embolic stroke is the embolic stroke of undetermined source (esus). this subset of cryptogenic stroke is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. about one out of six ischemic strokes could be classified as esus. cerebral hypoperfusion cerebral hypoperfusion is the reduction of blood flow to all parts of the brain. the reduction could be to a particular part of the brain depending on the cause. it is most commonly due to heart failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. because the reduction in blood flow is global, all parts of the brain may be affected, especially vulnerable "watershed" areas—border zone regions supplied by the major cerebral arteries. a watershed stroke refers to the condition when the blood supply to these areas is compromised. blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur. venous thrombosis cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds the pressure generated by the arteries. infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke. intracerebral hemorrhage it generally occurs in small arteries or arterioles and is commonly due to hypertension, intracranial vascular malformations (including cavernous angiomas or arteriovenous malformations), cerebral amyloid angiopathy, or infarcts into which secondary hemorrhage has occurred. other potential causes are trauma, bleeding disorders, amyloid angiopathy, illicit drug use (e.g., amphetamines or cocaine). the hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into the ventricular system, csf or the pial surface. a third of intracerebral bleed is into the brain's ventricles. ich has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoid hemorrhage (which technically may also be classified as a type of stroke). other other causes may include spasm of an artery. this may occur due to cocaine. silent stroke a silent stroke is a stroke that does not have any outward symptoms, and people are typically unaware they have had a stroke. despite not causing identifiable symptoms, a silent stroke still damages the brain and places the person at increased risk for both transient ischemic attack and major stroke in the future. conversely, those who have had a major stroke are also at risk of having silent strokes. in a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the united states. approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent mri infarcts or hemorrhages. silent strokes typically cause lesions which are detected via the use of neuroimaging such as mri. silent strokes are estimated to occur at five times the rate of symptomatic strokes. the risk of silent stroke increases with age, but may also affect younger adults and children, especially those with acute anemia. pathophysiology ischemic histopathology at high magnification of a normal neuron, and an ischemic stroke at approximately 24 hours on h&e stain: the neurons become hypereosinophilic and there is an infiltrate of neutrophils. there is slight edema and loss of normal architecture in the surrounding neuropil. ischemic stroke occurs because of a loss of blood supply to part of the brain, initiating the ischemic cascade. atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow by causing the formation of blood clots within the vessel or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a consequence of atrial fibrillation, or in the carotid arteries, break off, enter the cerebral circulation, then lodge in and block brain blood vessels. since blood vessels in the brain are now blocked, the brain becomes low in energy, and thus it resorts to using anaerobic metabolism within the region of brain tissue affected by ischemia. anaerobic metabolism produces less adenosine triphosphate (atp) but releases a by-product called lactic acid. lactic acid is an irritant which could potentially destroy cells since it is an acid and disrupts the normal acid-base balance in the brain. the ischemia area is referred to as the "ischemic penumbra". after the initial ischemic event the penumbra transitions from a tissue remodeling characterized by damage to a remodeling characterized by repair. as oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy phosphate compounds such as adenosine triphosphate (atp) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. this sets off a series of interrelated events that result in cellular injury and death. a major cause of neuronal injury is the release of the excitatory neurotransmitter glutamate. the concentration of glutamate outside the cells of the nervous system is normally kept low by so-called uptake carriers, which are powered by the concentration gradients of ions (mainly na+) across the cell membrane. however, stroke cuts off the supply of oxygen and glucose which powers the ion pumps maintaining these gradients. as a result, the transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing glutamate into the extracellular space. glutamate acts on receptors in nerve cells (especially nmda receptors), producing an influx of calcium which activates enzymes that digest the cells' proteins, lipids, and nuclear material. calcium influx can also lead to the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to programmed cell death. ischemia also induces production of oxygen free radicals and other reactive oxygen species. these react with and damage a number of cellular and extracellular elements. damage to the blood vessel lining or endothelium may occur. these processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. however, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs. collateral flow impact of collateral flow on clot lysis and reperfusion the brain can compensate inadequate blood flow in a single artery by the collateral system. this system relies on the efficient connection between the carotid and vertebral arteries through the circle of willis and, to a lesser extent, the major arteries supplying the cerebral hemispheres. however, variations in the circle of willis, caliber of collateral vessels, and acquired arterial lesions such as atherosclerosis can disrupt this compensatory mechanism, increasing the risk of brain ischemia resulting from artery blockage. the extent of damage depends on the duration and severity of the ischemia. if ischemia persists for more than 5 minutes with perfusion below 5% of normal, some neurons will die. however, if ischemia is mild, the damage will occur slowly and may take up to 6 hours to completely destroy the brain tissue. in case of severe ischemia lasting more than 15 to 30 minutes, all of the affected tissue will die, leading to infarction. the rate of damage is affected by temperature, with hyperthermia accelerating damage and hypothermia slowing it down and various other factors. prompt restoration of blood flow to ischemic tissues can reduce or reverse injury, especially if the tissues are not yet irreversibly damaged. this is particularly important for the moderately ischemic areas (penumbras)