Cerebrovascular Disease

Overview of Cerebrovascular Diseases

Introduction o predominates in the middle and late years of life rd o causes approx. 200,000 deaths in the US each year as well as considerable neurologic disability; 3 leading killer in US o these diseases cause either ischemia-infarction (85-90%) or intracranial hemorrhage (10-15%) o morbidity and mortality from cerebrovascular diseases has been diminishing in recent years, due largely to better recognition and treatment of the underlying arterial and cardiac diseases, including hypertension o Co-morbidity of atherosclerotic disease: CAD, cerebrovascular disease, PAD o Risk Factors: Non-modifiable age, family history, sex; modifiable smoking, DM, hyperlipidemia, HTN, obesity o Stroke permanent neurological deficits caused by ischemic damage from thromboemboli to the retina or brain o Frequency of complete stroke: atherothrombotic (61%); cerebral embolus (24%); intracerebral hemorrhage (7%); sub-arachnoid hemorrhage (7%) o most cerebrovascular diseases present as the abrupt onset of a focal neurologic deficit the deficit may remain fixed, or it may rapidly improve or progressively worsen o this abrupt onset of nonconvulsive and focal neurologic deficit is referred to as stroke or cerebrovascular accident (CVA) Classification Of Cerebrovascular Diseases: o (1) Cerebral Ischemia-Infarction: Thrombotic occlusion and embolic occlusion (artery to artery and cardiogenic) Cerebral ischemia is caused by a reduction in blood flow that lasts for several seconds or a few minutes. If the cessation of flow lasts for more than a few minutes, infarction of brain tissue results. Generalized reduction in cerebral blood flow due to systemic hypotension (e.g., cardiac arrhythmia, myocardial infarction, or hemorrhagic shock) usually produces syncope, infarction in the border zones between the major cerebral artery distributions, or widespread brain necrosis, depending on the duration of hypotension FOCAL ischemia or infarction, on the other hand, is usually caused by disease in the cerebral vessels themselves or by emboli from a proximal arterial source or the heart. Four Causes Of Ischemic Stroke (1) Thrombosis (53%): Atherosclerosis, vasculitis, arterial dissection, hematologic disorders Thrombotic strokes occur without warning symptoms in 80-90%. 10-20% are heralded by one or more transient ischemic attacks (TIAs). Thrombotic strokes often present with stuttering and fluctuating symptoms that worsen over several minutes or hours. (2) Embolism (35%): can be cardiac source or atherothrombotic arterial source Embolic strokes usually present with a neurologic deficit that is maximum at onset (3) Vasoconstriction: Vasospasm and reversible cerebral vasoconstriction (4) Venous: Dehydration, pericranial infection, postpartum and postoperative states, systemic cancer o (2) Intracranial Hemorrhage: Intracerebral, Subarachnoid, Subdural (usually traumatic), and Epidural (traumatic) Subdural and epidural hematomas are usually the result of trauma, not cerebrovascular disease the majority of intracerebral hemorrhages are associated with hypertension Subarachnoid hemorrhage (SAH) is usually due to a ruptured saccular aneurysm or, less commonly, an arteriovenous malformation

Cerebral Ischemia-Infarction
General Pathophysiology Of Cerebral Ischemia And Infarction: o within 10 sec after cerebral blood flow ceases: metabolic failure of brain tissue and EEG shows slowing of electrical activity if the circulation is immediately restored abrupt and complete recovery of function if persists for a few minutes neuronal injury with restoration of flow, recovery of function takes several min/hr and may be incomplete. In addition, during the circulatory failure, the blood elements may sludge, the capillary endothelium may swell, and the blood flow may not reestablish itself, even when primary cause of the flow failure is corrected (the "no-reflow" phenomenon) o more prolonged periods of ischemia frank tissue necrosis Cerebral edema follows and progresses over the subsequent 2 to 4 days if the region of infarction is large, edema may produce considerable mass effect with its attendant consequences o decreased CO decreased cerebral blood flow ischemic (border zone areas most vulnerable watershed areas) o causes of cerebral ischemia and infarction are atherosclerosis with thromboembolism and cardiogenic embolism Atherosclerotic Ischemia and Infarction o Atherosclerosis is maximal at arterial bifurcations, and it commonly affects the origin of the internal carotid artery in the neck and the origin of major and minor arterial branches inside the head o atherosclerotic plaques can cause an arterial stenosis that produces a hemodynamic obstruction to flow. If this regional in cerebral blood flow falls below a critical level, it will cause a transient or permanent ischemic event. o artery-to-artery emboli important cause of retinal and hemispheric ischemia and infarction. When an atherosclerotic plaque on the arterial wall ulcerates, the necrotic material may dislodge and serve as emboli or may provide a surface on which aggregation of platelets and coagulation of fibrin occurs. The resulting fibrin clot also may dislodge into the arterial circulation, or it may enlarge and produce thrombotic occlusion of the artery o Lacunar infarcts are small infarcts in the deep white matter of the hemisphere or brainstem. Due to HTN-induced lipohyalinosis or arteriosclerosis of small penetrating arteries

although the exact cause of ischemia or infarction in a given patient with atherosclerosis is not always known, the primary abnormality is clearlyatherosclerosis with its complicating lesion, the fibrous plaque. The plaque may result in stenosis or ulceration, with subsequent thrombosis orembolization Clinical Manifestations Of Ischemic Stroke o typical ischemic stroke presents with the abrupt onset of a focal neurologic deficit o A TIA is manifested by a neurologic deficit lasting < 24 h (usually 5 to 20 min). It is often referred to as a mini-, warning, or transient stroke, because itquickly resolves but often portends an impending stroke. The deficit is focal and confined to an area of the brain perfused by a specific artery. o mechanisms for TIAs are: (1) low flow in an artery due to tight stenosis or occlusion (2) embolism from heart, proximal arterial/atherosclerotic plaque debris, thrombus o any obstructive vascular process in extra- or intracranial arteries can cause low-flow TIA if collateral flow to potentially ischemic brain is also impaired, and can lead to arterial thrombosis; if symptoms persist >24 hrs, infarction has occurred o TIAs are highly predictable for stroke risk of stroke is 33% within 5 yrs of last TIA; also age and frequency of TIAs increase risk (>5 TIAs in 2 wks 20% have stroke in 3 months, and 30% in 6 months) o Internal Carotid Artery Disease attacks of transient monocular blindness; TIAs; frequent unaccustomed headaches; associated history of CAD or PVD; neck brui ts, retinal infarcts or cholesterol plaques o ACA (anterior cerebral artery) stroke: contralateral hemiplagia o Posterior circulation (large vessel disease): cranial nerve dysfunction; cerebellar involvement; Horner syndrome; ANS nuclei and tracts; abnormal respiratory control; altered LOC; corticospinal, spinothalamic involvement o Reversible ischemic neurologic deficit (RIND) is an infrequently used term that defines an ischemic event in which the deficit usually recovers over a 24- to 72-h period, but which may take as long as 1 week to resolve o Completed stroke (cerebral infarction) of the thrombotic type is generally nonhemorrhagic. It typically evolves to its maximal deficit within a few hours. Often, patient awakens with a completed deficit. A completed stroke is sometimes heralded by one or more TIAs in preceding days/weeks/months, most likely whe n tight arterial stenosis is causative. o In progressing stroke, or stroke-in-evolution, the focal ischemia worsens from min to min or hr to hr. There are usually stepwise incremental increases in neurologic deficit occurring over a several-hour period. While there may be several pathogenic mechanisms producing a progressing stroke, one such mechanism appears to be a thrombus-in-evolution, with a thrombus extending from its site of origin in a primary artery and progressively obliterating collateral branches, thereby interfering with anastomotic vessels. o the hallmark presentation is the abrupt onset of a hemiparesis in an individual in the atherosclerotic age group. Lacunar Disease o lacunar infarction refers to infarction following atherothrombotic or lipohyalinotic occlusion of one of the penetrating branches of the circle of Willis, middle cerebral artery stem, or vertebral and basilar arteries. o deficit evolves gradually with frequent fluctuations and progression o Pathophysiology the middle cerebral artery stem, the arteries comprising the circle of Willis, and basilar and vertebral arteries all give rise to 100- to 300- m diameter branches that penetrate the deep gray and white matter of the cerebrum or brainstem each of these small branches can thrombose either by atherothrombotic disease at its origin or by the development of lipohyalinotic thickening. Thrombosis of these vessels causes small infarcts that are referred to as lacunes HTN (also DM) is principal risk factor for such small-vessel disease. Lacunar infarcts cause ~20% of all strokes. Penetrating and branch artery disease subintimal foam cells and deposition of fibrinoid material within vessel walls, therefore NO penumbrum (no collateral flow); whorles, tangles of connective tissue o Syndromes pure motor hemiparesis, dysarthria-clumsy hand, pure sensory deficit (thalamic syndrome), and sensory-motor strokes Laboratory And Imaging Evaluation o accurate diagnosis is based largely on the history and examination, supplemented by judicious use of blood tests and imaging of the brain [CT and MR imaging (MRI)] and its blood vessels (arterial Doppler ultrasonography, MRA (magnetic resonance angiogram) and x-ray angiography, and invasive angiogram (gold standard)) o electrocardiogram (ECG) may demonstrate conduction abnormalities and arrhythmias or reveal evidence of recent MI o CT scan will often demonstrate an area of infarction and will confirm or exclude the presence of an intracerebral, subdural, or epidural hemorrhage or other mass lesion. Moreover, it may demonstrate large aneurysms and AVMs and subarachnoid or intraventricular blood. o A lumbar puncture (LP) will confirm or exclude subarachnoid hemorrhage or meningitis due to syphilis or other chronic infections. An LP should not be performed on patients with intracranial mass lesions o MRI scanning is the most sensitive method to detect embolic infarction st nd rd o Ex: large MCA infarct 1 step is CT 2 MRI of brain 3 diffusion weighted MRI (shows abnormal perfusion) Treatment and Prevention o of the atherosclerosis factors, hypertension is of the greatest importance. In general, all HTN should be treated. o General Measures: avoid hyperglycemias; nutrition support; normothermia; dVT prophylaxis; infection prevention; seizure control; maintain fluid and electrolyte balance o Blood Pressure management (decrease BP below 180 SBP before therapy) o Other Therapeutic Options: (1) Antiplatelet agents: Platelet antiaggregation agents prevent atherothrombotic events, including TIA and stroke. They inhibit the formation of intraarterial platelet aggregates that can form on diseased arteries, induce thrombus formation, and occlude the artery or embolize into the distal circulation. Aspirin and ticlopidine are used most. Aspirin Its antiplatelet effect is accomplished by acetylating the cyclooxygenase enzyme in platelets. This irreversibly inhibits the formation in platelets of thromboxane A2, a platelet aggregating and vasoconstricting prostaglandin. Aspirin also inhibits the formation in endothelial cells of prostacyclin, an antiaggregating and vasodilating prostaglandin. Ticlopidine (and clopidogrel bisulfate) blocks the ADP receptor on platelets and thus prevents the cascade resulting in activation of the glycoprotein IIb/IIIa receptor that leads to fibrinogen binding to the platelet and consequent platelet aggregation. Ticlopidine is more effectivethan aspirin. Side effects: neutropenia, diarrhea, and skin rash Dipyridamole is an antiplatelet agent that acts by inhibiting platelet phosphodiesterase, which is responsible for the breakdown of cyclic AMP. The resulting elevation in cyclic AMP inhibits aggregation of platelets (2) Anticoagulation therapy: Heparin (ie nadroparin) is widely used for "unstable TIA " (i.e., crescendo or recent-onset TIA)

if long-term anticoagulation is chosen, warfarin is administered. (3) Surgical therapy: carotid endarterectomy, microsurgery, neuroendovascular, stereotactic radiosurgery surgery for atherosclerotic occlusive disease is largely limited to carotid endarterectomy for plaques located at the origin of the internal carotid artery in the neck; clamp off arteries make incision clean out plaque stitch up surgery in the proximal common carotid, the subclavian, and the vertebral arteries is uncommon. anastomosing extracranial scalp arteries to major intracranial arteries to bypass inoperable obstructions in the internal carotid artery is of no value. Stenosis < 50% antiplatelet therapy; no benefit with surgery Stenosis 50-70% usually surgical benefit; individualize to patient Stenosis >70% surgery benefits Asymptomatic patients and stenosis > 60% carotid endarterectomy provides absolute risk reduction of 5.8% over 5 yrs; relative risk reduction of 55% (decrease risk from 2% to 1% so not as overwhelming as it looks); no effect shown in women, only helpful for men Neuroendovascular therapy minimally invasive surgery carotid artery stenting; no more effective than surgery (4) Angioplasty and stenting HHH therapy (HTN, hemodilution, hypervolemia) present with vasospasms, thus BP and flow to areas of brain Treatment (Acute management) o when cerebral infarction occurs, the immediate goal is to optimize cerebral perfusion of the ischemic area o Thrombolysis lyse the clot o t-PA: give if within 3 hrs of deficit; IV administer if within 6 hrs anti-coagulant do not give to patients with hemorrhage or people with signs of infarct on CT may increase chance of hemorrhage Pathology o cerebral infarcts may be pale (nonhemorrhagic) or red (hemorrhagic). o Vascular congestion of varying degree is common in all infarcts, but extravasation of blood is usually associated with embolic infarcts. o because emboli migrate and lyse, recirculation into the infarcted brain may cause petechial hemorrhages. o sometimes there is enough seepage of blood into the infarct to cause visible hemorrhagic infarction on a CT scan. o infarcts in the distribution of small, penetrating arteries leave small cavities or lacunes (lacunar infarcts), whereas major arterial occlusions produce a wide area of necrosis that leaves a large, fluid-filled cavity in the brain. o Edema invariably accompanies the tissue necrosis. In small infarcts it may be relatively insignificant. In large infarcts, however, massive edema compresses adjacent tissue and adds to the ischemic process; it also increases intracranial pressure and may cause herniation of the brain from one intracranial compartment to another.

Intracranial Hemorrhages
Intracerebral Hemorrhage o most common type of nontraumatic intracranial hemorrhage. Important cause of stroke, esp. in Asians and blacks. o hypertension and cerebral amyloid angiopathy cause the majority of these hemorrhages. Minor causes tumors and vascular malformations o advanced age and heavy alcohol consumption increase the risk. Cocaine-induced hemorrhage is one of the most important causes in the young. o Symptoms headaches plus something else o Causes of Intracranial Hemorrhage: Spontaneous intracerebral hemorrhage (hypertensive, amyloid angiopathy); Ruptured arteriovenous malformation (saccular, mycotic); Ruptured aneurysm; Cocaine, amphetamines; Trauma; Bleeding with brain tumors; Systemic bleeding disorders, including anticoagulation therapy; Hemorrhagic infarction o Pathophysiology And Pathology intracerebral hemorrhage usually results from spontaneous rupture of a small penetrating artery deep in the brain. the most common sites are: (1) the basal ganglia (putamen, thalamus, and adjacent deep white matter) (2) the deep cerebellum (3) the pons the small arteries in these areas seem most prone to hypertension-induced vascular injury the leak may be small, or a large clot may form and compress adjacent tissue, causing herniation and death rupture or seepage into the ventricular system often occurs; primary intraventricular hemorrhage is rare if the patient survives, the clot liquefies, is absorbed, and leaves only a small residual cleft most hypertensive intracerebral hemorrhages develop over 30 to 90 min, whereas those associated with anticoagulant therapy may evolve for as long as 24 to 48 h. Once bleeding stops, it generally does not start again. Within 48 h macrophages begin to phagocytize the hemorrhage at its outer surface. After 1 to 6 months, the hemorrhage is generally resolved. Morbidity 88% disability; 33% mortality very deadly disease o Prevention: Hypertension is the leading cause of primary cerebral hemorrhage. Prevention is primarily aimed at reducing hypertension, excessive alcohol use, and use of illicit drugs such as cocaine and amphetamines. o Treatment (Acute Management) ~75% with a hypertensive intracerebral hemorrhage die. Size/location of the hematoma determines prognosis. surgical evacuation of hematoma in certain instances indications for surgery are uncertain! Mannitol (osmotic agent) intracranial pressure that has been raised by the volume of the hematoma and edema Subarachnoid Hemorrhage o the commonest cause of spontaneous SAH is a ruptured saccular aneurysm; can occur any time after adulthood

other causes bleeding from an AVM or extension into the subarachnoid space from a primary intracerebral hemorrhage Pathophysiology And Pathology Saccular aneurysms occur at the bifurcations of the large arteries at the base of brain and rupture into subarachnoid space in the basal cisterns ~85% of aneurysms occur on the anterior circulation (15% in posterior circulation), mostly on the circle of Willis. o Clinical Manifestations Aneurysms can undergo small ruptures and leaks of blood into the subarachnoid space, so-called warning leaks Sudden unexplained headache at any location should raise suspicion of SAH At the moment of aneurysmal rupture with major SAH, the intracranial pressure suddenly rises. Abrupt, severe, and generalized vasospasm may occur transiently. These events may account for the sudden transient loss of consciousness that occurs in nearly half of patients the hemorrhage is not the problem, the increased intracranial pressure is!! (if it continues to increase, on perfusion to brain) the headache (usually generalized) is often called by the patient "the worst headache of my life." Vomiting is common and when coupled with sudden headache should always raise the suspicion of SAH. o Diagnosing headaches differentiating from SAH sentinel: sudden onset; no history of headaches most likely to be SAH tension: bilateral pain; contraction of neck or pericranial muscles; no neurologic events migraine: history of headache; gradual onset; visual disturbance; nausea; throbbing quality cluster: unilateral pain; no visual/cerebral symptoms; facial erythema; rhinorrhea; brief o Laboratory And Imaging Evaluation (The hallmark of aneurysmal rupture is blood in CSF) CT scan confirms 95% of SAHs if scan negative, or headache for > 4 days; lumbar puncture indicated the extent and location of subarachnoid blood on CT scan help locate the underlying aneurysm and identify the cause of any neurologic deficit. The clot also will help predict delayed vasospasm. A noncontrast CT scan should be done first, because on an enhanced scan normal arteries in the basal cisterns may be mistaken for clotted blood. LP prior to scanning is indicated only if a CT scan is not available at the time of the suspected SAH. Once the diagnosis of hemorrhage from ruptured saccular aneurysm has been established, four-vessel angiography (both carotids and vertebrals) is generally performed to localize and define the anatomic details of the aneurysm and to determine if other unruptured aneurysms exist. Treatment: endovascular surgery (put platinium coils into the aneurysm); gamma knife surgery Arteriovenous Malformation o Vascular malformations, or angiomas, may be tiny and cryptic or massive anomalies that cause headaches, brain damage, seizures, and hemorrhages o AVMs are the most important vascular malformations of the nervous system and consist of a tangle of abnormal vessels forming an abnormal communication between the arterial and venous systems o Most are developmental arteriovenous fistulas in which the involved vessels enlarge with the passage of time. o AVMs vary in size from a small blemish a few millimeters in diameter to a huge mass of tortuous channels. o Hypertrophic and dilated arterial feeders approach the main lesion, disappear below the cortex, and break up into a network of thin-walled blood vessels that connect directly with draining veins. These often form huge, dilated, pulsating channels carrying away arterial blood. o the blood vessels forming the tangle interposed between arteries and veins are usually abnormally thin. o AVMs occur in all parts of the brain, brainstem, and spinal cord, but the largest ones are most fr equently in the posterior half of the hemispheres; AVMs are more frequent in men o the chief clinical symptoms and signs are headache, seizures, and those associated with rupture. o AVMs less than 0.5 cm in diameter are usually low-pressure venous angiomas that bleed infrequently and minimally o If they bleed, surgical or gamma-knife resection or obliteration should be considered. o Lobar pattern of hemorrhage on CT scan o Treatment: endovascular or gamma knife surgery o o

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Treatment
Have you had persistent chest pain over the last few weeks? Do you feel it could be because of some heart problem? Read on to learn about cardiovascular disease symptoms and their treatment.
By Ashwini Ambekar | Wednesday, October 08, 2008

Cardiovascular Disease Symptoms and

Cardiovascular diseases includes those affecting the heart and its blood vessels. It includes such problems as heart attacks, heart failures, problems of heart valves and heart muscles, strokes and angina. Cardiovascular disease statistics reveal scary figures with this being the leading killer of men and women in the nation. Around 1 million people die every year in America because of cardiovascular diseases. These people belong to different races and ethnic groups. Among all the deaths accounted for in this country, cardiovascular diseases cause 42 percent of these deaths. Contrary to popular belief that old age is a primary factor in cardiovascular diseases, this disease even affects people as young as 35 and older.

Modern stressful lifestyle and the junk food culture are causing even younger people to fall prey to this silent killer. Very few women are aware of the dangers posed by this disease. At the same time as many as 38 percent women experiencing heart attacks die within a year as against 25 percent of men. Also after menopause the number of women developing and dying of cardiovascular diseases is more or less equal to the number of men experiencing the same. Other alarming cardiovascular disease statistics include the fact that by 2015 the number of people dying because of this will reach 20 million. Many times cardiovascular problems are not detected because of absence of pain and other obvious symptoms. In that situation the underlying problems are not treated and this results in even more dangerous health problems such as strokes, heart attacks and even kidney damage. What makes cardiovascular diseases particularly dangerous is the fact that an individual may have multiple conditions at a particular time and may be completely unaware of it. While cardiovascular diseases may exists without any obvious symptoms or pain there are some aspects that can be kept in mind to help identify potential problems. If there is severe interruption in the flow of blood this often results in a heart attack. The symptoms whenever present can be seen in varying degrees depending on the extent to which blood flow is hindered in the organ:

When there is a heart attack there may be pain in the central area of the chest and this pain is extremely oppressive. There can also be an intense squeezing feeling in the chest and this may last up to a few minutes. This chest pain may in some cases last for only a few seconds and in other cases occur sporadically. Sometimes the symptoms include chest pain that spreads around the neck region or shoulder and arm region. There may also be chest discomfort and a feeling of light headedness. Palpitations are another symptom of cardiovascular diseases. Palpitations refer to an unusual degree of awareness regarding the heart beat. Irregular heart beats and skips in heart beats are often experienced as a part of palpitations.

Other cardiovascular disease symptoms include: Sweating Nausea and shortness in breath Vomiting and jaw or back pain Slow healing of cuts and sores Weakness in arms or legs Loss of balance or coordination Difficulty speaking or understanding of speech Severe headache with no known cause Cramps in legs that go away on resting Any loss of feeling in face or body Dizziness Loss of consciousness Swelling in lower extremities (peripheral edema) Extreme shortness in breath, general fatigue and cough particularly after any exercise session or after some activity.

The treatment for cardiovascular diseases depends upon the specific issues pertaining to each case and whether the patient is also suffering from diabetes is important to determine the line of treatment. Initially an electrocardiogram (ECG) is used to determine and record the electrical activity and the rhythm of the heart. Some of the cardiovascular disease treatments include:

ACE inhibitors: ACE inhibitors are called angiotensin converting enzyme inhibitors. This medication helps to widen and dilate the blood vessels so that there is improvement in the amount of blood pumped by the heart and this in turn lowers and regulates the blood pressure. These also increase the blood flow because of which the heart has to work less hard. Beta blockers: These are prescribed to deal with abnormal heart rhythms and since they do not cure arrhythmias these have to be taken for life. Aspirin: Antiplatelets like aspirin is often prescribed for patients suffering from coronary artery disease, stroke, and angina among others. This is used to prevent blood clots from forming in the vessels. Calcium channel blockers: These affect movement of calcium in the cell or blood vessel in the heart. This aids in relaxing the blood vessels, increasing supply of blood to the heart along with oxygen and thereby helps reducing the load on the heart.

Other extensive treatments include: Angioplasty: This procedure is used to open up blood vessels that are blocked. This is done by way of a balloon which is inserted during surgery and inflated inside the blocked vessel to remove the block and thereby open it. Bypass surgery: In bypass surgery a blood vessel from another part of the body is used and this is done to redirect the blood flow around the narrowed or blocked portion of the blood vessel in the heart.

While cardiovascular disease treatment may include medication that a person would need to take for a lifetime or in some cases even extensive surgeries, the most important element is adopting a better lifestyle. This would include quitting smoking and other addictions, eating a well balanced healthy diet with strict control over consumption of excessive oil, junk and sweet food. To recover and maintain good health, exercise in moderate proportions under the guidance of a medical professional is also equally important. Finally adopting a more relaxed and stress free approach towards life is also very important for cardiovascular disease patients.

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Cerebrovascular Disease
I. Intoduction

II. III. IV. V. VI. VII.

Classification of Cerebrovascular Disease Ischemic/Embolic Stroke Treatment of Cerebrovascular Disease Hemorrhagic Stroke (SAH) Case 1 Case 2

Goals and Objectives: 1. List the types of cerebrovascular disease (CVD) and the major causes of each. 2. Discuss the risk factors associated with CVD. 3. Explain the pathophysiology of ischemic and hemorrhagic stroke. 4. Discuss the pharmacologic interventions in CVD. 5. List the goals of therapy in CVD. Required Reading: Bradberry JC. Stroke, in Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds): Pharmacotherapy: A Pathophysiologic Approach. Third Edition. New York, Elsevier, 1997. Chapter 20, pp. 435-458.

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. 2. 3. 4.

hemiplegia (paralysis of one side of the body) hemisensory deficit hemianopsia (blindness in 1/2 of the visual field) 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. b. c. d. e.

CHF 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. b. c. d. e. f.
7. Diabetes Mellitus 8. Migraine HAs 9. Retinal emboli

Age (older) Alcohol abuse Cigarette smoking Drug abuse Genetic factors Males

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. 2. 3. 4.
4. Endovascular procedures a. Balloon Angioplasty

surgical removal of the atheromatous plaque reserved for patients with an ulcerated lesion or clot that occludes > 70% of blood flow in the carotid artery may decrease risk of stroke by 60% over the two years following the procedure vertebral endarterectomy no longer used

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 2. consists of placing a stainless steel coil into the vessel which then sticks to wall of artery
5. Antiplatelet Agents a. Aspirin 1.Mechanism of Action

a. inhibition of platelet aggregation b. decreases release of vasoactive substances from platelets c. irreversible inactivation of platelet cyclooxygenase; effect lasts for the life of the platelet (5-7 days)
2. Efficacy

a. ASA has shown clinically significant reductions (22-24%) in stroke risk and death in randomized trials in patients who have experienced a previous TIA or stroke (secondary
prevention)

b. c. d. e.

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. b. c. d.
2. Efficacy

inhibits ADP-induced platelet aggregation inhibits platelet aggregation induced by collagen, PAF, epinephrine and thrombin bleeding time prolonged minimal effect on cyclooxygenase

a. b. c. d. e.
1. diarrhea 2. rash

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

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. B. C. D.

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. The currently recommended dose of aspirin is 325-975 mg/day. The role of aspirin in the primary prevention of TIAs and stroke is still unclear. 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 b. if consciousness is impaired, suspect a stroke-related seizure, hemorrhage, hypoxia or increased intracranial pressure
2. Supportive care

a. b. c. d. e. f.

Maintain adequate tissue oxygenation: May require airway support and 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. b. c. d. e. f.

isolated neurological deficit 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 b. give 10% of the dose as a bolus over 1-2 minutes and the rest as a continuous infusion over 1 hour c. No antiplatelets or anticoagulants within 24 hours!!
6. Results:

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

severe headache-"the worst headache of my life" 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. b. c. d.

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

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 calcium-induced damage. 3. May dilate penetrating blood vessels allowing blood to be shunted back to 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 has minimal effects on mental status. b. Dose
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 after 3-12 months. d. Phenobarbital and Valproic Acid are alternative agents. Cases - Cerebrovascular disease/Neurosurgery Case 1 A 57yo WM is brought to ER by paramedics. History is unknown, the following medications were found on the patient:
o o o

HCTZ 50mg QD Theophylline SA 300mg Q12 hrs Aldomet 250mg Q12 hrs

o o

ASA w/codeine 60mg ii Q4 hrs prn Cimetidine 400mg QHS

The patient was found unresponsive on the street. The resident has sent off appropriate labs, the vital signs are stable in this unconscious patient. Appropriate labs include: CBC, SMA-7, ABG, U/A, Pt/PTT). 1.What, if any, pharmacologic intervention would you recommend at this time? The goals here are the basic management of the unresponsive patient until specific diagnosis can be established:
o o o o

A-B-Cs (airway-breathing-circulation) - meaning maintain/support basic vital signs and function dextrose 50% 50cc IVP naloxone 0.01mg/kg IVP IV access

Can also include:

o o o

thiamine 100mg theophylline level toxicology screen for other substances which might cause coma

Lab results to date :

140 108 50 5.1 29 3.0

CBC WNL PT 13.7/12 control Based upon physical findings and CT scan, the resident diagnoses cerebrovascular disease. What intervention would you recommend for: 2. Stroke in evolution (also known as progressing stroke)? Maintain A-B-Cs Consider hyperperfusion to maintain cerebral blood flow - this can be accomplished by infusion of hyperosmotic agents to force perfusion through compromised vessels, and example would include mannitol or hemodilution. Once hemorrhage is ruled out, the patient can be started on anticoagulation for thromboembolic stroke - the most rapid onset, and therefore preferred, agent would be heparin infusion. The anticoagulation goal would be PTT 1.5-2 times baseline control. You might hesitate, though since the patient has a prescription vial for cimetidine. Blood pressure should be closely regulated, whether hemorrhagic of thromboembolic stroke. A reasonable goal to maintain cerebral blood flow would be a systolic blood pressure of 130-150. The best agent to select would be one which is rapidly titratable, ie., sodium nitroprusside. Due to the patient's history of hypertension and acute stroke, nimodipine may be a very reasonable selection for acute intervention. The recommended dose acutely is 30mg Q6 hrs. Monitoring parameters and dose limitations for this dihydropyridine compound would include control of blood pressure and prevention of hypotension.

Steroids may be suggested for ischemia-associated cerebral edema, although benefit is questionable. Anticonvulsant prophylaxis is a reasonable consideration. An addition patient-specific concern in this particular patient involves his decreased renal function, and specific attention to drug selection and monitoring parameters. 3. Completed Stroke? Maintain A-B-Cs Maintain CBF (cerebral blood flow) Blood pressure regulation Theophylline and cimetidine assessment Hyperperfusion once the stroke is completed is probably not beneficial. Occasionally clinicians will recommend hyperperfusion in selected very compromised patients, with the hope that this hyperperfusion will enhance formation of collateral circulation. This is very risky and should not be routinely recommended. Antiplatelet therapy longer term for preventing further cerebrovascular problems is probably a good choice. Need to consider anticonvulsants and steroids. Over the next 24 hours the patient's symptoms resolve completely. The prevailing diagnosis is TIA. 4. Discuss medical intervention in this patient, include advantages and disadvantages. Control blood pressure AnticoagulationBeneficial for new onset TIAs Acutely with heparin/overlap with warfarin therapy change over to antiplatelet agents after 12 months Consider cimetidine prescription in this patient ? history of PUD, assess bleeding risk in patient with already mildly elevated PT, increase in BUN prior to treatment Consider patient education concerns and drug interaction. Antiplatelet agents-

May be beneficial longer term with less risk of bleeding. If symptoms of progressing disease, antiplatelet agents are probably not useful anticoagulation or surgical intervention may be indicated. Neurology consultation differs with the resident - Neurology diagnoses cerebral edema secondary to tumor. The patient is then transferred to the Neurology Service. The patient deteriorates with signs of severely increased ICP. 5. Discuss the various modes of intervention for acute severe increased ICP in this unconscious patient. A-B-Cs Fluid restriction 1/2 to 2/3 maintenance. Elevate head of the bed 30 degrees Consider loop diuretic first, should be cautious about osmotic agents, due to decreased renal function. Steroids dexamethasone 10mg IV Q6 hrs Hyperventilation is fastest intervention to pCO2 24-28 May additionally consider: Removal of CSF - via lumbar puncture/tap or shunt barbiturate coma surgical decompression of tumor is probably best, although drug therapy interventions would buy time to prepare the patient for emergent surgery. Case 2. A 57yo WM is brought to the ER by paramedics who found him in an alley - a victim of blunt trauma to his head and body. Past medical history is not available. The following medications were found on the patient:
o o o o

HCTZ 50mg QAM Digoxin 0.125mg QAM NTG 0.4mg SL prn chest pain Mylanta II ii tabs PO Q4 hrs prn

Pertinent PE: WDWN male responsive only to deep pain bp 220/110 HR 105 RR 8 T 97.8 HEENT:

o o o o

depressed skull fracture and multiple lacerations R pupil non-reactive, bilateral papilledema stiff neck bilateral carotid bruits

cor S1 S2 S3, no S4, ? mitral stenosis 1. CT scan reveals diffuse cerebral edema and no evidence of hematoma at this time. The physician asks you for recommendations to manage this patient's problem - be specific (drug, dose, monitoring parameters). Make sure that basic A-B-Cs are maintained in this patient with complex medical history (from medications) Management of cerebral edema: a. Non-pharmacologic bedrest head of bed elevated 30 degrees if intubated for ventilatory support (RR 8), use hyperventilation to pCO2 24-28 b. Pharmacologic fluid restriction to 2/3 to 3/4 maintenance fluids mannitol 0.25 - 0.5 gm/kg Q4 hrs IVPB using 20% solution monitoring parameters:
o o o o

fluid balance I/O serum and urine osmolality electrolytes, esp Na, K renal function and urine output

additional considerations:
o o o

anticonvulsant prophylaxis for post-traumatic seizures evaluate for other signs of trauma antibiotics for open wound - need to cover skin flora, tetanus

2. Day 3 in the hospital, the patient develops R sided hemiparesis of upper and lower extremities. What are the risk factors for cerebrovascular disease in this patient? Risk factors include possibly history of

o o o

hypertension mitral stenosis traumatic injury in patient with carotid bruits

3. How would you manage this patient's completed stroke? Poor candidate for anticoagulation with recent trauma, and history of antacid use (consider potential GI bleed). Best alternative to help prevent further stroke injury would be aspirin. This patient should probably be treated since he has bilateral carotid bruits, and other risk factors.
http://www.uic.edu/classes/pmpr/pmpr652/Final/Winkler/CVD.html

http://www.imarksweb.net/book/cvd+pathophysiology+diagram/