stroke - wikipedia, the free encyclopedia

StrokeClassification and external resources

CT scan slice of the brain showing a right-hemispheric ischemic stroke (left side of image).

ICD-10 I61. (http://apps.who.int/classifications/apps/icd/icd10online/?gi60.htm+i61) -I64.(http://apps.who.int/classifications/apps/icd/icd10online/?gi60.htm+i64)

ICD-9 434.91 (http://www.icd9data.com/getICD9Code.ashx?icd9=434.91)

OMIM 601367(http://www.ncbi.nlm.nih.gov/omim/601367)

DiseasesDB 2247(http://www.diseasesdatabase.com/ddb2247.htm)

MedlinePlus 000726 (http://www.nlm.nih.gov/medlineplus/ency/article/000726.htm)

eMedicine neuro/9 (http://www.emedicine.com/neuro/topic9.htm) emerg/558(http://www.emedicine.com/emerg/topic558.htm#) emerg/557

StrokeFrom Wikipedia, the free encyclopedia

A stroke, previously known medically as acerebrovascular accident (CVA), is therapidly developing loss of brain function(s)due to disturbance in the blood supply to thebrain. This can be due to ischemia (lack ofblood flow) caused by blockage(thrombosis, arterial embolism), or ahemorrhage (leakage of blood).[1] As aresult, the affected area of the brain isunable to function, leading to inability tomove one or more limbs on one side of thebody, inability to understand or formulatespeech, or an inability to see one side of thevisual field.[2]

A stroke is a medical emergency and cancause permanent neurological damage,complications, and lead to death. It is theleading cause of adult disability in theUnited States and Europe and it is thesecond leading cause of death worldwide.[3]Risk factors for stroke include advancedage, hypertension (high blood pressure),previous stroke or transient ischemic attack(TIA), diabetes, high cholesterol, cigarettesmoking and atrial fibrillation.[2] Highblood pressure is the most importantmodifiable risk factor of stroke.[2]

An ischemic stroke is occasionally treated ina hospital with thrombolysis (also known asa "clot buster"), and some hemorrhagicstrokes benefit from neurosurgery.Treatment to recover any lost function istermed stroke rehabilitation, ideally in astroke unit and involving health professionssuch as speech and language therapy,physical therapy and occupational therapy.Prevention of recurrence may involve theadministration of antiplatelet drugs such asaspirin and dipyridamole, control andreduction of hypertension, and the use of

Stroke - Wikipedia, the free encyclopedia http://en.wikipedia.org/w/index.php?title=Stroke&printable=yes

1 of 31 13/03/11 10:42 PM

(http://www.emedicine.com/emerg/topic557.htm#) pmr/187(http://www.emedicine.com/pmr/topic187.htm#)

MeSH D020521 (http://www.nlm.nih.gov/cgi/mesh/2010/MB_cgi?field=uid&term=D020521)

statins. Selected patients may benefit fromcarotid endarterectomy and the use ofanticoagulants.[2]

Contents1 Definition2 Classification

2.1 Ischemic2.2 Hemorrhagic

3 Signs and symptoms3.1 Early recognition3.2 Subtypes3.3 Associated symptoms

4 Causes5 Pathophysiology

5.1 Ischemic5.2 Hemorrhagic

6 Diagnosis6.1 Physical examination6.2 Imaging6.3 Underlying etiology

7 Prevention7.1 Risk factors

7.1.1 Blood pressure7.1.2 Atrial fibrillation7.1.3 Blood lipids7.1.4 Diabetes mellitus7.1.5 Anticoagulationdrugs7.1.6 Surgery7.1.7 Nutritional andmetabolic interventions

8 Treatment8.1 Stroke unit8.2 Treatment of ischemicstroke

8.2.1 Thrombolysis8.2.2 Mechanicalthrombectomy8.2.3 Angioplasty andstenting

8.3 Secondary prevention ofischemic stroke


2 of 31 13/03/11 10:42 PM

A slice of brain from theautopsy of a person whosuffered an acute middlecerebral artery (MCA) stroke

8.4 Treatment of hemorrhagicstroke

9 Care and rehabilitation10 Prognosis11 Epidemiology12 History13 External Links14 References15 Further reading

Definition

The traditional definition of stroke , devised by the World Health Organization in the 1970s,[4]is a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or isinterrupted by death within 24 hours". This definition was supposed to reflect the reversibilityof tissue damage and was devised for the purpose, with the time frame of 24 hours beingchosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack, which is arelated syndrome of stroke symptoms that resolve completely within 24 hours.[2] With theavailability of treatments that, when given early, can reduce stroke severity, many now preferalternative concepts, such as brain attack and acute ischemic cerebrovascular syndrome(modeled after heart attack and acute coronary syndrome respectively), that reflect the urgencyof stroke symptoms and the need to act swiftly.[5]

ClassificationStrokes can be classified into two major categories: ischemicand hemorrhagic.[6] Ischemic strokes are those that are causedby interruption of the blood supply, while hemorrhagic strokesare the ones which result from rupture of a blood vessel or anabnormal vascular structure. About 87% of strokes are causedby ischemia, and the remainder by hemorrhage. Somehemorrhages develop inside areas of ischemia ("hemorrhagictransformation"). It is unknown how many hemorrhagesactually start as ischemic stroke.[2]

Ischemic

Main articles: Cerebral infarction and Brain ischemia

In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction ofthe brain tissue in that area. There are four reasons why this might happen:

Thrombosis (obstruction of a blood vessel by a blood clot forming locally)1.


3 of 31 13/03/11 10:42 PM

CT scan showing anintracerebral hemorrhagewith associatedintraventricularhemorrhage.

Embolism (obstruction due to an embolus from elsewhere in the body, see below),[2]2.Systemic hypoperfusion (general decrease in blood supply, e.g. in shock)[7]3.Venous thrombosis.[8]4.

Stroke without an obvious explanation is termed "cryptogenic" (of unknown origin); thisconstitutes 30-40% of all ischemic strokes.[2][9]

There are various classification systems for acute ischemic stroke. The Oxford CommunityStroke Project classification (OCSP, also known as the Bamford or Oxford classification) reliesprimarily on the initial symptoms; based on the extent of the symptoms, the stroke episode isclassified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI),lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict theextent of the stroke, the area of the brain affected, the underlying cause, and the prognosis.[10][11] The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based onclinical symptoms as well as results of further investigations; on this basis, a stroke is classifiedas being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2)embolism of cardiac origin, (3) occlusion of a small blood vessel, (4) other determined cause,(5) undetermined cause (two possible causes, no cause identified, or incomplete investigation).[2][12]

Hemorrhagic

Main articles: Intracranial hemorrhage and intracerebral hemorrhage

Intracranial hemorrhage is the accumulation of blood anywherewithin the skull vault. A distinction is made between intra-axialhemorrhage (blood inside the brain) and extra-axial hemorrhage(blood inside the skull but outside the brain). Intra-axialhemorrhage is due to intraparenchymal hemorrhage orintraventricular hemorrhage (blood in the ventricular system).The main types of extra-axial hemorrhage are epiduralhematoma (bleeding between the dura mater and the skull),subdural hematoma (in the subdural space) and subarachnoidhemorrhage (between the arachnoid mater and pia mater). Mostof the hemorrhagic stroke syndromes have specific symptoms(e.g. headache, previous head injury).

Signs and symptomsStroke symptoms typically start suddenly, over seconds tominutes, and in most cases do not progress further. Thesymptoms depend on the area of the brain affected. The more extensive the area of brainaffected, the more functions that are likely to be lost. Some forms of stroke can causeadditional symptoms. For example, in intracranial hemorrhage, the affected area may compressother structures. Most forms of stroke are not associated with headache, apart from


4 of 31 13/03/11 10:42 PM

subarachnoid hemorrhage and cerebral venous thrombosis and occasionally intracerebralhemorrhage.

Early recognition

Various systems have been proposed to increase recognition of stroke by patients, relatives andemergency first responders. A systematic review, updating a previous systematic review from1994, looked at a number of trials to evaluate how well different physical examination findingsare able to predict the presence or absence of stroke. It was found that sudden-onset faceweakness, arm drift (e.g. if a person, when asked to raise both arms, involuntarily lets one armdrift downward) and abnormal speech are the findings most likely to lead to the correctidentification of a case of stroke (+ likelihood ratio of 5.5 when at least one of these is present).Similarly, when all three of these are absent, the likelihood of stroke is significantly decreased(– likelihood ratio of 0.39).[13] While these findings are not perfect for diagnosing stroke, thefact that they can be evaluated relatively rapidly and easily make them very valuable in theacute setting.

Proposed systems include FAST (stroke) (face, arm, speech, and time),[14] as advocated by theDepartment of Health (United Kingdom) and The Stroke Association, the American StrokeAssociation (www.strokeassociation.org) , National Stroke Association (US www.stroke.org),the Los Angeles Prehospital Stroke Screen (LAPSS)[15] and the Cincinnati Prehospital StrokeScale (CPSS).[16] Use of these scales is recommended by professional guidelines.[17]

For people referred to the emergency room, early recognition of stroke is deemed important asthis can expedite diagnostic tests and treatments. A scoring system called ROSIER (recognitionof stroke in the emergency room) is recommended for this purpose; it is based on features fromthe medical history and physical examination.[17][18]

Subtypes

If the area of the brain affected contains one of the three prominent central nervous systempathways—the spinothalamic tract, corticospinal tract, and dorsal column (medial lemniscus),symptoms may include:

hemiplegia and muscle weakness of the facenumbnessreduction in sensory or vibratory sensation

In most cases, the symptoms affect only one side of the body (unilateral). Depending on thepart of the brain affected, the defect in the brain is usually on the opposite side of the body.However, since these pathways also travel in the spinal cord and any lesion there can alsoproduce these symptoms, the presence of any one of these symptoms does not necessarilyindicate a stroke.

In addition to the above CNS pathways, the brainstem also consists of the 12 cranial nerves. Astroke affecting the brain stem therefore can produce symptoms relating to deficits in these


5 of 31 13/03/11 10:42 PM

cranial nerves:

altered smell, taste, hearing, or vision (total or partial)drooping of eyelid (ptosis) and weakness of ocular musclesdecreased reflexes: gag, swallow, pupil reactivity to lightdecreased sensation and muscle weakness of the facebalance problems and nystagmusaltered breathing and heart rateweakness in sternocleidomastoid muscle with inability to turn head to one sideweakness in tongue (inability to protrude and/or move from side to side)

If the cerebral cortex is involved, the CNS pathways can again be affected, but also canproduce the following symptoms:

aphasia (difficulty with verbal expression, auditory comprehension, reading and/orwriting Broca's or Wernicke's area typically involved)dysarthria (motor speech disorder resulting from neurological injury)apraxia (altered voluntary movements)visual field defectmemory deficits (involvement of temporal lobe)hemineglect (involvement of parietal lobe)disorganized thinking, confusion, hypersexual gestures (with involvement of frontallobe)anosognosia (persistent denial of the existence of a, usually stroke-related, deficit)

If the cerebellum is involved, the patient may have the following:

trouble walkingaltered movement coordinationvertigo and or disequilibrium

Associated symptoms

Loss of consciousness, headache, and vomiting usually occurs more often in hemorrhagicstroke than in thrombosis because of the increased intracranial pressure from the leaking bloodcompressing the brain.

If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage oran embolic stroke.

CausesThrombotic stroke

In thrombotic stroke a thrombus (blood clot) usually forms around atherosclerotic plaques.Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. Athrombus itself (even if non-occluding) can lead to an embolic stroke (see below) if thethrombus breaks off, at which point it is called an "embolus." Two types of thrombosis cancause stroke:


6 of 31 13/03/11 10:42 PM

Large vessel disease involves the common and internal carotids, vertebral, and the Circleof Willis. Diseases that may form thrombi in the large vessels include (in descendingincidence): atherosclerosis, vasoconstriction (tightening of the artery), aortic, carotid orvertebral artery dissection, various inflammatory diseases of the blood vessel wall(Takayasu arteritis, giant cell arteritis, vasculitis), noninflammatory vasculopathy,Moyamoya disease and fibromuscular dysplasia.Small vessel disease involves the smaller arteries inside the brain: branches of the circleof Willis, middle cerebral artery, stem, and arteries arising from the distal vertebral andbasilar artery. Diseases that may form thrombi in the small vessels include (in descendingincidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as a resultof high blood pressure and aging) and fibrinoid degeneration (stroke involving thesevessels are known as lacunar infarcts) and microatheroma (small atheroscleroticplaques).

Sickle cell anemia, which can cause blood cells to clump up and block blood vessels, can alsolead to stroke. A stroke is the second leading killer of people under 20 who suffer fromsickle-cell anemia.[19]

Embolic stroke

An embolic stroke refers to the blockage of an artery by an arterial embolus, a travellingparticle or debris in the arterial bloodstream originating from elsewhere. An embolus is mostfrequently a thrombus, but it can also be a number of other substances including fat (e.g. frombone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectiousendocarditis).

Because an embolus arises from elsewhere, local therapy solves the problem only temporarily.Thus, the source of the embolus must be identified. Because the embolic blockage is sudden inonset, symptoms usually are maximal at start. Also, symptoms may be transient as the embolusis partially resorbed and moves to a different location or dissipates altogether.

Emboli most commonly arise from the heart (especially in atrial fibrillation) but may originatefrom elsewhere in the arterial tree. In paradoxical embolism, a deep vein thrombosis embolisesthrough an atrial or ventricular septal defect in the heart into the brain.

Cardiac causes can be distinguished between high and low-risk:[20]

High risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of themitral or aortic valve disease, artificial heart valves, known cardiac thrombus of theatrium or ventricle, sick sinus syndrome, sustained atrial flutter, recent myocardialinfarction, chronic myocardial infarction together with ejection fraction <28 percent,symptomatic congestive heart failure with ejection fraction <30 percent, dilatedcardiomyopathy, Libman-Sacks endocarditis, Marantic endocarditis, infectiveendocarditis, papillary fibroelastoma, left atrial myxoma and coronary artery bypass graft(CABG) surgeryLow risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramenovale (PFO), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale,left ventricular aneurysm without thrombus, isolated left atrial "smoke" onechocardiography (no mitral stenosis or atrial fibrillation), complex atheroma in the


7 of 31 13/03/11 10:42 PM

ascending aorta or proximal arch

Systemic hypoperfusion

Systemic hypoperfusion is the reduction of blood flow to all parts of the body. It is mostcommonly due to cardiac pump failure from cardiac arrest or arrhythmias, or from reducedcardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion,or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion.Because the reduction in blood flow is global, all parts of the brain may be affected, especially"watershed" areas - border zone regions supplied by the major cerebral arteries. A watershedstroke refers to the condition when blood supply to these areas is compromised. Blood flow tothese areas does not necessarily stop, but instead it may lessen to the point where brain damagecan occur. This phenomenon is also referred to as "last meadow" to point to the fact that inirrigation the last meadow receives the least amount of water.

Venous thrombosis

Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure,which exceeds the pressure generated by the arteries. Infarcts are more likely to undergohemorrhagic transformation (leaking of blood into the damaged area) than other types ofischemic stroke.[8]

Intracerebral hemorrhage

It generally occurs in small arteries or arterioles and is commonly due to hypertension,intracranial vascular malformations (including cavernous angiomas or arteriovenousmalformations), cerebral amyloid angiopathy, or infarcts into which secondary haemorrhagehas occurred.[2] Other potential causes are trauma, bleeding disorders, amyloid angiopathy,illicit drug use (e.g. amphetamines or cocaine). The hematoma enlarges until pressure fromsurrounding tissue limits its growth, or until it decompresses by emptying into the ventricularsystem, CSF or the pial surface. A third of intracerebral bleed is into the brain's ventricles. ICHhas a mortality rate of 44 percent after 30 days, higher than ischemic stroke or even the verydeadly subarachnoid hemorrhage (which, however, also may be classified as a type ofstroke[2]).

PathophysiologyIschemic


8 of 31 13/03/11 10:42 PM

Micrograph showing corticalpseudolaminar necrosis, afinding seen in strokes onmedical imaging and at autopsy.H&E-LFB stain.

Micrograph of the superficialcerebral cortex showing neuronloss and reactive astrocytes in aperson that suffered a stroke.H&E-LFB stain.

Ischemic stroke occurs due to a loss of blood supply to partof the brain, initiating the ischemic cascade.[21] Brain tissueceases to function if deprived of oxygen for more than 60 to90 seconds and after approximately three hours, will sufferirreversible injury possibly leading to death of the tissue,i.e., infarction. (This is why TPA's (e.g. Streptokinase,Altapase) are given only until three hours since the onset ofthe stroke.) Atherosclerosis may disrupt the blood supply bynarrowing the lumen of blood vessels leading to a reductionof blood flow, by causing the formation of blood clots withinthe vessel, or by releasing showers of small emboli throughthe disintegration of atherosclerotic plaques. Embolicinfarction occurs when emboli formed elsewhere in thecirculatory system, typically in the heart as a consequence ofatrial fibrillation, or in the carotid arteries, break off, enterthe cerebral circulation, then lodge in and occlude brainblood vessels. Since blood vessels in the brain are nowoccluded, the brain becomes low in energy, and thus itresorts into using anaerobic respiration within the region ofbrain tissue affected by ischemia. Unfortunately, this kind ofrespiration produces less adenosine triphosphate (ATP) butreleases a by-product called lactic acid. Lactic acid is anirritant which could potentially destroy cells since it is anacid and disrupts the normal acid-base balance in the brain.The ischemia area is referred to as the "ischemicpenumbra".[22]

Then, as oxygen or glucose becomes depleted in ischemicbrain tissue, the production of high energy phosphatecompounds such as adenosine triphosphate (ATP) fails,leading to failure of energy-dependent processes (such as ionpumping) necessary for tissue cell survival. This sets off aseries of interrelated events that result in cellular injury anddeath. A major cause of neuronal injury is release of theexcitatory neurotransmitter glutamate. The concentration ofglutamate outside the cells of the nervous system is normallykept low by so-called uptake carriers, which are powered by the concentration gradients of ions(mainly Na+) across the cell membrane. However, stroke cuts off the supply of oxygen andglucose which powers the ion pumps maintaining these gradients. As a result thetransmembrane ion gradients run down, and glutamate transporters reverse their direction,releasing glutamate into the extracellular space. Glutamate acts on receptors in nerve cells(especially NMDA receptors), producing an influx of calcium which activates enzymes thatdigest the cells' proteins, lipids and nuclear material. Calcium influx can also lead to the failureof mitochondria, which can lead further toward energy depletion and may trigger cell death dueto apoptosis.


9 of 31 13/03/11 10:42 PM

Ischemia also induces production of oxygen free radicals and other reactive oxygen species.These react with and damage a number of cellular and extracellular elements. Damage to theblood vessel lining or endothelium is particularly important. In fact, many antioxidantneuroprotectants such as uric acid and NXY-059 work at the level of the endothelium and notin the brain per se. Free radicals also directly initiate elements of the apoptosis cascade bymeans of redox signaling.[19]

These processes are the same for any type of ischemic tissue and are referred to collectively asthe ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it haslittle respiratory reserve and is completely dependent on aerobic metabolism, unlike most otherorgans.

Brain tissue survival can be improved to some extent if one or more of these processes isinhibited. Drugs that scavenge reactive oxygen species, inhibit apoptosis, or inhibit excitatoryneurotransmitters, for example, have been shown experimentally to reduce tissue injury due toischemia. Agents that work in this way are referred to as being neuroprotective. Until recently,human clinical trials with neuroprotective agents have failed, with the probable exception ofdeep barbiturate coma. However, more recently NXY-059, the disulfonyl derivative of theradical-scavenging spintrap phenylbutylnitrone, is reported to be neuroprotective in stroke.[23]This agent appears to work at the level of the blood vessel lining or endothelium.Unfortunately, after producing favorable results in one large-scale clinical trial, a second trialfailed to show favorable results.[19]

In addition to injurious effects on brain cells, ischemia and infarction can result in loss ofstructural integrity of brain tissue and blood vessels, partly through the release of matrixmetalloproteases, which are zinc- and calcium-dependent enzymes that break down collagen,hyaluronic acid, and other elements of connective tissue. Other proteases also contribute to thisprocess. The loss of vascular structural integrity results in a breakdown of the protective bloodbrain barrier that contributes to cerebral edema, which can cause secondary progression of thebrain injury.

As is the case with any type of brain injury, the immune system is activated by cerebralinfarction and may under some circumstances exacerbate the injury caused by the infarction.Inhibition of the inflammatory response has been shown experimentally to reduce tissue injurydue to cerebral infarction, but this has not proved out in clinical studies.

Hemorrhagic


10 of 31 13/03/11 10:42 PM

Head CT showing deepintracerebral hemorrhage due tobleeding within the cerebellum,approximately 30 hours old.

Hemorrhagic strokes result in tissue injury by causingcompression of tissue from an expanding hematoma orhematomas. This can distort and injure tissue. In addition,the pressure may lead to a loss of blood supply to affectedtissue with resulting infarction, and the blood released bybrain hemorrhage appears to have direct toxic effects onbrain tissue and vasculature.[19]

DiagnosisStroke is diagnosed through several techniques: aneurological examination (such as the Nihss), CT scans(most often without contrast enhancements) or MRIscans, Doppler ultrasound, and arteriography. Thediagnosis of stroke itself is clinical, with assistance fromthe imaging techniques. Imaging techniques also assist indetermining the subtypes and cause of stroke. There is yetno commonly used blood test for the stroke diagnosis itself, though blood tests may be of helpin finding out the likely cause of stroke.[24]

Physical examination

A physical examination, including taking a medical history of the symptoms and a neurologicalstatus, helps giving an evaluation of the location and severity of a stroke. It can give a standardscore on e.g. the NIH stroke scale.

Imaging

For diagnosing ischemic stroke in the emergency setting:[25]

CT scans (without contrast enhancements)

sensitivity= 16%specificity= 96%

MRI scan


For diagnosing hemorrhagic stroke in the emergency setting:

CT scans (without contrast enhancements)



11 of 31 13/03/11 10:42 PM

MRI scan


For detecting chronic hemorrhages, MRI scan is more sensitive.[26]

For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may behelpful. SPECT documents cerebral blood flow and PET with FDG isotope the metabolicactivity of the neurons.

Underlying etiology

When a stroke has been diagnosed, various other studies may be performed to determine theunderlying etiology. With the current treatment and diagnosis options available, it is ofparticular importance to determine whether there is a peripheral source of emboli. Testselection may vary, since the cause of stroke varies with age, comorbidity and the clinicalpresentation. Commonly used techniques include:

an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis) ordissection of the precerebral arteriesan electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultantclots in the heart which may spread to the brain vessels through the bloodstream)a Holter monitor study to identify intermittent arrhythmiasan angiogram of the cerebral vasculature (if a bleed is thought to have originated from ananeurysm or arteriovenous malformation)blood tests to determine hypercholesterolemia, bleeding diathesis and some rarer causessuch as homocysteinuria

Prevention

Given the disease burden of strokes, prevention is an important public health concern.[27]Primary prevention is less effective than secondary prevention (as judged by the numberneeded to treat to prevent one stroke per year).[27] Recent guidelines detail the evidence forprimary prevention in stroke.[28] Because stroke may indicate underlying atherosclerosis, it isimportant to determine the patient's risk for other cardiovascular diseases such as coronaryheart disease. Conversely, aspirin prevents against first stroke in patients who have suffered amyocardial infarction or patients with a high cardiovascular risk.[29][30]

Risk factors

The most important modifiable risk factors for stroke are high blood pressure and atrialfibrillation (although magnitude of this effect is small: the evidence from the Medical ResearchCouncil trials is that 833 patients have to be treated for 1 year to prevent one stroke[31][32]).Other modifiable risk factors include high blood cholesterol levels, diabetes, cigarettesmoking[33][34] (active and passive), heavy alcohol consumption[35] and drug use,[36] lack of


12 of 31 13/03/11 10:42 PM

physical activity, obesity and unhealthy diet.[37] Alcohol use could predispose to ischemicstroke, and intracerebral and subarachnoid hemorrhage via multiple mechanisms (for examplevia hypertension, atrial fibrillation, rebound thrombocytosis and platelet aggregation andclotting disturbances).[38] The drugs most commonly associated with stroke are cocaine,amphetamines causing hemorrhagic stroke, but also over-the-counter cough and cold drugscontaining sympathomimetics.[39][40]

No high quality studies have shown the effectiveness of interventions aimed at weightreduction, promotion of regular exercise, reducing alcohol consumption or smokingcessation.[41] Nonetheless, given the large body of circumstantial evidence, best medicalmanagement for stroke includes advice on diet, exercise, smoking and alcohol use.[42]Medication or drug therapy is the most common method of stroke prevention; carotidendarterectomy can be a useful surgical method of preventing stroke.

Blood pressure

Hypertension accounts for 35-50% of stroke risk.[43] Epidemiological studies suggest thateven a small blood pressure reduction (5 to 6 mmHg systolic, 2 to 3 mmHg diastolic) wouldresult in 40% fewer strokes.[44] Lowering blood pressure has been conclusively shown toprevent both ischemic and hemorrhagic strokes.[45][46] It is equally important in secondaryprevention.[47] Even patients older than 80 years and those with isolated systolic hypertensionbenefit from antihypertensive therapy.[48][49][50] Studies show that intensive antihypertensivetherapy results in a greater risk reduction.[51] The available evidence does not show largedifferences in stroke prevention between antihypertensive drugs —therefore, other factors suchas protection against other forms of cardiovascular disease should be considered andcost.[51][52]

Atrial fibrillation

Patients with atrial fibrillation have a risk of 5% each year to develop stroke, and this risk iseven higher in those with valvular atrial fibrillation.[53] Depending on the stroke risk,anticoagulation with medications such as coumarins or aspirin is warranted for strokeprevention.[54]

Blood lipids

High cholesterol levels have been inconsistently associated with (ischemic) stroke.[46][55]

Statins have been shown to reduce the risk of stroke by about 15%.[56] Since earliermeta-analyses of other lipid-lowering drugs did not show a decreased risk,[57] statins mightexert their effect through mechanisms other than their lipid-lowering effects.[56]


13 of 31 13/03/11 10:42 PM

Diabetes mellitus

Patients with diabetes mellitus are 2 to 3 times more likely to develop stroke, and theycommonly have hypertension and hyperlipidemia. Intensive disease control has been shown toreduce microvascular complications such as nephropathy and retinopathy but notmacrovascular complications such as stroke.[58][59]

Anticoagulation drugs

Oral anticoagulants such as warfarin have been the mainstay of stroke prevention for over 50years. However, several studies have shown that aspirin and antiplatelet drugs are highlyeffective in secondary prevention after a stroke or transient ischemic attack.[29] Low doses ofaspirin (for example 75–150 mg) are as effective as high doses but have fewer side effects; thelowest effective dose remains unknown.[60] Thienopyridines (clopidogrel, ticlopidine) "mightbe slightly more effective" than aspirin and have a decreased risk of gastrointestinal bleeding,but they are more expensive.[61] Their exact role remains controversial. Ticlopidine has moreskin rash, diarrhea, neutropenia and thrombotic thrombocytopenic purpura.[61] Dipyridamolecan be added to aspirin therapy to provide a small additional benefit, even though headache is acommon side effect.[62] Low-dose aspirin is also effective for stroke prevention aftersustaining a myocardial infarction.[30] Except for in atrial fibrillation, oral anticoagulants arenot advised for stroke prevention —any benefit is offset by bleeding risk.[63]

In primary prevention however, antiplatelet drugs did not reduce the risk of ischemic strokewhile increasing the risk of major bleeding.[64][65] Further studies are needed to investigate apossible protective effect of aspirin against ischemic stroke in women.[66][67]

Surgery

Surgical procedures such as carotid endarterectomy or carotid angioplasty can be used toremove significant atherosclerotic narrowing (stenosis) of the carotid artery, which suppliesblood to the brain. There is a large body of evidence supporting this procedure in selectedcases.[42] Endarterectomy for a significant stenosis has been shown to be useful in thesecondary prevention after a previous symptomatic stroke.[68] Carotid artery stenting has notbeen shown to be equally useful.[69][70] Patients are selected for surgery based on age, gender,degree of stenosis, time since symptoms and patients' preferences.[42] Surgery is most efficientwhen not delayed too long —the risk of recurrent stroke in a patient who has a 50% or greaterstenosis is up to 20% after 5 years, but endarterectomy reduces this risk to around 5%. Thenumber of procedures needed to cure one patient was 5 for early surgery (within two weeksafter the initial stroke), but 125 if delayed longer than 12 weeks.[71][72]

Screening for carotid artery narrowing has not been shown to be a useful screening test in thegeneral population.[73] Studies of surgical intervention for carotid artery stenosis without


14 of 31 13/03/11 10:42 PM

symptoms have shown only a small decrease in the risk of stroke.[74][75] To be beneficial, thecomplication rate of the surgery should be kept below 4%. Even then, for 100 surgeries, 5patients will benefit by avoiding stroke, 3 will develop stroke despite surgery, 3 will developstroke or die due to the surgery itself, and 89 will remain stroke-free but would also have doneso without intervention.[42]

Nutritional and metabolic interventions

Nutrition, specifically the Mediterranean-style diet, has the potential of more than halvingstroke risk.[76]

With regards to lowering homocysteine, a meta-analysis of previous trials has concluded thatlowering homocysteine with folic acid and other supplements may reduce stroke risk.[77]However, the two largest randomized controlled trials included in the meta-analysis hadconflicting results. One reported positive results;[78] whereas the other was negative.[79]

The European Society of Cardiology and the European Association for CardiovascularPrevention and Rehabilitation have developed an interactive tool for prediction and managingthe risk of heart attack and stroke in Europe. HeartScore is aimed at supporting clinicians inoptimising individual cardiovascular risk reduction. The Heartscore Programme is available in12 languages and offers web based or PC version.[80]

TreatmentStroke unit

Ideally, people who have had a stroke are admitted to a "stroke unit", a ward or dedicated areain hospital staffed by nurses and therapists with experience in stroke treatment. It has beenshown that people admitted to a stroke unit have a higher chance of surviving than thoseadmitted elsewhere in hospital, even if they are being cared for by doctors without experiencein stroke.[2]

When an acute stroke is suspected by history and physical examination, the goal of earlyassessment is to determine the cause. Treatment varies according to the underlying cause of thestroke, thromboembolic (ischemic) or hemorrhagic. A non-contrast head CT scan can rapidlyidentify a hemorrhagic stroke by imaging bleeding in or around the brain. If no bleeding isseen, a presumptive diagnosis of ischemic stroke is made.

Treatment of ischemic stroke

An ischemic stroke is caused by a thrombus (blood clot) occluding blood flow to an arterysupplying the brain. Definitive therapy is aimed at removing the blockage by breaking the clotdown (thrombolysis), or by removing it mechanically (thrombectomy). The more rapidly bloodflow is restored to the brain, the fewer brain cells die.[81]


15 of 31 13/03/11 10:42 PM

Other medical therapies are aimed at minimizing clot enlargement or preventing new clotsfrom forming. To this end, treatment with medications such as aspirin, clopidogrel anddipyridamole may be given to prevent platelets from aggregating.[29]

In addition to definitive therapies, management of acute stroke includes control of bloodsugars, ensuring the patient has adequate oxygenation and adequate intravenous fluids. Patientsmay be positioned with their heads flat on the stretcher, rather than sitting up, to increase bloodflow to the brain. It is common for the blood pressure to be elevated immediately following astroke. Although high blood pressure may cause some strokes, hypertension during acutestroke is desirable to allow adequate blood flow to the brain.

Thrombolysis

In increasing numbers of primary stroke centers, pharmacologic thrombolysis ("clot busting")with the drug tissue plasminogen activator (tPA), is used to dissolve the clot and unblock theartery. However, the use of tPA in acute stroke is controversial. On one hand, it is endorsed bythe American Heart Association and the American Academy of Neurology as therecommended treatment for acute stroke within three hours of onset of symptoms as long asthere are not other contraindications (such as abnormal lab values, high blood pressure, orrecent surgery). This position for tPA is based upon the findings of two studies by one group ofinvestigators[82] which showed that tPA improves the chances for a good neurologicaloutcome. When administered within the first three hours, 39% of all patients who were treatedwith tPA had a good outcome at three months, only 26% of placebo controlled patients had agood functional outcome. A recent study using alteplase for thrombolysis in ischemic strokesuggests clinical benefit with administration 3 to 4.5 hours after stroke onset.[83] However, inthe NINDS trial 6.4% of patients with large strokes developed substantial brain hemorrhage asa complication from being given tPA. A recent study found the mortality to be higher amongpatients receiving tPA versus those who did not.[84] Additionally, it is the position of theAmerican Academy of Emergency Medicine that objective evidence regarding the efficacy,safety, and applicability of tPA for acute ischemic stroke is insufficient to warrant itsclassification as standard of care.[85]

Intra-arterial fibrinolysis, where a catherter is passed up an artery into the brain and themedication is injected at the site of thrombosis, has been found to improve outcomes in peoplewith acute ischemic stroke.[86]

Mechanical thrombectomy


16 of 31 13/03/11 10:42 PM

Merci Retriever L5.

Another intervention for acute ischemic stroke is removal of theoffending thrombus directly. This is accomplished by inserting acatheter into the femoral artery, directing it into the cerebralcirculation, and deploying a corkscrew-like device to ensnare theclot, which is then withdrawn from the body. Mechanicalembolectomy devices have been demonstrated effective at restoringblood flow in patients who were unable to receive thrombolyticdrugs or for whom the drugs were ineffective,[87][88][89][90] thoughno differences have been found between newer and older versionsof the devices.[91] The devices have only been tested on patientstreated with mechanical clot embolectomy within eight hours of theonset of symptoms.

Angioplasty and stenting

Angioplasty and stenting have begun to be looked at as possible viable options in treatment ofacute ischemic stroke. In a systematic review of six uncontrolled, single-center trials, involvinga total of 300 patients, of intra-cranial stenting in symptomatic intracranial arterial stenosis, therate of technical success (reduction to stenosis of <50%) ranged from 90-98%, and the rate ofmajor peri-procedural complications ranged from 4-10%. The rates of restenosis and/or strokefollowing the treatment were also favorable.[92] This data suggests that a large, randomizedcontrolled trial is needed to more completely evaluate the possible therapeutic advantage ofthis treatment.

Secondary prevention of ischemic stroke

Anticoagulation can prevent recurrent stroke. Among patients with nonvalvular atrialfibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reducestroke by 20%.[93] However, a recent meta-analysis suggests harm from anti-coagulationstarted early after an embolic stroke.[94] Stroke prevention treatment for atrial fibrillation isdetermined according to the CHADS/CHADS2 system. The most widely used anticoagulant toprevent thromboembolic stroke in patients with nonvalvular atrial fibrillation is the oral agentWarfarin while dabigatran is a new alternative which does not require prothrombin timemonitoring.

If studies show carotid stenosis, and the patient has residual function in the affected side,carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence ifperformed rapidly after stroke.

Treatment of hemorrhagic stroke

Patients with intracerebral hemorrhage require neurosurgical evaluation to detect and treat thecause of the bleeding, although many may not need surgery. Anticoagulants andantithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be usedin intracerebral hemorrhage. Patients are monitored for changes in the level of consciousness,


17 of 31 13/03/11 10:42 PM

and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.

Care and rehabilitationStroke rehabilitation is the process by which patients with disabling strokes undergo treatmentto help them return to normal life as much as possible by regaining and relearning the skills ofeveryday living. It also aims to help the survivor understand and adapt to difficulties, preventsecondary complications and educate family members to play a supporting role.

A rehabilitation team is usually multidisciplinary as it involves staff with different skillsworking together to help the patient. These include nursing staff, physiotherapy, occupationaltherapy, speech and language therapy, and usually a physician trained in rehabilitationmedicine. Some teams may also include psychologists, social workers, and pharmacists sinceat least one third of the patients manifest post stroke depression. Validated instruments such asthe Barthel scale may be used to assess the likelihood of a stroke patient being able to manageat home with or without support subsequent to discharge from hospital.

Good nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, andmonitoring vital signs such as temperature, pulse, and blood pressure. Stroke rehabilitationbegins almost immediately.

For most stroke patients, physical therapy (PT) and occupational therapy (OT), speech-language pathology (SLP) are the cornerstones of the rehabilitation process. Often, assistivetechnology such as a wheelchair, walkers, canes, and orthosis may be beneficial. PT and OThave overlapping areas of working but their main attention fields are; PT involves re-learningfunctions as transferring, walking and other gross motor functions. OT focusses on exercisesand training to help relearn everyday activities known as the Activities of daily living (ADLs)such as eating, drinking, dressing, bathing, cooking, reading and writing, and toileting. Speechand language therapy is appropriate for patients with the speech production disorders:dysarthria and apraxia of speech, aphasia, cognitive-communication impairments and/ordysphagia (problems with swallowing).

Patients may have particular problems, such as complete or partial inability to swallow, whichcan cause swallowed material to pass into the lungs and cause aspiration pneumonia. Thecondition may improve with time, but in the interim, a nasogastric tube may be inserted,enabling liquid food to be given directly into the stomach. If swallowing is still deemed unsafe,then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remainindefinitely.

Stroke rehabilitation should be started as quickly as possible and can last anywhere from a fewdays to over a year. Most return of function is seen in the first few months, and thenimprovement falls off with the "window" considered officially by U.S. state rehabilitation unitsand others to be closed after six months, with little chance of further improvement. However,patients have been known to continue to improve for years, regaining and strengtheningabilities like writing, walking, running, and talking. Daily rehabilitation exercises shouldcontinue to be part of the stroke patient's routine. Complete recovery is unusual but not


18 of 31 13/03/11 10:42 PM

impossible and most patients will improve to some extent : proper diet and exercise are knownto help the brain to recover.

Prognosis

Disability affects 75% of stroke survivors enough to decrease their employability.[95] Strokecan affect patients physically, mentally, emotionally, or a combination of the three. The resultsof stroke vary widely depending on size and location of the lesion.[96] Dysfunctionscorrespond to areas in the brain that have been damaged.

Some of the physical disabilities that can result from stroke include muscle weakness,numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learnedmovements), difficulties carrying out daily activities, appetite loss, speech loss, vision loss, andpain. If the stroke is severe enough, or in a certain location such as parts of the brainstem,coma or death can result.

Emotional problems resulting from stroke can result from direct damage to emotional centersin the brain or from frustration and difficulty adapting to new limitations. Post-strokeemotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions),mania, apathy, and psychosis.

30 to 50% of stroke survivors suffer post stroke depression, which is characterized by lethargy,irritability, sleep disturbances, lowered self esteem, and withdrawal.[97] Depression can reducemotivation and worsen outcome, but can be treated with antidepressants.

Emotional lability, another consequence of stroke, causes the patient to switch quickly betweenemotional highs and lows and to express emotions inappropriately, for instance with an excessof laughing or crying with little or no provocation. While these expressions of emotion usuallycorrespond to the patient's actual emotions, a more severe form of emotional lability causespatients to laugh and cry pathologically, without regard to context or emotion.[95] Somepatients show the opposite of what they feel, for example crying when they are happy.[98]Emotional lability occurs in about 20% of stroke patients.

Cognitive deficits resulting from stroke include perceptual disorders, speech problems,dementia, and problems with attention and memory. A stroke sufferer may be unaware of his orher own disabilities, a condition called anosognosia. In a condition called hemispatial neglect,a patient is unable to attend to anything on the side of space opposite to the damagedhemisphere.

Up to 10% of all stroke patients develop seizures, most commonly in the week subsequent tothe event; the severity of the stroke increases the likelihood of a seizure.[99][100]

Epidemiology


19 of 31 13/03/11 10:42 PM

Hippocrates first describedthe sudden paralysis that isoften associated withstroke.

Stroke could soon be the most common cause of death worldwide.[101] Stroke is currently thesecond leading cause of death in the Western world, ranking after heart disease and beforecancer,[2] and causes 10% of deaths worldwide.[102] Geographic disparities in stroke incidencehave been observed, including the existence of a "stroke belt" in the southeastern UnitedStates, but causes of these disparities have not been explained.

The incidence of stroke increases exponentially from 30 years of age, and etiology varies byage.[103] Advanced age is one of the most significant stroke risk factors. 95% of strokes occurin people age 45 and older, and two-thirds of strokes occur in those over the age of 65.[97][19]A person's risk of dying if he or she does have a stroke also increases with age. However,stroke can occur at any age, including in childhood.

Family members may have a genetic tendency for stroke or share a lifestyle that contributes tostroke. Higher levels of Von Willebrand factor are more common amongst people who havehad ischemic stroke for the first time.[104] The results of this study found that the onlysignificant genetic factor was the person's blood type. Having had a stroke in the past greatlyincreases one's risk of future strokes.

Men are 25% more likely to suffer strokes than women,[19] yet 60% of deaths from strokeoccur in women.[98] Since women live longer, they are older on average when they have theirstrokes and thus more often killed (NIMH 2002).[19] Some risk factors for stroke apply only towomen. Primary among these are pregnancy, childbirth, menopause and the treatment thereof(HRT).

HistoryEpisodes of stroke and familial stroke have been reported fromthe 2nd millennium BC onward in ancient Mesopotamia andPersia.[105] Hippocrates (460 to 370 BC) was first to describe thephenomenon of sudden paralysis that is often associated withischemia. Apoplexy, from the Greek word meaning "struck downwith violence,” first appeared in Hippocratic writings to describethis phenomenon.[106][107]

The word stroke was used as a synonym for apoplectic seizure asearly as 1599,[108] and is a fairly literal translation of the Greekterm.

In 1658, in his Apoplexia, Johann Jacob Wepfer (1620–1695)identified the cause of hemorrhagic stroke when he suggestedthat people who had died of apoplexy had bleeding in theirbrains.[106][19] Wepfer also identified the main arteries supplying the brain, the vertebral andcarotid arteries, and identified the cause of ischemic stroke [also known as cerebral infarction]


20 of 31 13/03/11 10:42 PM

when he suggested that apoplexy might be caused by a blockage to those vessels.[19]

Rudolf Virchow first described the mechanism of thromboembolism as a major factor.[109]

External LinksImaging CVA (http://rad.usuhs.edu/medpix/master.php3?mode=image_finder&action=search&srchstr=stroke#top) CT, MR, Angiography of Stroke

References^ Sims NR, Muyderman H (September2009). "Mitochondria, oxidative metabolismand cell death in stroke". Biochimica etBiophysica Acta 1802 (1): 80–91.doi:10.1016/j.bbadis.2009.09.003(http://dx.doi.org/10.1016%2Fj.bbadis.2009.09.003) .PMID 19751827(http://www.ncbi.nlm.nih.gov/pubmed/19751827) .

1.

^ a b c d e f g h i j k l m Donnan GA, FisherM, Macleod M, Davis SM (May 2008)."Stroke". Lancet 371 (9624): 1612–23.doi:10.1016/S0140-6736(08)60694-7(http://dx.doi.org/10.1016%2FS0140-6736%2808%2960694-7) . PMID 18468545(http://www.ncbi.nlm.nih.gov/pubmed/18468545) .

2.

^ Feigin VL (2005). "Stroke epidemiologyin the developing world". Lancet 365 (9478):2160–1.doi:10.1016/S0140-6736(05)66755-4(http://dx.doi.org/10.1016%2FS0140-6736%2805%2966755-4) . PMID 15978910(http://www.ncbi.nlm.nih.gov/pubmed/15978910) .

3.

^ World Health Organisation (1978).Cerebrovascular Disorders (OffsetPublications). Geneva: World HealthOrganization. ISBN 9241700432.OCLC 4757533 (http://www.worldcat.org/oclc/4757533) .

4.

^ Kidwell CS, Warach S (December 2003)."Acute ischemic cerebrovascular syndrome:diagnostic criteria". Stroke 34 (12): 2995–8.doi:10.1161/01.STR.0000098902.69855.A9(http://dx.doi.org/10.1161%2F01.STR.0000098902.69855.A9) . PMID 14605325(http://www.ncbi.nlm.nih.gov/pubmed/14605325) .

5.

^ "Brain Basics: Preventing Stroke"(http://www.ninds.nih.gov/disorders/stroke/preventing_stroke.htm) . National Instituteof Neurological Disorders and Stroke.http://www.ninds.nih.gov/disorders/stroke/preventing_stroke.htm. Retrieved2009-10-24.

6.

^ Shuaib A, Hachinski VC (September1991). "Mechanisms and management ofstroke in the elderly"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1335826) . CMAJ 145 (5): 433–43.PMC 1335826(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1335826) . PMID 1878825(http://www.ncbi.nlm.nih.gov/pubmed/1878825) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1335826.

7.

^ a b Stam J (April 2005). "Thrombosis ofthe cerebral veins and sinuses". The NewEngland Journal of Medicine 352 (17):1791–8. doi:10.1056/NEJMra042354(http://dx.doi.org/10.1056%2FNEJMra042354) .PMID 15858188(http://www.ncbi.nlm.nih.gov/pubmed/15858188) .

8.

^ Guercini F, Acciarresi M, Agnelli G,Paciaroni M (April 2008). "Cryptogenicstroke: time to determine aetiology". Journalof Thrombosis and Haemostasis 6 (4):549–54.doi:10.1111/j.1538-7836.2008.02903.x(http://dx.doi.org/10.1111%2Fj.1538-7836.2008.02903.x) .PMID 18208534(http://www.ncbi.nlm.nih.gov/pubmed/18208534) .

9.

^ Bamford J, Sandercock P, Dennis M, Burn10.


21 of 31 13/03/11 10:42 PM

J, Warlow C (June 1991). "Classification andnatural history of clinically identifiablesubtypes of cerebral infarction". Lancet 337(8756): 1521–6.doi:10.1016/0140-6736(91)93206-O(http://dx.doi.org/10.1016%2F0140-6736%2891%2993206-O) . PMID 1675378(http://www.ncbi.nlm.nih.gov/pubmed/1675378) . Later publications distinguishbetween "syndrome" and "infarct", based onevidence from imaging. "Syndrome" may bereplaced by "hemorrhage" if imagingdemonstrates a bleed. See Internet StrokeCenter. "Oxford Stroke Scale"(http://www.strokecenter.org/trials/scales/oxford.html) . http://www.strokecenter.org/trials/scales/oxford.html. Retrieved2008-11-14.^ Bamford JM (2000). "The role of theclinical examination in the subclassificationof stroke". Cerebrovascular Diseases 10Suppl 4: 2–4. doi:10.1159/000047582(http://dx.doi.org/10.1159%2F000047582) .PMID 11070389(http://www.ncbi.nlm.nih.gov/pubmed/11070389) .

11.

^ Adams HP, Bendixen BH, Kappelle LJ, etal. (January 1993). "Classification of subtypeof acute ischemic stroke. Definitions for usein a multicenter clinical trial. TOAST. Trialof Org 10172 in Acute Stroke Treatment"(http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=7678184) . Stroke 24 (1): 35–41.PMID 7678184(http://www.ncbi.nlm.nih.gov/pubmed/7678184) . http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=7678184.

12.

^ Goldstein LB, Simel DL (May 2005). "Isthis patient having a stroke?". JAMA 293(19): 2391–402.doi:10.1001/jama.293.19.2391(http://dx.doi.org/10.1001%2Fjama.293.19.2391) .PMID 15900010(http://www.ncbi.nlm.nih.gov/pubmed/15900010) .

13.

^ Harbison J, Massey A, Barnett L, HodgeD, Ford GA (June 1999). "Rapid ambulanceprotocol for acute stroke". Lancet 353(9168): 1935.doi:10.1016/S0140-6736(99)00966-6(http://dx.doi.org/10.1016%2FS0140-6736%2899%2900966-6) . PMID 10371574(http://www.ncbi.nlm.nih.gov/pubmed/10371574) .

14.

^ Kidwell CS, Saver JL, Schubert GB,Eckstein M, Starkman S (1998). "Design andretrospective analysis of the Los AngelesPrehospital Stroke Screen (LAPSS)".Prehospital Emergency Care 2 (4): 267–73.doi:10.1080/10903129808958878(http://dx.doi.org/10.1080%2F10903129808958878) .PMID 9799012(http://www.ncbi.nlm.nih.gov/pubmed/9799012) .

15.

^ Kothari RU, Pancioli A, Liu T, Brott T,Broderick J (April 1999). "CincinnatiPrehospital Stroke Scale: reproducibility andvalidity". Annals of Emergency Medicine 33(4): 373–8.doi:10.1016/S0196-0644(99)70299-4(http://dx.doi.org/10.1016%2FS0196-0644%2899%2970299-4) . PMID 10092713(http://www.ncbi.nlm.nih.gov/pubmed/10092713) .

16.

^ a b National Institute for Health andClinical Excellence. Clinical guideline 68:Stroke (http://guidance.nice.org.uk/CG68) .London, 2008.

17.

^ Nor AM, Davis J, Sen B, et al. (November2005). "The Recognition of Stroke in theEmergency Room (ROSIER) scale:development and validation of a strokerecognition instrument". Lancet Neurology 4(11): 727–34.doi:10.1016/S1474-4422(05)70201-5(http://dx.doi.org/10.1016%2FS1474-4422%2805%2970201-5) . PMID 16239179(http://www.ncbi.nlm.nih.gov/pubmed/16239179) .

18.

^ a b c d e f g h i National Institute ofNeurological Disorders and Stroke (NINDS)(1999). "Stroke: Hope Through Research"(http://www.ninds.nih.gov/disorders/stroke/detail_stroke.htm) . National Institutes ofHealth. http://www.ninds.nih.gov/disorders/stroke/detail_stroke.htm.

19.

^ Ay H, Furie KL, Singhal A, Smith WS,Sorensen AG, Koroshetz WJ (November2005). "An evidence-based causativeclassification system for acute ischemicstroke". Annals of Neurology 58 (5): 688–97.doi:10.1002/ana.20617 (http://dx.doi.org/10.1002%2Fana.20617) . PMID 16240340(http://www.ncbi.nlm.nih.gov/pubmed/16240340) .

20.

^ Deb P, Sharma S, Hassan KM (June 2010)."Pathophysiologic mechanisms of acuteischemic stroke: An overview with emphasison therapeutic significance beyond

21.


22 of 31 13/03/11 10:42 PM

thrombolysis.". Pathophysiology : theofficial journal of the International Societyfor Pathophysiology / ISP 17 (3): 197–218.doi:10.1016/j.pathophys.2009.12.001(http://dx.doi.org/10.1016%2Fj.pathophys.2009.12.001) .PMID 20074922(http://www.ncbi.nlm.nih.gov/pubmed/20074922) .^ Brunner and Suddarth's Textbook onMedical-Surgical Nursing, 11th Edition

22.

^ Lees KR, Zivin JA, Ashwood T, et al.(February 2006). "NXY-059 for acuteischemic stroke". The New England Journalof Medicine 354 (6): 588–600.doi:10.1056/NEJMoa052980(http://dx.doi.org/10.1056%2FNEJMoa052980) .PMID 16467546(http://www.ncbi.nlm.nih.gov/pubmed/16467546) .

23.

^ Hill MD (November 2005). "Diagnosticbiomarkers for stroke: a stroke neurologist'sperspective". Clinical Chemistry 51 (11):2001–2. doi:10.1373/clinchem.2005.056382(http://dx.doi.org/10.1373%2Fclinchem.2005.056382) .PMID 16244286(http://www.ncbi.nlm.nih.gov/pubmed/16244286) .

24.

^ Chalela JA, Kidwell CS, Nentwich LM, etal. (January 2007). "Magnetic resonanceimaging and computed tomography inemergency assessment of patients withsuspected acute stroke: a prospectivecomparison"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1859855) . Lancet 369 (9558): 293–8.doi:10.1016/S0140-6736(07)60151-2(http://dx.doi.org/10.1016%2FS0140-6736%2807%2960151-2) . PMC 1859855(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1859855) . PMID 17258669(http://www.ncbi.nlm.nih.gov/pubmed/17258669) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1859855.

25.

^ Kidwell CS, Chalela JA, Saver JL, et al.(October 2004). "Comparison of MRI andCT for detection of acute intracerebralhemorrhage". JAMA 292 (15): 1823–30.doi:10.1001/jama.292.15.1823(http://dx.doi.org/10.1001%2Fjama.292.15.1823) .PMID 15494579

26.

(http://www.ncbi.nlm.nih.gov/pubmed/15494579) .^ a b Straus SE, Majumdar SR, McAlister FA(September 2002). "New evidence for strokeprevention: scientific review". JAMA 288(11): 1388–95.doi:10.1001/jama.288.11.1388(http://dx.doi.org/10.1001%2Fjama.288.11.1388) .PMID 12234233(http://www.ncbi.nlm.nih.gov/pubmed/12234233) .

27.

^ Goldstein LB, Adams R, Alberts MJ, et al.(June 2006). "Primary prevention ofischemic stroke: a guideline from theAmerican Heart Association/AmericanStroke Association Stroke Council:cosponsored by the AtheroscleroticPeripheral Vascular Disease InterdisciplinaryWorking Group; Cardiovascular NursingCouncil; Clinical Cardiology Council;Nutrition, Physical Activity, and MetabolismCouncil; and the Quality of Care andOutcomes Research InterdisciplinaryWorking Group: the American Academy ofNeurology affirms the value of thisguideline". Stroke 37 (6): 1583–633.doi:10.1161/01.STR.0000223048.70103.F1(http://dx.doi.org/10.1161%2F01.STR.0000223048.70103.F1). PMID 16675728(http://www.ncbi.nlm.nih.gov/pubmed/16675728) .

28.

^ a b c NPS Prescribing Practice Review 44:Antiplatelets and anticoagulants in strokeprevention (2009). Available at nps.org.au(http://www.nps.org.au/health_professionals/publications/prescribing_practice_review/current/nps_prescribing_practice_review_44)

29.

^ a b Antithrombotic Trialists' Collaboration(January 2002). "Collaborative meta-analysisof randomised trials of antiplatelet therapyfor prevention of death, myocardialinfarction, and stroke in high risk patients"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=64503) . BMJ 324 (7329): 71–86.doi:10.1136/bmj.324.7329.71(http://dx.doi.org/10.1136%2Fbmj.324.7329.71) . PMC 64503(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64503) . PMID 11786451(http://www.ncbi.nlm.nih.gov/pubmed/11786451) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&

30.


23 of 31 13/03/11 10:42 PM

artid=64503.^ "MRC trial of treatment of mildhypertension: principal results. MedicalResearch Council Working Party"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1416260) . British Medical Journal291 (6488): 97–104. July 1985.doi:10.1136/bmj.291.6488.97(http://dx.doi.org/10.1136%2Fbmj.291.6488.97) .PMC 1416260(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1416260) . PMID 2861880(http://www.ncbi.nlm.nih.gov/pubmed/2861880) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1416260.

31.

^ Thomson R (2009). "Evidence basedimplementation of complex interventions".BMJ 339: b3124. doi:10.1136/bmj.b3124(http://dx.doi.org/10.1136%2Fbmj.b3124) .PMID 19675081(http://www.ncbi.nlm.nih.gov/pubmed/19675081) .

32.

^ Hankey GJ (August 1999). "Smoking andrisk of stroke". Journal of CardiovascularRisk 6 (4): 207–11. PMID 10501270(http://www.ncbi.nlm.nih.gov/pubmed/10501270) .

33.

^ Wannamethee SG, Shaper AG, WhincupPH, Walker M (July 1995). "Smokingcessation and the risk of stroke inmiddle-aged men". JAMA 274 (2): 155–60.doi:10.1001/jama.274.2.155(http://dx.doi.org/10.1001%2Fjama.274.2.155) .PMID 7596004(http://www.ncbi.nlm.nih.gov/pubmed/7596004) .

34.

^ Reynolds K, Lewis B, Nolen JD, et al.(February 2003). "Alcohol consumption andrisk of stroke: a meta-analysis". JAMA 289(5): 579–88. doi:10.1001/jama.289.5.579(http://dx.doi.org/10.1001%2Fjama.289.5.579) .PMID 12578491(http://www.ncbi.nlm.nih.gov/pubmed/12578491) .

35.

^ Sloan MA, Kittner SJ, Rigamonti D, PriceTR (September 1991). "Occurrence of strokeassociated with use/abuse of drugs".Neurology 41 (9): 1358–64. PMID 1891081(http://www.ncbi.nlm.nih.gov/pubmed/1891081) .

36.

^ "Stroke Risk Factors"(http://www.AmericanHeart.org

37.

/presenter.jhtml?identifier=4716) . AmericanHeart Association. 2007.http://www.AmericanHeart.org/presenter.jhtml?identifier=4716. RetrievedJanuary 22, 2007.^ Gorelick PB (1987). "Alcohol and stroke"(http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=3810763) . Stroke; a Journal ofCerebral Circulation 18 (1): 268–71.PMID 3810763(http://www.ncbi.nlm.nih.gov/pubmed/3810763) . http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=3810763.

38.

^ Westover AN, McBride S, Haley RW(April 2007). "Stroke in young adults whoabuse amphetamines or cocaine: apopulation-based study of hospitalizedpatients". Archives of General Psychiatry 64(4): 495–502. doi:10.1001/archpsyc.64.4.495(http://dx.doi.org/10.1001%2Farchpsyc.64.4.495) .PMID 17404126(http://www.ncbi.nlm.nih.gov/pubmed/17404126) .

39.

^ Cantu C, Arauz A, Murillo-Bonilla LM,López M, Barinagarrementeria F (2003)."Stroke associated with sympathomimeticscontained in over-the-counter cough andcold drugs". Stroke 34 (7): 1667–72.doi:10.1161/01.STR.0000075293.45936.FA(http://dx.doi.org/10.1161%2F01.STR.0000075293.45936.FA) . PMID 12791938(http://www.ncbi.nlm.nih.gov/pubmed/12791938) .

40.

^ Ezekowitz JA, Straus SE, Majumdar SR,McAlister FA (December 2003). "Stroke:strategies for primary prevention". AmericanFamily Physician 68 (12): 2379–86.PMID 14705756(http://www.ncbi.nlm.nih.gov/pubmed/14705756) .

41.

^ a b c d Ederle J, Brown MM (October2006). "The evidence for medicine versussurgery for carotid stenosis". EuropeanJournal of Radiology 60 (1): 3–7.doi:10.1016/j.ejrad.2006.05.021(http://dx.doi.org/10.1016%2Fj.ejrad.2006.05.021) .PMID 16920313(http://www.ncbi.nlm.nih.gov/pubmed/16920313) .

42.

^ Whisnant JP (1996). "Effectiveness versusefficacy of treatment of hypertension forstroke prevention". Neurology 46 (2): 301–7.PMID 8614485

43.


24 of 31 13/03/11 10:42 PM

(http://www.ncbi.nlm.nih.gov/pubmed/8614485) .^ Collins R, Peto R, MacMahon S, et al.(1990). "Blood pressure, stroke, andcoronary heart disease. Part 2, Short-termreductions in blood pressure: overview ofrandomised drug trials in theirepidemiological context". Lancet 335(8693): 827–38.doi:10.1016/0140-6736(90)90944-Z(http://dx.doi.org/10.1016%2F0140-6736%2890%2990944-Z) . PMID 1969567(http://www.ncbi.nlm.nih.gov/pubmed/1969567) .

44.

^ Psaty BM, Lumley T, Furberg CD, et al.(2003). "Health outcomes associated withvarious antihypertensive therapies used asfi rst-line agents: a network meta-analysis".JAMA 289 (19): 2534–44.doi:10.1001/jama.289.19.2534(http://dx.doi.org/10.1001%2Fjama.289.19.2534) .PMID 12759325(http://www.ncbi.nlm.nih.gov/pubmed/12759325) .

45.

^ a b "Cholesterol, diastolic blood pressure,and stroke: 13,000 strokes in 450,000 peoplein 45 prospective cohorts. Prospectivestudies collaboration". Lancet 346(8991-8992): 1647–53. 1995.doi:10.1016/S0140-6736(95)92836-7(http://dx.doi.org/10.1016%2FS0140-6736%2895%2992836-7) . PMID 8551820(http://www.ncbi.nlm.nih.gov/pubmed/8551820) .

46.

^ Gueyffier F, Boissel JP, Boutitie F, et al.(1997). "Effect of antihypertensive treatmentin patients having already suffered fromstroke. Gathering the evidence. TheINDANA (INdividual Data ANalysis ofAntihypertensive intervention trials) ProjectCollaborators". Stroke 28 (12): 2557–62.PMID 9412649(http://www.ncbi.nlm.nih.gov/pubmed/9412649) .

47.

^ Gueyffier F, Bulpitt C, Boissel JP, et al.(1999). "Antihypertensive drugs in very oldpeople: a subgroup meta-analysis ofrandomised controlled trials. INDANAGroup". Lancet 353 (9155): 793–6.doi:10.1016/S0140-6736(98)08127-6(http://dx.doi.org/10.1016%2FS0140-6736%2898%2908127-6) . PMID 10459960(http://www.ncbi.nlm.nih.gov/pubmed/10459960) .

48.

^ Staessen JA, Gasowski J, Wang JG, et al.(2000). "Risks of untreated and treatedisolated systolic hypertension in the elderly:meta-analysis of outcome trials". Lancet 355(9207): 865–72.doi:10.1016/S0140-6736(99)07330-4(http://dx.doi.org/10.1016%2FS0140-6736%2899%2907330-4) . PMID 10752701(http://www.ncbi.nlm.nih.gov/pubmed/10752701) .

49.

^ Beckett NS, Peters R, Fletcher AE, et al.(2008). "Treatment of Hypertension inPatients 80 Years of Age or Older". N. Engl.J. Med. 358 (18): 1887–98.doi:10.1056/NEJMoa0801369(http://dx.doi.org/10.1056%2FNEJMoa0801369) .PMID 18378519(http://www.ncbi.nlm.nih.gov/pubmed/18378519) .

50.

^ a b Neal B, MacMahon S, Chapman N(2000). "Effects of ACE inhibitors, calciumantagonists, and other blood-pressure-lowering drugs: results of prospectivelydesigned overviews of randomised trials.Blood Pressure Lowering TreatmentTrialists' Collaboration". Lancet 356 (9246):1955–64.doi:10.1016/S0140-6736(00)03307-9(http://dx.doi.org/10.1016%2FS0140-6736%2800%2903307-9) . PMID 11130523(http://www.ncbi.nlm.nih.gov/pubmed/11130523) .

51.

^ The Allhat Officers And Coordinators ForThe Allhat Collaborative Research Group,(2002). "Major outcomes in high-riskhypertensive patients randomized toangiotensin-converting enzyme inhibitor orcalcium channel blocker vs diuretic: TheAntihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial(ALLHAT)". JAMA 288 (23): 2981–97.doi:10.1001/jama.288.23.2981(http://dx.doi.org/10.1001%2Fjama.288.23.2981) .PMID 12479763(http://www.ncbi.nlm.nih.gov/pubmed/12479763) .

52.

^ Wolf PA, Abbott RD, Kannel WB (1987)."Atrial fibrillation: a major contributor tostroke in the elderly. The FraminghamStudy". Arch. Intern. Med. 147 (9): 1561–4.doi:10.1001/archinte.147.9.1561(http://dx.doi.org/10.1001%2Farchinte.147.9.1561) .PMID 3632164

53.


25 of 31 13/03/11 10:42 PM

(http://www.ncbi.nlm.nih.gov/pubmed/3632164) .^ Fuster V, Rydén LE, Cannom DS, et al.(2006). "ACC/AHA/ESC 2006 Guidelinesfor the Management of Patients with AtrialFibrillation: a report of the AmericanCollege of Cardiology/American HeartAssociation Task Force on PracticeGuidelines and the European Society ofCardiology Committee for PracticeGuidelines (Writing Committee to Revisethe 2001 Guidelines for the Management ofPatients With Atrial Fibrillation): developedin collaboration with the European HeartRhythm Association and the Heart RhythmSociety". Circulation 114 (7): e257–354.doi:10.1161/CIRCULATIONAHA.106.177292 (http://dx.doi.org/10.1161%2FCIRCULATIONAHA.106.177292) . PMID 16908781(http://www.ncbi.nlm.nih.gov/pubmed/16908781) .

54.

^ Iso H, Jacobs DR, Wentworth D, NeatonJD, Cohen JD (1989). "Serum cholesterollevels and six-year mortality from stroke in350,977 men screened for the multiple riskfactor intervention trial". N. Engl. J. Med.320 (14): 904–10.doi:10.1056/NEJM198904063201405(http://dx.doi.org/10.1056%2FNEJM198904063201405) .PMID 2619783(http://www.ncbi.nlm.nih.gov/pubmed/2619783) .

55.

^ a b O'Regan C, Wu P, Arora P, Perri D,Mills EJ (2008). "Statin therapy in strokeprevention: a meta-analysis involving121,000 patients". Am. J. Med. 121 (1):24–33. doi:10.1016/j.amjmed.2007.06.033(http://dx.doi.org/10.1016%2Fj.amjmed.2007.06.033) .PMID 18187070(http://www.ncbi.nlm.nih.gov/pubmed/18187070) .

56.

^ Hebert PR, Gaziano JM, Hennekens CH(1995). "An overview of trials of cholesterollowering and risk of stroke". Arch. Intern.Med. 155 (1): 50–5.doi:10.1001/archinte.155.1.50(http://dx.doi.org/10.1001%2Farchinte.155.1.50) .PMID 7802520(http://www.ncbi.nlm.nih.gov/pubmed/7802520) .

57.

^ "Intensive blood-glucose control withsulphonylureas or insulin compared withconventional treatment and risk ofcomplications in patients with type 2

58.

diabetes (UKPDS 33). UK ProspectiveDiabetes Study (UKPDS) Group". Lancet352 (9131): 837–53. 1998.doi:10.1016/S0140-6736(98)07019-6(http://dx.doi.org/10.1016%2FS0140-6736%2898%2907019-6) . PMID 9742976(http://www.ncbi.nlm.nih.gov/pubmed/9742976) .^ Dormandy JA, Charbonnel B, Eckland DJ,et al. (2005). "Secondary prevention ofmacrovascular events in patients with type 2diabetes in the PROactive Study(PROspective pioglitAzone Clinical Trial InmacroVascular Events): a randomisedcontrolled trial". Lancet 366 (9493):1279–89.doi:10.1016/S0140-6736(05)67528-9(http://dx.doi.org/10.1016%2FS0140-6736%2805%2967528-9) . PMID 16214598(http://www.ncbi.nlm.nih.gov/pubmed/16214598) .

59.

^ Johnson ES, Lanes SF, Wentworth CE,Satterfield MH, Abebe BL, Dicker LW(1999). "A metaregression analysis of thedose-response effect of aspirin on stroke".Arch. Intern. Med. 159 (11): 1248–53.doi:10.1001/archinte.159.11.1248(http://dx.doi.org/10.1001%2Farchinte.159.11.1248) .PMID 10371234(http://www.ncbi.nlm.nih.gov/pubmed/10371234) .

60.

^ a b Hankey GJ, Sudlow CL, Dunbabin DW(2000). "Thienopyridine derivatives(ticlopidine, clopidogrel) versus aspirin forpreventing stroke and other serious vascularevents in high vascular risk patients".Cochrane Database Syst Rev (2):CD001246.doi:10.1002/14651858.CD001246(http://dx.doi.org/10.1002%2F14651858.CD001246) .PMID 10796426(http://www.ncbi.nlm.nih.gov/pubmed/10796426) .

61.

^ Halkes PH, van Gijn J, Kappelle LJ,Koudstaal PJ, Algra A (2006). "Aspirin plusdipyridamole versus aspirin alone aftercerebral ischaemia of arterial origin(ESPRIT): randomised controlled trial".Lancet 367 (9523): 1665–73.doi:10.1016/S0140-6736(06)68734-5(http://dx.doi.org/10.1016%2FS0140-6736%2806%2968734-5) . PMID 16714187(http://www.ncbi.nlm.nih.gov/pubmed

62.


26 of 31 13/03/11 10:42 PM

/16714187) .^ Algra A; Halkes, PH; Van Gijn, J;Kappelle, LJ; Koudstaal, PJ; Algra, A(2007). "Medium intensity oralanticoagulants versus aspirin after cerebralischaemia of arterial origin (ESPRIT): arandomised controlled trial". Lancet Neurol6 (2): 115–24.doi:10.1016/S1474-4422(06)70685-8(http://dx.doi.org/10.1016%2FS1474-4422%2806%2970685-8) . PMID 17239798(http://www.ncbi.nlm.nih.gov/pubmed/17239798) .

63.

^ Hart RG, Halperin JL, McBride R,Benavente O, Man-Son-Hing M, KronmalRA (2000). "Aspirin for the primaryprevention of stroke and other majorvascular events: meta-analysis andhypotheses". Arch. Neurol. 57 (3): 326–32.doi:10.1001/archneur.57.3.326(http://dx.doi.org/10.1001%2Farchneur.57.3.326) .PMID 10714657(http://www.ncbi.nlm.nih.gov/pubmed/10714657) .

64.

^ Bartolucci AA, Howard G (2006). "Meta-analysis of data from the six primaryprevention trials of cardiovascular eventsusing aspirin". Am. J. Cardiol. 98 (6):746–50. doi:10.1016/j.amjcard.2006.04.012(http://dx.doi.org/10.1016%2Fj.amjcard.2006.04.012) .PMID 16950176(http://www.ncbi.nlm.nih.gov/pubmed/16950176) .

65.

^ Berger JS, Roncaglioni MC, Avanzini F,Pangrazzi I, Tognoni G, Brown DL (2006)."Aspirin for the primary prevention ofcardiovascular events in women and men: asex-specific meta-analysis of randomizedcontrolled trials". JAMA 295 (3): 306–13.doi:10.1001/jama.295.3.306(http://dx.doi.org/10.1001%2Fjama.295.3.306) .PMID 16418466(http://www.ncbi.nlm.nih.gov/pubmed/16418466) .

66.

^ Yerman T, Gan WQ, Sin DD (2007). "Theinfluence of gender on the effects of aspirinin preventing myocardial infarction"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2131749) . BMC Med 5: 29.doi:10.1186/1741-7015-5-29(http://dx.doi.org/10.1186%2F1741-7015-5-29) .PMC 2131749(http://www.pubmedcentral.gov

67.

/articlerender.fcgi?tool=pmcentrez&artid=2131749) . PMID 17949479(http://www.ncbi.nlm.nih.gov/pubmed/17949479) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2131749.^ Rothwell PM, Eliasziw M, Gutnikov SA,et al. (2003). "Analysis of pooled data fromthe randomised controlled trials ofendarterectomy for symptomatic carotidstenosis". Lancet 361 (9352): 107–16.doi:10.1016/S0140-6736(03)12228-3(http://dx.doi.org/10.1016%2FS0140-6736%2803%2912228-3) . PMID 12531577(http://www.ncbi.nlm.nih.gov/pubmed/12531577) .

68.

^ Ringleb PA, Chatellier G, Hacke W, et al.(2008). "Safety of endovascular treatment ofcarotid artery stenosis compared withsurgical treatment: a meta-analysis". J. Vasc.Surg. 47 (2): 350–5.doi:10.1016/j.jvs.2007.10.035(http://dx.doi.org/10.1016%2Fj.jvs.2007.10.035) .PMID 18241759(http://www.ncbi.nlm.nih.gov/pubmed/18241759) .

69.

^ Ederle J, Featherstone RL, Brown MM(2007). "Percutaneous transluminalangioplasty and stenting for carotid arterystenosis". Cochrane Database Syst Rev (4):CD000515.doi:10.1002/14651858.CD000515.pub3(http://dx.doi.org/10.1002%2F14651858.CD000515.pub3) .PMID 17943745(http://www.ncbi.nlm.nih.gov/pubmed/17943745) .

70.

^ Rothwell PM, Eliasziw M, Gutnikov SA,Warlow CP, Barnett HJ (2004)."Endarterectomy for symptomatic carotidstenosis in relation to clinical subgroups andtiming of surgery". Lancet 363 (9413):915–24.doi:10.1016/S0140-6736(04)15785-1(http://dx.doi.org/10.1016%2FS0140-6736%2804%2915785-1) . PMID 15043958(http://www.ncbi.nlm.nih.gov/pubmed/15043958) .

71.

^ Fairhead JF, Mehta Z, Rothwell PM(2005). "Population-based study of delays incarotid imaging and surgery and the risk ofrecurrent stroke". Neurology 65 (3): 371–5.doi:10.1212/01.wnl.0000170368.82460.b4(http://dx.doi.org/10.1212%2F01.wnl.0000170368.82460.b4)

72.


27 of 31 13/03/11 10:42 PM

. PMID 16087900(http://www.ncbi.nlm.nih.gov/pubmed/16087900) .^ U.S. Preventive Services Task Force(2007). "Screening for carotid arterystenosis: U.S. Preventive Services TaskForce recommendation statement". Ann.Intern. Med. 147 (12): 854–9.PMID 18087056(http://www.ncbi.nlm.nih.gov/pubmed/18087056) .

73.

^ Halliday A, Mansfield A, Marro J, et al.(2004). "Prevention of disabling and fatalstrokes by successful carotid endarterectomyin patients without recent neurologicalsymptoms: randomised controlled trial".Lancet 363 (9420): 1491–502.doi:10.1016/S0140-6736(04)16146-1(http://dx.doi.org/10.1016%2FS0140-6736%2804%2916146-1) . PMID 15135594(http://www.ncbi.nlm.nih.gov/pubmed/15135594) .

74.

^ Chambers BR, Donnan GA (2005)."Carotid endarterectomy for asymptomaticcarotid stenosis". Cochrane Database SystRev (4): CD001923.doi:10.1002/14651858.CD001923.pub2(http://dx.doi.org/10.1002%2F14651858.CD001923.pub2) .PMID 16235289(http://www.ncbi.nlm.nih.gov/pubmed/16235289) .

75.

^ Spence JD; Lees, K.; Spence, J. D.(September 2006). "Nutrition and strokeprevention" (http://stroke.ahajournals.org/cgi/content/full/37/9/2430) . Stroke 37 (9):2430–5.doi:10.1161/01.STR.0000236633.40160.ee(http://dx.doi.org/10.1161%2F01.STR.0000236633.40160.ee). PMID 16873712(http://www.ncbi.nlm.nih.gov/pubmed/16873712) . http://stroke.ahajournals.org/cgi/content/full/37/9/2430.

76.

^ Wang X, Qin X, Demirtas H, et al. (2007)."Efficacy of folic acid supplementation instroke prevention: a meta-analysis". Lancet369 (9576): 1876–82.doi:10.1016/S0140-6736(07)60854-X(http://dx.doi.org/10.1016%2FS0140-6736%2807%2960854-X) . PMID 17544768(http://www.ncbi.nlm.nih.gov/pubmed/17544768) .

77.

^ Lonn E, Yusuf S, Arnold MJ, et al. (2006)."Homocysteine lowering with folic acid andB vitamins in vascular disease". N. Engl. J.Med. 354 (15): 1567–77.

78.

doi:10.1056/NEJMoa060900(http://dx.doi.org/10.1056%2FNEJMoa060900) .PMID 16531613(http://www.ncbi.nlm.nih.gov/pubmed/16531613) .^ Toole JF, Malinow MR, Chambless LE, etal. (2004). "Lowering homocysteine inpatients with ischemic stroke to preventrecurrent stroke, myocardial infarction, anddeath: the Vitamin Intervention for StrokePrevention (VISP) randomized controlledtrial". JAMA 291 (5): 565–75.doi:10.1001/jama.291.5.565(http://dx.doi.org/10.1001%2Fjama.291.5.565) .PMID 14762035(http://www.ncbi.nlm.nih.gov/pubmed/14762035) .

79.

^ Heartscore.org (http://www.heartscore.org)80.^ Saver JL (2006). "Time is brain -quantified" (http://stroke.ahajournals.org/cgi/content/abstract/01.STR.0000196957.55928.abv1) . Stroke37 (37): 263–6.doi:10.1161/01.STR.0000196957.55928.ab(http://dx.doi.org/10.1161%2F01.STR.0000196957.55928.ab). PMID 16339467(http://www.ncbi.nlm.nih.gov/pubmed/16339467) . http://stroke.ahajournals.org/cgi/content/abstract/01.STR.0000196957.55928.abv1.

81.

^ The National Institute Of NeurologicalDisorders And Stroke Rt-Pa Stroke StudyGroup, (1995). "Tissue plasminogenactivator for acute ischemic stroke. TheNational Institute of Neurological Disordersand Stroke rt-PA Stroke Study Group"(http://content.nejm.org/cgi/content/full/333/24/1581) . New England Journal ofMedicine 333 (24): 1581–7.doi:10.1056/NEJM199512143332401(http://dx.doi.org/10.1056%2FNEJM199512143332401) .PMID 7477192(http://www.ncbi.nlm.nih.gov/pubmed/7477192) . http://content.nejm.org/cgi/content/full/333/24/1581.

82.

^ The European Cooperative Acute StrokeStudy (ECASS), (2008). "Thrombolysis withAlteplase 3 to 4.5 Hours after AcuteIschemic Stroke" (http://content.nejm.org/cgi/content/short/359/13/1317) . NewEngland Journal of Medicine 359 (13):1317–1329. doi:10.1056/NEJMoa0804656(http://dx.doi.org/10.1056%2FNEJMoa0804656) .PMID 18815396

83.


28 of 31 13/03/11 10:42 PM

(http://www.ncbi.nlm.nih.gov/pubmed/18815396) . http://content.nejm.org/cgi/content/short/359/13/1317.^ Dubinsky, R; Lai SM (2006). "Mortality ofstroke patients treated with thrombolysis:analysis of nationwide inpatient sample".Neurology 66 (11): 1742–1744.doi:10.1212/01.wnl.0000218306.35681.38(http://dx.doi.org/10.1212%2F01.wnl.0000218306.35681.38). PMID 16769953(http://www.ncbi.nlm.nih.gov/pubmed/16769953) .

84.

^ "Position Statement on the Use ofIntravenous Thrombolytic Therapy in theTreatment of Stroke" (http://www.aaem.org/positionstatements/thrombolytictherapy.shtml) . AmericanAcademy of Emergency Medicine.http://www.aaem.org/positionstatements/thrombolytictherapy.shtml. Retrieved2008-01-25.

85.

^ Lee M, Hong KS, Saver JL (May 2010)."Efficacy of intra-arterial fibrinolysis foracute ischemic stroke: meta-analysis ofrandomized controlled trials". Stroke 41 (5):932–7.doi:10.1161/STROKEAHA.109.574335(http://dx.doi.org/10.1161%2FSTROKEAHA.109.574335) .PMID 20360549(http://www.ncbi.nlm.nih.gov/pubmed/20360549) .

86.

^ Flint AC, Duckwiler GR, Budzik RF,Liebeskind DS, Smith WS (2007)."Mechanical thrombectomy of intracranialinternal carotid occlusion: pooled results ofthe MERCI and Multi MERCI Part I trials".Stroke 38 (4): 1274–80.doi:10.1161/01.STR.0000260187.33864.a7(http://dx.doi.org/10.1161%2F01.STR.0000260187.33864.a7). PMID 17332445(http://www.ncbi.nlm.nih.gov/pubmed/17332445) .

87.

^ Smith WS, Sung G, Starkman S, et al.(2005). "Safety and efficacy of mechanicalembolectomy in acute ischemic stroke:results of the MERCI trial"(http://stroke.ahajournals.org/cgi/content/full/36/7/1432) . Stroke 36 (7): 1432–8.doi:10.1161/01.STR.0000171066.25248.1d(http://dx.doi.org/10.1161%2F01.STR.0000171066.25248.1d). PMID 15961709(http://www.ncbi.nlm.nih.gov/pubmed/15961709) . http://stroke.ahajournals.org/cgi/content/full/36/7/1432.

88.

^ Lutsep HL, Rymer MM, Nesbit GM89.

(2008). "Vertebrobasilar revascularizationrates and outcomes in the MERCI andmulti-MERCI trials". J Stroke CerebrovascDis 17 (2): 55–7.doi:10.1016/j.jstrokecerebrovasdis.2007.11.003 (http://dx.doi.org/10.1016%2Fj.jstrokecerebrovasdis.2007.11.003) . PMID 18346645(http://www.ncbi.nlm.nih.gov/pubmed/18346645) .^ Smith WS (June 1, 2006). "Safety ofmechanical thrombectomy and intravenoustissue plasminogen activator in acuteischemic stroke. Results of the multiMechanical Embolus Removal in CerebralIschemia (MERCI) trial, part I"(http://www.ajnr.org/cgi/content/full/27/6/1177) . AJNR Am J Neuroradiol 27 (6):1177–82. PMID 16775259(http://www.ncbi.nlm.nih.gov/pubmed/16775259) . http://www.ajnr.org/cgi/content/full/27/6/1177.

90.

^ Smith WS, Sung G, Saver J, et al. (2008)."Mechanical thrombectomy for acuteischemic stroke: final results of the MultiMERCI trial". Stroke 39 (4): 1205–12.doi:10.1161/STROKEAHA.107.497115(http://dx.doi.org/10.1161%2FSTROKEAHA.107.497115) .PMID 18309168(http://www.ncbi.nlm.nih.gov/pubmed/18309168) .

91.

^ Derdeyn CP, Chimowitz MI (August2007). "Angioplasty and stenting foratherosclerotic intracranial stenosis:rationale for a randomized clinical trial".Neuroimaging Clin. N. Am. 17 (3): 355–63,viii–ix. doi:10.1016/j.nic.2007.05.001(http://dx.doi.org/10.1016%2Fj.nic.2007.05.001) .PMC 2040119(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=2040119) . PMID 17826637(http://www.ncbi.nlm.nih.gov/pubmed/17826637) .

92.

^ Hart RG, Pearce LA, Aguilar MI (2007)."Meta-analysis: antithrombotic therapy toprevent stroke in patients who havenonvalvular atrial fibrillation". Ann. Intern.Med. 146 (12): 857–67. PMID 17577005(http://www.ncbi.nlm.nih.gov/pubmed/17577005) .

93.

^ Paciaroni M, Agnelli G, Micheli S, Caso V(2007). "Efficacy and safety of anticoagulanttreatment in acute cardioembolic stroke: ameta-analysis of randomized controlledtrials". Stroke 38 (2): 423–30.doi:10.1161/01.STR.0000254600.92975.1f

94.


29 of 31 13/03/11 10:42 PM

(http://dx.doi.org/10.1161%2F01.STR.0000254600.92975.1f). PMID 17204681(http://www.ncbi.nlm.nih.gov/pubmed/17204681) . ACP JC synopsis(http://www.acpjc.org/Content/147/1/issue/ACPJC-2007-147-1-017.htm)^ a b Coffey C. Edward, Cummings JeffreyL, Starkstein Sergio, Robinson Robert(2000). Stroke - the American PsychiatricPress Textbook of Geriatric Neuropsychiatry(Second ed.). Washington DC: AmericanPsychiatric Press. pp. 601–617.

95.

^ Stanford Hospital & Clinics."Cardiovascular Diseases: Effects of Stroke"(http://www.stanfordhospital.com/healthLib/atoz/cardiac/effects.html) .http://www.stanfordhospital.com/healthLib/atoz/cardiac/effects.html. Retrieved 2005.

96.

^ a b Senelick Richard C., Rossi, Peter W.,Dougherty, Karla (1994). Living with Stroke:A Guide for Families. Contemporary Books,Chicago. ISBN 0809226073.OCLC 42835161 40856888 42835161(http://www.worldcat.org/oclc/40856888) .

97.

^ a b Villarosa, Linda, Ed., Singleton,LaFayette, MD, Johnson, Kirk A. (1993).Black Health Library Guide to Stroke. HenryHolt and Company, New York.

98.

^ Reith J, Jørgensen HS, Nakayama H,Raaschou HO, Olsen TS (August 1997)."Seizures in acute stroke: predictors andprognostic significance. The CopenhagenStroke Study" (http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=9259753) . Stroke 28 (8): 1585–9.PMID 9259753(http://www.ncbi.nlm.nih.gov/pubmed/9259753) . http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=9259753.

99.

^ Burn J, Dennis M, Bamford J, SandercockP, Wade D, Warlow C (December 1997)."Epileptic seizures after a first stroke: theOxfordshire Community Stroke Project"(http://bmj.com/cgi/pmidlookup?view=long&pmid=9437276) . BMJ 315 (7122): 1582–7.PMC 2127973(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=2127973) . PMID 9437276(http://www.ncbi.nlm.nih.gov/pubmed/9437276) . http://bmj.com/cgi/pmidlookup?view=long&pmid=9437276.

100.

^ Murray CJ, Lopez AD (1997). "Mortalityby cause for eight regions of the world:

101.

Global Burden of Disease Study". Lancet349 (9061): 1269–76.doi:10.1016/S0140-6736(96)07493-4(http://dx.doi.org/10.1016%2FS0140-6736%2896%2907493-4) . PMID 9142060(http://www.ncbi.nlm.nih.gov/pubmed/9142060) .^ (PDF) The World health report 2004.Annex Table 2: Deaths by cause, sex andmortality stratum in WHO regions, estimatesfor 2002. (http://www.who.int/entity/whr/2004/en/report04_en.pdf) . Geneva:World Health Organization. 2004.http://www.who.int/entity/whr/2004/en/report04_en.pdf.

102.

^ Ellekjær, H; Holmen J, Indredavik B,Terent A (November 1, 1997)."Epidemiology of Stroke in Innherred,Norway, 1994 to 1996 : Incidence and30-Day Case-Fatality Rate"(http://stroke.ahajournals.org/cgi/content/abstract/strokeaha%3B28/11/2180) . Stroke28 (11): 2180–2184. PMID 9368561(http://www.ncbi.nlm.nih.gov/pubmed/9368561) . http://stroke.ahajournals.org/cgi/content/abstract/strokeaha%3B28/11/2180. Retrieved 2008-01-22.

103.

^ Bongers T, de Maat M, van Goor M et al.(2006). "High von Willebrand factor levelsincrease the risk of first ischemic stroke:influence of ADAMTS13, inflammation, andgenetic variability". Stroke 37 (11): 2672–7.doi:10.1161/01.STR.0000244767.39962.f7(http://dx.doi.org/10.1161%2F01.STR.0000244767.39962.f7). PMID 16990571(http://www.ncbi.nlm.nih.gov/pubmed/16990571) .

104.

^ Ashrafian H (2010). "Familial stroke 2700years ago". Stroke 41 (4): e187.doi:10.1161/STROKEAHA.109.573170(http://dx.doi.org/10.1161%2FSTROKEAHA.109.573170) .PMID 20185778(http://www.ncbi.nlm.nih.gov/pubmed/20185778) .

105.

^ a b Thompson JE (August 1, 1996). "Theevolution of surgery for the treatment andprevention of stroke. The Willis Lecture"(http://stroke.ahajournals.org/cgi/content/full/27/8/1427) . Stroke 27 (8): 1427–34.PMID 8711815(http://www.ncbi.nlm.nih.gov/pubmed/8711815) . http://stroke.ahajournals.org/cgi/content/full/27/8/1427.

106.

^ Kopito, Jeff (September 2001). "A Strokein Time" (http://www.webasx.com/articles

107.


30 of 31 13/03/11 10:42 PM

/strokeintime.html) . MERGINET.com 6 (9).http://www.webasx.com/articles/strokeintime.html.^ R. Barnhart, ed. The Barnhart ConciseDictionary of Etymology (1995)

108.

^ Schiller F (April 1970). "Concepts ofstroke before and after Virchow"(http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1034034) . Med Hist 14 (2): 115–31.

109.

PMC 1034034(http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1034034) . PMID 4914683(http://www.ncbi.nlm.nih.gov/pubmed/4914683) .http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1034034.

Further readingJ. P. Mohr, Dennis Choi, James Grotta, Philip Wolf (2004). Stroke: Pathophysiology,Diagnosis, and Management. New York: Churchill Livingstone. ISBN 0-443-06600-0.OCLC 52990861 50477349 52990861 (http://www.worldcat.org/oclc/50477349) .Charles P. Warlow, Jan van Gijn, Martin S. Dennis, Joanna M. Wardlaw, John M.Bamford, Graeme J. Hankey, Peter A. G. Sandercock, Gabriel Rinkel, Peter Langhorne,Cathie Sudlow, Peter Rothwell (2008). Stroke: Practical Management (3rd ed.). Wiley-Blackwell. ISBN 1-4051-2766-X.

Retrieved from "http://en.wikipedia.org/wiki/Stroke"Categories: Stroke | Aging-associated diseases | Cerebrovascular diseases

This page was last modified on 12 March 2011 at 16:59.Text is available under the Creative Commons Attribution-ShareAlike License;additional terms may apply. See Terms of Use for details.Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profitorganization.


31 of 31 13/03/11 10:42 PM

stroke - wikipedia, the free encyclopedia

Documents