Cerebrovascular Disease

Cerebrovascular refers to blood flow within the brain. Cerebrovascular disease includes all disorders in which an area of the brain is temporarily or permanently affected by bleeding or lack of blood flow. Cerebrovascular diseases included stroke, carotid stenosis, vertebral stenosis and intracranial stenosis, aneurysms and vascular malformations. Restrictions in blood flow may occur from vessel narrowing (stenosis), clot formation (thrombosis), blockage (embolism), or blood vessel rupture (hemorrhage). Lack of sufficient blood flow (ischemia) affects brain tissue and may cause a stroke.

Cerebrovascular Disease Statistics

Stroke is the third leading cause of death in the United States. Of the more than 700,000 people affected every year, about 500,000 of these are first attacks, and 200,000 are recurrent. About 25 percent of people who recover from their first stroke will have another stroke within five years. Stroke is a leading cause of serious long-term disability. Each year, an estimated 30,000 people in the United States experience a ruptured cerebral aneurysm and as many as 6 percent may have an unruptured aneurysm.

Cerebrovascular Diagnostic Tests

The majority of cerebrovascular problems can be identified through diagnostic imaging tests. These tests allow vascular specialists to view the arteries and vessels in and around the brain and the brain tissue. Cerebral angiography: Arteries are not normally seen in an X-ray, so contrast dye is used to view them. The patient is given a local anesthetic, the artery is punctured, usually in the leg, and a needle is inserted into the artery. A catheter (a long, narrow, flexible tube) is inserted through the needle and into the artery. It is then threaded through the main vessels of the abdomen and chest until it is properly placed in the arteries of the neck. This procedure is monitored by a fluoroscope (a special x-ray that projects the images onto a TV monitor). The contrast dye is then injected into the neck area through the catheter, and x-ray pictures are taken. Carotid duplex (doplar ultrasound): In this procedure, ultrasound is used to help detect plaque, blood clots, or other problems with blood flow in the carotid arteries. There are no known risks and this test is noninvasive and painless. CT Scan: A diagnostic image created after a computer reads x-rays. In some cases, a medication will be injected through a vein to help highlight brain structures. Bone, blood and brain tissue have very different densities and can easily be distinguished on a CT scan. A CT scan is a useful diagnostic test for hemorrhagic strokes because blood can easily be seen.

However, damage from an ischemic stroke may not be revealed on a CT scan for several hours or days and the individual arteries in the brain cannot be seen. CTA allows clinicians to see blood vessels of the head and neck and is increasingly being used instead of an invasive angiogram. Electroencephalogram (EEG): A diagnostic test using small metal discs (electrodes) placed on a persons scalp to pick up electrical impulses. These electrical signals are printed out as brain waves. Lumbar puncture (spinal tap): An invasive diagnostic test that uses a needle to remove a sample of cerebrospinal fluid from the space surrounding the spinal cord. This test can be helpful in detecting bleeding caused by a cerebral hemorrhage. Magnetic Resonance Imaging (MRI): A diagnostic test that produces three-dimensional images of body structures using magnetic fields and computer technology. It can clearly show various types of nerve tissue and clear pictures of the brain stem and posterior brain. MRI of the brain can help determine whether there are signs of prior mini-strokes. This test is noninvasive, although some patients may experience claustrophobia in the imager. Cerebral Magnetic Resonance Angiogram (MRA): This is a noninvasive study which is conducted in a Magnetic Resonance Imager (MRI). The magnetic images are assembled by a computer to provide an image of the arteries located in a patients head and neck. The MRA shows the actual blood vessels in the neck and brain and can help detect blockage and aneurysms. Back to the Top

Stroke
Stroke is an abrupt interruption of the constant blood flow to the brain that causes loss of neurological function. The interruption of blood flow can be caused by a blockage, leading to the more common ischemic stroke, or by bleeding in the brain, leading to the more deadly hemorrhagic stroke. Ischemic stroke constitutes an estimated 80 percent of all stroke cases. Stroke may occur suddenly, sometimes with little or no warning, and the results can be devastating.

Stroke Symptoms
Warning signs may include some or all of the following symptoms, which are usually sudden: Dizziness, nausea or vomiting Unusually severe headache Confusion, disorientation or memory loss Numbness, weakness in an arm, leg or the face, especially on one side

 Abnormal or slurred speech Difficulty with comprehension Loss of vision or difficulty seeing Loss of balance, coordination, or the ability to walk

Types of Stroke and Treatment

Ischemic Stroke Ischemic stroke is the most common type of stroke, accounting for a large majority of strokes. There are two types of ischemic stroke: thrombotic and embolic. A thrombotic stroke occurs when a blood clot, called a thrombus, blocks an artery to the brain and stops blood flow. An embolic stroke occurs when a piece of plaque or thrombus travels from its original site and blocks an artery. The materials that has moved is called an embolus. How much of the brain is damaged or affected depends on exactly how far downstream in the artery the blockage occurs. Hemorrhagic Stroke A hemorrhagic stroke can be caused by hypertension, rupture of an aneurysm or vascular malformation, or as a complication of anticoagulation medications. An intracerebral hemorrhage occurs when there is bleeding directly into the brain tissue, which often forms a clot within the brain. A subarachnoid hemorrhage occurs when the bleeding fills the cerebrospinal fluid spaces around the brain. Both conditions are very serious. Hemorrhagic stroke usually requires surgery to relieve intracranial pressure caused by bleeding. Surgical treatment for hemorrhagic stroke caused by an aneurysm or defective blood vessel can prevent additional strokes. Surgery may be performed to seal off the defective blood vessel and redirect blood flow to other vessels that supply blood to the same region of the brain. Recovery and rehabilitation are important aspects of stroke treatment. In some cases, undamaged areas of the brain may be able to perform functions that were lost when the stroke occurred. Rehabilitation includes physical therapy, speech therapy and occupational therapy. Regardless of what type of stroke has been suffered, it is vital that victims receive emergency medical treatment as soon as possible for the best possible outcomes to be realized. Transient Ischemic Attack (TIA) A TIA is a temporary cerebrovascular event that leaves no permanent damage. Usually it entails an artery to the brain is temporarily blocked, causing stroke-like symptoms, but the blockage dislodges before any permanent damage occurs. Symptoms of a TIA may be similar to a stroke, but they resolve quickly. In fact, symptoms may be so vague and fleeting that people just brush them off, especially when they last just a few minutes. TIA symptoms include: Sudden numbness or weakness of the face, arm or leg, especially on one side of the body Sudden confusion, trouble speaking or understanding Sudden trouble seeing in one or both eyes

 Sudden trouble walking, dizziness, loss of balance or coordination Sudden, severe headache with no known cause While there is no treatment for the TIA itself, it is essential that the source of the TIA be identified and appropriately treated before another attack occurs. If you experience TIA symptoms, seek emergency medical help immediately. About 30 percent of all people who suffer a major stroke experience a prior TIA, and 10 percent of all TIA victims suffer a stroke within two weeks. The quicker you seek medical attention, the sooner a diagnosis can be made and a course of treatment started. Back to the Top

Risk Factors
Although they are more common in older adults, strokes can occur at any age. Stroke prevention can help reduce disability and death caused by the disease. Controllable or treatable risk factors for stroke include: Smoking High blood pressure Carotid of other artery disease History of TIAs Diabetes High blood cholesterol Physical inactivity and obesity Receiving hormone replacement therapy

Uncontrollable risk factors include:

Age: People of all ages, including children, have strokes. But the older you are, the greater your risk of stroke. Gender: Stroke is more common in men than in women. Heredity or race: You have a greater risk of stroke if a parent, grandparent, sister or brother has had a stroke. African-Americans have a much higher risk of death from a stroke than Caucasians, partly because they are more prone to having high blood pressure, diabetes and obesity. Prior stroke or heart attack: If you have had a stroke, you are at much higher risk of having another one. If you have had a heart attack, you are also at higher risk of having a stroke.

Carotid Stenosis

The carotid arteries supply oxygen-rich blood to your brain. Plaque forms when the internal carotid arteries become blocked by fat and cholesterol buildup.

Medical Treatment
Treatment is determined by the extent of the narrowing and the condition of the patient. For many people with arteries narrowed less than 50 percent, medication is prescribed to help reduce the risk of ischemic stroke. These include medications to control high blood pressure, reduce cholesterol levels, and anticoagulants to thin the blood and prevent it from clotting.

Surgery
Carotid endarterectomy is a procedure in which the surgeon makes an incision in your carotid artery and removes the plaque using a dissecting tool. Removing the plaque is accomplished by widening the passageway, which helps to restore normal blood flow. Your artery will be repaired with sutures or a patch. The entire procedure usually takes about one or two hours. Back to the Top

Carotid Angioplasty and Stenting

An alternative form of treatment is available for patients who may be at too high of a risk to undergo surgery. Carotid stenting is a procedure in which a tiny, slender metal-mesh tube is fitted inside your carotid artery to increase the flow of blood blocked by plaque. The stent is inserted after an angioplasty procedure, in which the doctor guides a balloon-tipped catheter into your blocked artery. The balloon is inflated and pressed against the plaque, flattening it and reopening the artery. The stent acts as scaffolding to prevent the artery from collapsing or from closing up again after the procedure is completed.

Cerebral Aneurysms
A cerebral (or cranial) aneurysm is an area where a blood vessel in the brain weakens, resulting in a bulging or ballooning out of part of the vessel wall. Usually, aneurysms develop at the point where a blood vessel branches, because the fork is structurally more vulnerable. The disorder may result from congenital defects or from other conditions such as high blood pressure, atherosclerosis (the buildup of fatty deposits in the arteries), or head trauma. Aneurysms occur in all age groups, but the incidence increases steadily for individuals age 25 and older, is most prevalent in people ages 50 to 60, and about three times more prevalent in

women. The outcome for patients treated before a ruptured aneurysm is much better than for those treated after, so the need for adequate evaluation of patients suspected of having a cerebral aneurysm is very important. Unruptured cerebral aneurysms can be detected by noninvasive measures, include MRA and a carotid angiogram. A rupture can be detected by a CT scan or lumbar puncture. If these tests suggest the presence of an aneyrysm, formal cerebral angiography may be performed. People who suffer a ruptured brain aneurysm may have some or all of these warning signs: localized headache, nausea and vomiting, stiff neck, blurred or double vision, sensitivity to light (photophobia), or loss of sensation. Many people with unruptured brain aneurysms have no symptoms. Others might experience some or all of the following symptoms, which may be possible signs of an aneurysm: cranial nerve palsy, dilated pupils, double vision, pain above and behind eye, and localized headache. When cerebral aneurysms rupture, they usually cause bleeding in the brain, resulting in a interacranial hematoma (a blood clot).. Blood can also leak into the cerebrospinal fluid (CSF) or areas surrounding the brain and cause a subarachnoid hemorrhage. Blood can irritate, damage, or destroy nearby brain cells. This may cause problems with bodily functions or mental skills. In more serious cases, the bleeding may cause brain damage, paralysis or coma. Ruptured brain aneurysms are fatal in about 50 percent of cases.

Surgery
An operation to "clip" the aneurysm is performed by doing a craniotomy (opening the skull surgically), and isolating the aneurysm from the bloodstream using one or more clips, which allows it to deflate. Surgical repair of cerebral aneurysms is not possible if they are located in unreachable parts of the brain. Angiography is used to visualize closure of the aneurysm and preserve normal flow of blood in the brain. A less invasive technique which does not require an operation, called endovascular therapy, uses micro catheters to deliver coils to the site of the enlarged blood vessel that occludes (closes up) the aneurysm from inside the blood vessel. A procedure called balloon assisted coiling uses a tiny balloon catheter to help hold the coil in place. A procedure called combination stent and coiling utilizes a small flexible cylindrical mesh tube that provides a scaffold for the coiling. Aneurysms may be treated with endovascular techniques when the risk of surgery is too high. While the best method of securing the aneurysm should be made on an individual basis, in general, patients with a ruptured cerebral aneurysm should be treated as soon as possible. Surgical risks and outcomes depend on whether or not the aneurysm has ruptured, the size and location of the aneurysm, and the patients age and overall health. Post-surgical complications can include vasospasm and hydrocephalus. Vasospasm is a sudden constriction of a blood vessel that reduces the blood flow. Hydrocephalus is a condition in which

excess cerebrospinal fluid (CSF) builds up within the ventricles (fluid-containing cavities) of the brain and may increase pressure within the head. Back to the Top

Vascular Malformations
The term vascular malformation refers to an abnormal connection of an artery, vein, or both. These include malformations of normal veins or arteries leading directly to veins. Vascular malformations are formed as the blood vessels in the brain develop during pregnancy, but the direct cause is unknown.

Arteriovenous malformations (AVMs)

An AVM is a tangle of abnormal and poorly formed blood vessels (arteries and veins), with a higher rate of bleeding than normal vessels. AVMs can occur anywhere in the body, but brain AVMs present substantial risks when they bleed. Dural AVMs occur in the covering of the brain, and are an acquired disorder that may be triggered by an injury. AVMs are usually diagnosed through a combination of MRI and angiography. AVMs can irritate the surrounding brain and cause seizures or headaches. Left untreated, AVMs can enlarge and rupture, causing intracerebral or subarachnoid hemorrhage and permanent brain damage. Every year, about four out of every 100 people with an AVM will experience a hemorrhage. Preventing the rupture of vascular malformations is one of the major reasons that early neurosurgical treatment is recommended for AVMs. A treatment plan is devised to offer the lowest risk, yet highest chance of obliterating the lesion. The three types of treatment available include direct removal using microsurgical techniques, stereotactic radiosurgery, and embolization using neuroendovascular techniques. Although microsurgical treatment affords the opportunity for immediate removal of the AVM, some AVMs may best be treated by a combination of therapies. Stereotactic radiosurgery is a minimally invasive treatment that uses computer guidance to concentrate radiation to the malformed vessels of the brain. This radiation causes abnormal vessels to close off. Unfortunately, stereotactic radiosurgery is usually limited to lesions less than 3.5 cm in diameter, and may take up to two years to completely obliterate the lesion. Embolization uses neuroendovascular techniques to guide tiny catheters into the small cerebral vessels of the brain that feed the AVM. Once the catheter reaches the core of the AVM, liquid glue or particles can be injected to occlude portions of the AVM or its feeding arteries. Neuroendovascular therapy can make subsequent surgical removal of an AVM safer, or can reduce the size of an AVM to a volume in which radiosurgery offers a higher efficacy.

Moyamoya disease
Moyamoya disease is a progressive disease of the carotid arteries and their major branches that can lead to irreversible blockage. The name comes from the Japanese word for a "puff of smoke" due to the appearance of the lesions that form. In fact, it affects people of Japanese origin far more commonly than the rest of the population. It is a disease that tends to affect children and adults in the third to fourth decades of life. Children with the disease may have strokes, TIAs, slowly progressive cognitive decline, seizures, or involuntary movements of the extremities. Adults more commonly experience intracranial hemorrhages as a result of the disease. There are several surgeries that have been developed for the condition, but currently the most favored are: EDAS, EMS, STA-MCA and multiple burr holes. The EDAS (encephaloduroarteriosynangiosis) procedure requires dissecting a scalp artery over a length of several inches and then making a small temporary opening in the skull directly beneath the artery. The artery is then sutured to the surface of the brain and the bone replaced. In EMS (encephalomyosynangiosis) surgery, the temporalis muscle, which is in the temple region of the forehead, is dissected and through an opening in the skull, placed onto the surface of the brain. Other operations include: the STA-MCA (superficial temporal artery-middle cerebral artery) in which a scalp artery is directly sutured to a brain surface artery; and a procedure in which multiple small holes (burr holes) are placed in the skull to allow for growth of new vessels into the brain from the scalp.

Venous angiomas
Patients with venous angiomas may have headaches or seizures, although these symptoms may be unrelated to the angiomas. More commonly, these lesions are asymptomatic and are identified when patients are being evaluated for other conditions. They rarely bleed, so treatment is usually not necessary. They affect approximately 2 percent of the general population.

Vein of Galen malformation (VGM)

A far rarer malformation is the VGM, sometimes detected in prenatal testing, or through heart failure in infants. Occurring during embryonic development, a VGM is an abnormal connection between arteries and the deep draining veins of the brain. Under normal conditions, these arteries and veins are connected by capillaries that function to slow blood flow through the brain, allowing for the necessary exchange of oxygen and nutrients. A VGM has a thicker wall than an AVM and is unlikely to rupture and bleed. However, because a VGM does not have capillaries, the blood may flow extremely fast, putting excessive strain on

the heart, which may result in cardiac failure. It is very important that children suffering from this condition be evaluated and diagnosed by experts so that appropriate treatment measures are taken. Embolization is the method of choice for treating patients with VGMs. For more information about the treatment of cerebrovascular disease, call LifeBridge Health at 410-601-WELL (9355). Back to the Top

Cerebrovascular disease is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. Hypertension is the most important cause; it damages the blood vessel lining, endothelium, exposing the underlying collagen where platelets aggregate to initiate a repairing process which is not always complete and perfect. Sustained hypertension permanently changes the architecture of the blood vessels making them narrow, stiff, deformed, uneven and more vulnerable to fluctuations in blood pressure. A fall in blood pressure during sleep can then lead to a marked reduction in blood flow in the narrowed blood vessels causing ischemic stroke in the morning. Conversely, a sudden rise in blood pressure due to excitation during the daytime can cause tearing of the blood vessels resulting in intracranial hemorrhage. Cerebrovascular disease primarily affects people who are elderly or have a history of diabetes, smoking, or ischemic heart disease. The results of cerebrovascular disease can include a stroke, or occasionally a hemorrhagic stroke. Ischemia or other blood vessel dysfunctions can affect the person during a cerebrovascular accident.

Classification
A transient ischemic attack (TIA) leaves little to no permanent damage within the brain. The symptoms of this include facial weakness, visual impairment, loss of coordination, or balance and a sudden headache. Severe blockage of the arteries to the brain is known as carotid stenosis. This generally results from high head trauma.

[edit] Stroke
Main article: Stroke Carotid artery effects retina, cerebral hemisphere, or both. Retinal Transient blackouts; the sense of a shade pulled over the eyes. Cerebral Contralateral (opposite sided) paralysis of a single body part; paralysis of one side of the body; localized tingling, numbness; hemianopic visual loss; aphasia (loss of speech); rare loss of consciousness. Vertebrobasilar Bilateral visual disturbance including dim, gray, or blurred vision or temporary total blindness; diplopia (double vision). Labyrinth/medulla Vertigo; unsteadiness; nausea; vomiting. Brainstem Slurring dysarthria (tongue weakness causing impaired speech); dysphagia (difficulty swallowing); numbness, weakness; all four limb paresthesia; drop attacks from sudden loss of postural tone are basilar in

origin; a vertebrobasilar artery occlusion episode causes symptoms to be induced by abrupt position changes.

[edit] Causes
Cerebrovascular disease can be divided in to embolism, aneurysms, and low flow states depending on its cause. Major modifiable risk factors include hypertension, smoking, obesity, and diabetes.

[edit] Pathophysiology
In a healthy, anatomical structure of the body, the carotid arteries form the main blood supply to the brain. Following a stroke, voluntary control of the muscles may be lost, depending on the type of stroke the victim is encountering. Strokes can also result from embolism or due to a ruptured blood vessel. Embolism blocks small arteries within the brain, causing dysfunction to occur. Spontaneous rupture of a blood vessel in the brain causes a hemorrhagic stroke. Another form of cerebrovascular disease includes aneurysms. In females with defective collagen, the weak branching points of arteries give rise to protrusions with a very thin covering of endothelium that can tear to bleed easily with minimal rise of blood pressure. This can also occur with defective capillaries caused by tissue cholesterol deposition especially in hypertensive subjects with or without dyslipidemia. If bleeding occurs in this process, the resulting effect is a hemorrhagic stroke in the form of subarachnoid hemorrhage, intracerebral hemorrhage or both. In the main structure, the carotid arteries overspread the majority of the cerebrum. The common carotid artery divides into the internal and the external cartoid arteries. The internal carotid artery becomes the anterior cerebral artery and the middle central artery. The ACA transmits blood to the frontal parietal and a small part of the occipital lobe. The MCA is the largest branch of the internal carotid artery. From the Basillar artery are two posterior cerebral arteries. Branches of the Basillar and PCA supply the occipital lobe, brain stem, and the cerebellum. Ischemia is the loss of blood flow to the focal region of the brain. The beginning process of this is quite rapid. The duration of a stroke is usually two to fifteen minutes. One side of the face, hand, or arm may swell up. During this time, the person may lose conscious control and faint. Brain deficits may improve over a maximum of 72 hrs. Deficits do not resolve in all cases. The neurological recovery period includes stable, to improving, brain function. Stable is the period by which neither nutrient supply is regained, nor is it lost. Improving, depending on a hospital code, generally means that the arteries gain control and blood flow functions consistently within the brain. The cartoid arteries connect to the vertebral arteries. These branch off into the cerebellar and posterior meningenial arteries, which supply the back of the brain. Also, during ischemia, interneurons weaken, causing an insufficient amount to perform vital functions to be present. The neuroglis become congested or maintain loss during a cerebrovascular accident. If impulse amount ceases, then life itself will cease and the victim may

enter the stage of clinical death. Neural pathways weaken, therefore decreasing action potential. The neural arc, which in general consists of sensory and motor neurons, weaken as well. The muscles become paralyzed, in some cases for life. Paralysis also includes the weakening of the receptors in the body, unless improvement is made. Cerebrovascular damage to the brain is what makes it difficult for receptors to receive the impulse and transmit it of a neuron. This chemical reaction is then transmitted creating a poor reflex to the body. The meninges that also protect the brain and spinal cord are deeply weakened, allowing the victim to suffer vast transmission of diseases or unstable growth or maintenance if the victim is not in resting position. During the stage of paralysis, the spinal tracts do not have much to do with the enduring condition of cerebrovascular disease, either, in time may shorten the life of a victim who is suffering because the nutrient supply is weakened in transmission during cerebrovascular disease. Descending and ascending tracts will generally be cut off during cerebrovascular disease, which conduct impulses down from the cord of the brain. This is known as anesthesia in a minor case. In a healthy body, the cerebrospinal fluid (also known as CSF) may also weaken the cortoid plexus, into a network of brain capillaries. Certain types of hydrocephalus ("water" or CSF on the brain) may be treated by using a shunt (medical) or a cerebral shunt, which involves inserting a hollow tube (or the shunt) through a blocked channel so the CSF can be used to be drained to another portion of the body. The dermatomes are a skin surface area which is regulated by the spinal cord. During a stroke, these may be damaged.

__ Atherosclerotic middle cerebral artery stenosis is a rare but potentially devastating cause of cerebral ischemia and stroke. While medical management remains the mainstay for stroke prevention, surgical and/or endovascular intervention is indicated in selected patients. This article reviews the role of surgery and endovascular techniques in the treatment of middle cerebral artery stenosis based on its natural history, pathophysiology, and prognosis when treated medically. Atherosclerotic disease of the middle cerebral artery (MCA) is a relatively rare condition, occurring in only 7 to 8% of patients presenting with stroke in the MCA distribution.1,2,3 Subsequent MCA stenosis or occlusion may lead to transient ischemic attacks (TIAs) or frank stroke, thus prompting the need for intervention. This article reviews the surgical and endovascular management options for atherosclerotic MCA stenosis based on its natural history, pathophysiology, and prognosis after medical treatment. __

I. INTRODUCTION Cerebrovascular disease (CVD) includes all disorders in which an area of the brain is transiently or permanently affected by ischemia or bleeding and one or more of the cerebral blood vessels are involved in the pathological process.

CVD is the third leading cause of death after heart disease and malignancy and it is estimated that an average of 500,000 new strokes will occur each year in the USA. CVD is the most disabling of all neurologic diseases. Approximately 50% of survivors have a residual neurologic deficit and greater than 25% require chronic care. Stroke incidence and mortality are declining primarily due to the successful treatment of HTN and control of risk factors.

II. CLASSIFICATION OF CEREBROVASCULAR DISEASE

III. ISCHEMIC/EMBOLIC STROKE A. ANATOMY 1. Carotid Artery distribution-carotid arteries perfuse the majority of the cerebrum Common Carotid Artery-->splits into the Internal Carotid Artery and the External Carotid Artery, then the Internal Carotid Artery-->divides into the Anterior Cerebral

Artery (ACA) and the Middle Cerebral Artery (MCA); both a left and right side are present a. ACA-supplies the medial surface of the frontal lobe, parietal lobe and occipital lobe b. MCA-the largest branch of the internal carotid artery 2. Vertebrobasilar Artery distribution-perfuses base of cerebrum and majority of cerebellum 2 Vertebral Arteries-->join to form the Basilar Artery-->branching from the Basilar Artery are the 2 Posterior Cerebral Arteries (PCA) a. Basilar Artery and PCA-supply the occipital lobe, brain stem and cerebellum

B. CLASSIFICATION OF ISCHEMIC EVENTS (These are based on the temporal course and eventual outcome.) 1. Transient Ischemic Attacks (TIAs) a. episodes of a temporary reduction in perfusion to a focal region of the brain causing a short-lived disturbance of function b. the patient experiences a temporary focal neurological deficit such as slurred speech, aphasia, amaurosis fugax (monocular blindness), or weakness or paralysis of a limb

c. onset is rapid; usually onset is less than 5 minutes d. duration usually 2-15 minutes; can last up to 24 hours e. symptoms (vary depending on the CNS anatomy involved)

1. sensation of swelling or numbness of the hand, arm, or one side of the face or
tongue 2. loss of strength in an arm, hand or leg 3. difficulties in speaking or reading

f. no neurological deficit remains after the attack g. one episode in a lifetime to > 20 in one day h. may be the only warning of an impending stroke 2. Reversible Ischemic Neurological Deficit (RIND) a. focal brain ischemia in which the deficit improves over a maximum of 72 hours b. deficits may not completely resolve in all cases 3. Cerebral Infarction a. permanent neurological disorder; the patient presents with fixed deficits b. can present in 3 forms: 1. stable-the neurological deficit is permanent and will not improve or deteriorate 2. improving-return of previously lost neurological function over several days to weeks 3. progressing-the neurological status continues to deteriorate following the initial onset of focal deficits; may see a stabilization period, followed by further progression C. PATHOPHYSIOLOGY 1. Atherosclerosis and subsequent plaque formation results in arterial narrowing or occlusion and is the most common cause of arterial stenosis. 2. Thrombus formation is most likely to occur in areas where atherosclerosis and plaque deposition have caused the greatest narrowing of vessels. 3. Platelet Aggregation

a. exposed subendothelium after injury to vessel b. vessel collagen is exposed to blood triggering "activation" of platelets c. release of ADP from activated platelets causes platelet aggregation d. consolidation of platelet-plug by RBCs, coagulation factors, and formation of fibrin network e. Thromboxane A2 (TX A2) is produced by platelets and endothelium promoting platelet aggregation and vasoconstriction 4. Coagulation Cascade a. a series of enzyme complexes located on the surface of platelets and endothelium which lead to thrombin production b. Thrombin (IIa) then converts Fibrinogen to Fibrin D. CLINICAL PRESENTATION Clinically, symptoms depend on the area of cerebral circulation affected and on the extent to which it is affected. 1. Internal Carotid Artery occlusion: a. no characteristic clinical picture b. may range from a TIA to infarction of a major portion of the ipsilateral (on the same side) hemisphere c. if adequate intracranial collateral circulation is present, may see no signs or symptoms d. Neurological symptoms:

1. monoparesis to hemiparesis with or without a defect in vision

2. impairment of speech or language 3. transient monocular blindness

2. Middle Cerebral Artery occlusion: a. most occlusions in the first portion of this artery are due to emboli and typically produce a neurological deficit b. opportunity for collateral circulation is restricted to anastomotic blood flow from the anterior and posterior cerebral arteries on the surface of the brain

c. Neurological symptoms:

1. hemiplegia (paralysis of one side of the body)

2. hemisensory deficit 3. hemianopsia (blindness in 1/2 of the visual field) 4. aphasia (if infarct is in the dominant hemisphere)

3. Anterior Cerebral Artery occlusion: a. Neurological symptoms:

1. weakness of the opposite leg with or without sensory involvement

2. apraxia (particularly of gait) 3. possible cognitive impairment

4. Vertebrobasilar system: a. Neurological symptoms:

1. severe vertigo, nausea, vomiting, dysphagia, ipsilateral cerebellar ataxia

2. decreased pain and temperature discrimination 3. diplopia, visual field loss, gaze palsies

E. RISK FACTORS 1. Hypertension-most important risk factor for all stroke types; no defined BP indicating increased stroke risk, but risk increases proportionately as BP increases. 2. Heart Disease

a. CHF
b. c. d. e.

CAD AFib Rheumatic Heart Disease LVH

3. TIAs, prior stroke, carotid bruits 4. Increased hematocrit, increased fibrinogen 5. Sickle Cell Disease 6. Lifestyle Factors

a. Age (older)

b. c. d. e. f.

Alcohol abuse Cigarette smoking Drug abuse Genetic factors Males

7. Diabetes Mellitus 8. Migraine HAs 9. Retinal emboli IV. TREATMENT OF CEREBROVASCULAR DISEASE A. GOALS OF THERAPY 1. Stroke prevention through risk-factor reduction. 2. Prevention of initial or recurrent stroke by modifying the underlying pathologic process. 3. Reduction of secondary brain damage by maintaining adequate perfusion to marginally ischemic areas and decreasing edema. B. TREATMENT OF TRANSIENT ISCHEMIC ATTACKS 1. Eliminate or control risk factors. 2. Education of patient regarding risk-factor reduction and signs and symptoms of TIAs and mild stroke. 3. Surgical Interventions a. Carotid Endarterectomy (CEA)

1. surgical removal of the atheromatous plaque

2. reserved for patients with an ulcerated lesion or clot that occludes > 70% of

blood flow in the carotid artery 3. may decrease risk of stroke by 60% over the two years following the procedure 4. vertebral endarterectomy no longer used 4. Endovascular procedures a. Balloon Angioplasty

1. consists of placing a small deflated balloon in the stenosed vessel

2. the balloon is then inflated pressing the atheromatous plaque against the wall 3. has a risk of dislodging emboli that can be carried to the brain or retina

b. Stent Placement

1. experimental procedure
wall of artery

2. consists of placing a stainless steel coil into the vessel which then sticks to

5. Antiplatelet Agents a. Aspirin 1.Mechanism of Action

a. inhibition of platelet aggregation

the platelet (5-7 days)

b. decreases release of vasoactive substances from platelets c. irreversible inactivation of platelet cyclooxygenase; effect lasts for the life of

2. Efficacy

a. ASA has shown clinically significant reductions (22-24%) in stroke risk and
b. c. d. e.

death in randomized trials in patients who have experienced a previous TIA or stroke (secondary prevention) doses have ranged from 50 to 1500 mg/day more recent trials have evaluated lower doses (30 to 325 mg/day); results indicate that lower doses may be as beneficial with less adverse effects some studies suggest that ASA is more effective in men than in women (due to small number of women in studies??) role in primary prevention unclear

b. Dipyridamole (PERSANTINE) 1. Mechanism of Action

a. weak inhibitor of platelet aggregation

b. inhibits platelet phosphodiesterase

2. Efficacy

a. clinical trials have not supported the use of dipyridamole in cerebral ischemia
b. no additive effect found with aspirin

c. Sulfinpyrazone (ANTURANE)

1. Mechanism of Action

a. reversible inhibition of cyclooxygenase

2. Efficacy

a. clinical trials have not supported use

d. Ticlopidine (TICLID) 1. Mechanism of Action

a. inhibits ADP-induced platelet aggregation

thrombin c. bleeding time prolonged d. minimal effect on cyclooxygenase 2. Efficacy

b. inhibits platelet aggregation induced by collagen, PAF, epinephrine and

a. has been shown to reduce the incidence of stroke by approximately 22% in

b. c. d. e.

patients who have experienced previous TIAs or stroke may be more effective than aspirin with less GI effects no gender difference seen with ticlopidine as with ASA dosed at 500 mg/day divided into 2 doses (250 mg PO BID) adverse effects:

1. diarrhea 2. rash 3. increased total serum cholesterol (ratio of HDL:TChol unchanged) 4. neutropenia occurred in 1-2% of patients; must monitor CBC every 2 weeks for the first 3 months of therapy RECOMMENDATIONS

A. ASA has been proven to be beneficial in the secondary prevention of TIAs and
in decreasing major cerebrovascular events and death; however, the correct dosage is still unknown. B. The currently recommended dose of aspirin is 325-975 mg/day. C. The role of aspirin in the primary prevention of TIAs and stroke is still unclear.

D. Ticlopidine has been proven to be effective in the secondary prevention of

TIAs and stroke. Due to side effects and cost, it should be reserved for those patients who fail or cannot tolerate ASA.

6. Anticoagulation a. Warfarin 1. no studies that prove the superiority of anticoagulants over antiplatelet agents 2. may reduce the risk of stroke in patients with a prior MI 3. may be useful in those patients who continue to be symptomatic despite antiplatelet therapy 4. the major exception is in patients with cerebral embolism of cardiac origin a. chronic anticoagulation with warfarin has been shown to prevent cerebrovascular events in patients with NVAF b. INR adjusted to between 2.0-3.0 C. Treatment of Acute Cerebral Infarction/Ischemic Stroke 1. Accurate diagnosis is key! A CT Scan must be done to rule out a hemorrhagic stroke before initiation of any treatment.

a. most patients do not have impaired consciousness in the first 24 hours

hypoxia or increased intracranial pressure

b. if consciousness is impaired, suspect a stroke-related seizure, hemorrhage,

2. Supportive care

a. Maintain adequate tissue oxygenation: May require airway support and

b. c. d. e. f.

ventilatory assistance. Check for possible aspiration pneumonia. BP: In most cases, BP should not be lowered. If severe HTN, lower BP cautiously as neurological status may worsen when BP is lowered. Volume status: Correct for hypovolemia and keep electrolytes in the normal range. Fever: treat and look for source of fever. Hypoglycemia/hyperglycemia: Keep under control. Hyperglycemia may worsen the ischemic injury. DVT Prophylaxis: This is a must as stroke patients have a high risk for DVT! It is important to use either sc heparin 5,000 IU q. 8 or 12 hrs. or sc enoxaparin 30 mg q. 12 hrs. plus early ambulation!

3. Pharmacologic Therapy

a. Recombinant Tissure Plasminogen Activator (r-tPA) Protocol--(For Select

Patients Only!!) 1. efficacy is influenced by the length of time between the onset of the stroke and the initiation of treatment 2. rapid diagnosis and immediate administration of tPA increases its efficacy and may limit the potential for hemorrhagic conversion of ischemic stroke 3. Inclusion Criteria:

a. ischemic stroke within 3 hours

b. SBP < 185; DBP < 110

4. Exclusion Criteria:

a. isolated neurological deficit

b. c. d. e. f.

another stroke or serious head injury within the previous 3 months INR > 1.7 use of heparin in the prior 48 hours major surgery in the prior 14 days platelet count < 100,000/mm3

5. tPA dose:

a. 0.9 mg/kg body weight; max. dose 90 mg

infusion over 1 hour

b. give 10% of the dose as a bolus over 1-2 minutes and the rest as a continuous c. No antiplatelets or anticoagulants within 24 hours!!

6. Results:

a. improved outcome with regard to disability and death that persists 3 months
b. there is a higher incidence of intracerebral hemorrhage (6.4% vs. 0.6%) b. Intra-arterial Thrombolysis

after therapy

1. early clot lysis and recanalization in about 50% of the patients with intra-arterial streptokinase and urokinase

2. intra-arterial r-pro UK 6 mg given within 6 hours of the stroke resulted in a 58% recanalization rate vs. 14% with placebo 3. main concern is hemorrhagic transformation of the ischemic lesion 4. risk of bleeding may increase with concomitant heparin 5. should still be considered investigational until further data collected

c. Heparin
1. useful for progressing stroke; questionable role in stable or improving stroke 2. dosing: 50-70 U/kg as a loading dose, followed by 10-25 U/kg/hour; goal PTT 1.5-2.0X control 3. may opt to not use a loading dose in these patients 4. major concerns are conversion of an ischemic stroke into a hemorrhagic stroke secondary to heparin, bleeding and thrombocytopenia 5. careful selection of patients is important

d. Low-Molecular Weight Heparin (LMWH)

1. Org 10172 has been studied in acute stroke patients 2. synthetic low-molecular-weight fraction of heparin 3. undergoing investigation in several clinical trials 4. less risk of hemorrhage(?) and thrombocytopenia(?) 5. cannot be recommended for treatment until the results of an ongoing multicenter study are reported

e. Ancrod (ARVIN)
1. derived from the venom of the Malayan pit viper snake 2. enzyme that breaks down fibrinogen to a soluble ancrod-fibrin complex without allowing stabilization of fibrin (fibrin is not cross-linked) 3. may stimulate tPA activation from vascular endothelium 4. causes fibrinolysis soon after administration; low risk of hemorrhagic complications

5. dose: 0.5 U/kg in NS over 6 hours; administered for 7 days following stroke in the clinical trials; titrate to a fibrinogen level of 0.5-1.0 g/L 6. cannot recommend for use until further clinical trials are completed; role in therapy not yet established 4. Investigational Therapies for Acute Ischemic Stroke

a. Dextran Infusion
1. decreased blood viscosity by volume expansion 2. decreased platelet function 3. decreased blood interaction with endothelium

b. Prostacyclin
1. potent vasodilator and platelet suppressant 2. has fibrinolytic activity

c. Calcium Channel Blockers

1. may increase CBF by smooth muscle relaxation 2. may preserve neuronal function by preventing the calcium influx into neurons that occurs during ischemia 3. nimodipine 30 mg PO every 6 hours for 28 days used in clinical trials; nicardipine also evaluated 4. role in therapy not fully known at this time; seems to work best if initiated within 6-8 hours of symptom onset

d. Hemodilution
1. utilize albumin and fluids to decrease hematocrit to 30- 35% which decreases blood viscosity 2. questionable role in therapy

e. 21-Aminosteroids (Tirilazad Mesylate-FREEDOX)

1. during ischemia, free radicals are formed which initiate lipid peroxidation

2. 21-aminosteroids are potent inhibitors of lipid peroxidation 3. doses up to 6.0 mg/kg/day divided into 4 doses IV x 5 days have been shown to be beneficial in clinical trials 4. role in therapy not yet defined; studies still ongoing V. HEMORRHAGIC STROKE (SAH) Subarachnoid hemorrhage occurs in approximately 26,000 North Americans per year. Most patients range in age from 20-70 years old; however, SAH occurs most frequently in those who are 50-60 years old. The initial hemorrhage is fatal in 20-30% of patients and will ultimately be fatal in 50% of patients. SAH causes permanent neurological disability in 20-50% of survivors. Two-thirds of patients with successful aneurysm clipping never return to the same quality of life as before the SAH. Unlike other types of cerebrovascular diseases, the incidence of SAH has remained about the same for the last 20 years. A. PATHOPHYSIOLOGY 1. SAH occurs when blood is released into the subarachnoid space surrounding the brain and spinal cord. B. ETIOLOGY 1. trauma 2. ruptured intracranial aneurysms (75-80%)

a. Associated with disorders such as congenital weakening of blood vessels,

bacterial or fungal infections and hypertension. b. The walls of the cerebral blood vessels become weak and an aneurysm forms. c. Blood can leak out slowly if the vessel wall is fragile or rapidly if the aneurysm ruptures. The escape of blood into the subarachnoid space causes irritation and damage to brain tissue. 3. arteriovenous malformation (AVM) (4-5%)

a. An abnormal collection of blood vessels where arterial blood flows directly

into draining veins. 4. vasculitis 5. tumor 6. anticoagulants

7. coagulation disorders (ie. hemophilia) 8. no known cause (14-22%) C. RISK FACTORS FOR SAH 1. hypertension 2. cigarette smoking (3-10X greater risk than in nonsmokers) 3. oral contraceptive use/estrogen use 4. alcohol consumption (binge drinking) 5. pregnancy and parturition/straining exercises 6. drug abuse (cocaine) D. CLINICAL PRESENTATION 1. Symptoms

a. severe headache-"the worst headache of my life"

b. c. d. e. f.

nausea and vomiting neck pain nuchal rigidity photophobia, diplopia seizures

2. Grading of the severity of SAH

a. relates to the clinical status of the patient and to the outcome

b. Hunt and Hess Scale frequently used in clinical practice c. Hunt and Hess Scale for Rating Severity of SAH

1. Grade I -----minor headache, minor neck stiffness 2. Grade II ----severe headache, severe neck stiffness, cranial nerve signs, photophobia 3. Grade III ---drowsiness, confusion, mild paresis, mild dysphagia 4. Grade IV ---stuporous, moderate to severe hemiparesis, dysphagia 5. Grade V ----coma, decerebrate rigidity, symptoms of acute midbrain syndrome 3. Diagnosis

a. Computed Tomography (CT Scan)-used to demonstrate the presence of blood

in the subarachnoid space. b. Lumbar Puncture (LP)-look for bloody CSF that does not clear. c. Angiography-used to establish the presence of an aneurysm and precisely locate it for surgery. E. COMPLICATIONS AND TREATMENT MEASURES IN SAH 1. Rebleeding

a. Usually occurs within 2 weeks of the SAH; however, the maximal frequency of
rebleeding is in the first day after SAH. 70% mortality.
b. Rebleeding within 2 days occurs in 20% of patients and is associated with 60c. The cause is usually due to rupture of the clot that surrounds the original d. Symptoms

hemorrhage site.

1. sudden onset of severe headache 2. rapid rise in BP 3. decreased level of consciousness

e. Prevention of Rebleeding
1. General

a. Avoid anticoagulants and antiplatelet drugs including salicylates,

nonsteroidal anti-inflammatory drugs, ticlopidine, heparin and warfarin. b. Avoid rapid reduction of intracranial pressure. c. Keep BP low, but avoid a rapid reduction. 2. Surgery

a. Early surgery-surgical intervention within 3 days of SAH. Eliminates the risk

of rebleeding and removal of the clot may decrease the risk of delayed cerebral ischemia. b. Late surgery-intervention more than 3 days after SAH. 3. Antifibrinolytic Therapy (controversial)

a. Aminocaproic acid (Amicar)-blocks activation of plasminogen to plasmin and

inhibits the activity of plasmin on the fibrin clot.

b. Dose: 5 grams IV bolus, followed by a continuous infusion of 1-2 gms/hour for

14-21 days

2. Hydrocephalus

a. May develop within 1 day or may be delayed for weeks after the initial

hemorrhage. The risk of hydrocephalus is associated with the volume and location of blood within the subarachnoid space and ventricular system. b. Acute hydrocephalus occurs within 24 hours of the initial hemorrhage and causes a decreased level of consciousness and focal neurological deficits. Late hydrocephalus causes dementia, gait disturbances, and incontinence. c. Treatment of Hydrocephalus 1. Surgery

a. Surgery is the only treatment for hydrocephalus.

b. A drain is placed to allow CSF to flow outward. 1. External Ventricular Drain (EVD) 2. Intraventricular Shunt to the peritoneum (VPS) 3. Intraventricular Shunt to the aorta (VAS)

3. Delayed Cerebral Ischemia (secondary to vasospasm)

a. Primary cause of permanent neurological deficits.

b. Cerebral vasospasm develops in 20-40% of patients during the 2-3 weeks

following a SAH and most commonly develops 5-12 days after the initial hemorrhage. c. The cause is not well understood; however, it may result from compromised autoregulation causing portions of the brain to become ischemic. It may also result from vasoactive substances that are released from degrading red blood cells (epinephrine, serotonin, and oxyhemoglobin) which may cause arterial narrowing. d. Treatment of Delayed Cerebral Ischemia 1. Volume expansion and induction of hypertension ("Triple H Therapy"-hydration, hypertension, hemodilution)

a. Volume expansion: 0.9% NaCl and 5% serum albumin solutions are used.

Endpoint is to maintain PAWP of 15-20 mmHg without causing pulmonary edema. b. Induction of hypertension: Dopamine and norepinephrine are used to elevate BP. The goal is to elevate SBP to 200-220 mmHg and maintain it for 7 to 14 days.

2. Calcium Channel Blockers (Nimodipine and Nicardipine)

a. Mechanism of Action
1. May improve clinical outcome by limiting fixed neurological deficits. 2. May inhibit the rapid influx of calcium into ischemic neurons and prevent 3. May dilate penetrating blood vessels allowing blood to be shunted back to

calcium-induced damage.

ischemic areas of the brain and re-establish some autoregulation of cerebral blood flow.

b. Dose

Nimodipine 60 mg PO/NGT every 4 hours for 21 days. Must be initiated within 3 days of SAH. 3. Angiography with Papaverine

a. Papaverine, a non-selective muscle relaxant, is injected intra-arterially

directly at the site of vasospasm. It is still considered experimental. 4. Angioplasty 4. Seizures

a. Occur in 5 to 15% of patients with SAH.

b. Prevention of Seizures

1. Anticonvulsants

a. Phenytoin is preferred acutely as there is an IV dosage form available and it

b. Dose

has minimal effects on mental status.

1. Loading Dose: 15-20 mg/kg 2. Maintenance Dose: 5-7 mg/kg/day, based on side effects and serum concentrations

c. If patients do not experience a seizure, may discontinue the anticonvulsant

d. Phenobarbital and Valproic Acid are alternative agents. http://emedicine.medscape.com/article/323120-overview

after 3-12 months.