Ischemic Stroke

ischemic stroke:

An episode of neurological dysfunction caused by focal cerebral infarction.

CNS infarction is brain cell death attributable to ischemia, based on

1. pathological, imaging, or other objective evidence of cerebral focal ischemic injury in a defined vascular distribution

2. clinical evidence of cerebral focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded.

Subtypes of Ischemic Stroke

• large artery thrombosis

• lacunar stroke (small vessel)

• cardiogenic embolic stroke

• cryptogenic stroke

Large artery thrombosis

is the formation of a blood clot within a major artery, leading to the partial or complete obstruction of blood flow, which can result in ischemic damage to the organs or tissues supplied by that artery.

Lacunar stroke (small vessel)

is an ischemic stroke caused by the occlusion of small, penetrating arteries in the brain, resulting in a small, localized infarct within deep brain structures, often linked to chronic hypertension and diabetes.

Cardiogenic embolic stroke

is an ischemic stroke caused by a blood clot that originates in the heart and embolizes to the brain, resulting in the obstruction of a cerebral artery and subsequent brain tissue damage.

Cryptogenic stroke

is an ischemic stroke for which no specific cause can be identified after a thorough diagnostic workup, including the exclusion of known stroke etiologies like large artery atherosclerosis, cardioembolism, and small vessel disease.

types of ischemic stroke

• cryptogenic

• cardiogenic embolic

• small penetrating artery thrombosis (lacunar stroke)

• large artery thrombosis (atherosclerotic disease)

Large Arteries Involved:

The stroke involves major arteries supplying blood to extensive regions of the brain. Common arteries affected include the internal carotid artery, middle cerebral artery, vertebral artery, and basilar artery.

Formation of Thrombus:

The clot that causes the blockage usually forms at the site of an atherosclerotic plaque within the artery. Atherosclerosis, or the buildup of fatty deposits along the arterial walls, is the primary underlying condition leading to thrombus formation.

Sudden Onset of Symptoms:

Symptoms of large vessel thrombotic stroke often appear suddenly and can include paralysis (often on one side of the body), difficulty speaking or understanding speech, vision problems, dizziness, and loss of coordination. The specific symptoms depend on the artery involved and the area of the brain it supplies.

Severe Outcomes:

Because these strokes affect large portions of the brain, they can be particularly devastating, leading to significant neurological deficits, long-term disability, or death if not treated promptly.

large artery thrombosis

atherosclerosis and thrombus

Atherosclerosis

• type of arteriosclerosis.

• Atherosclerosis causes arteries to narrow, weaken and be less flexible. It's the term for the process of fatty buildup in the inner lining of an artery.

• The buildup that results is called plaque and reduces the amount of blood and oxygen that is delivered to vital organs.

Small vessel lacunar infarct

is an ischemic stroke caused by the occlusion of small, penetrating arteries in the brain, resulting in a small, localized infarct within deep brain structures, often linked to chronic hypertension and diabetes

Lacunar Stroke - size

small size - Lacunar strokes are typically small, usually less than 15 mm in diameter.

Lacunar Stroke - Location:

They occur in subcortical areas, affecting deep brain structures like the basal ganglia, internal capsule, thalamus, and pons.

Lacunar Stroke - Causes:

The most common cause is small vessel disease, often associated with hypertension and diabetes.

Lacunar Stroke - Symptoms:

Depending on the location, symptoms can include motor or sensory deficits, but they usually do not involve higher cognitive functions or consciousness. Common syndromes include pure motor stroke, pure sensory stroke, and sensorimotor stroke.

Lacunar Stroke - Prognosis:

Lacunar strokes often have a better prognosis than other types of strokes because they generally affect smaller areas of the brain, though they can lead to cumulative damage over time if multiple strokes occur

Hypertension and lacunar stroke

• Hypertension, or high blood pressure, is a major risk factor for lacunar stroke due to its damaging effects on the small blood vessels in the brain. hypertension contributes to the development of lacunar strokes because of

  • Lumen narrowing

  • Lipohyalinosis

  • Microatheromas

  • Artherosclerosis

Cardiogenic embolic stroke

is an ischemic stroke caused by a blood clot that originates in the heart and embolizes to the brain, resulting in the obstruction of a cerebral artery and subsequent brain tissue damage.

Origin of Embolus:

The clot (embolus) originates in the heart, typically in conditions where the heart is prone to forming clots. Common sources include:

• atrial fibrillation

• heart valve disease

• endocarditis

• cardiomyopathy

Atrial Fibrillation (AFib):

An irregular heartbeat that leads to blood pooling and clot formation in the atria.

Heart Valve Disease:

Particularly with artificial valves or damaged natural valves.

Myocardial Infarction (Heart Attack):

Can lead to areas of the heart that do not contract properly, increasing clot risk.

Endocarditis:

Infection of the heart valves or lining, which can cause clots or pieces of infected tissue to break off and travel to the brain.

Cardiomyopathy:

Diseases of the heart muscle that reduce its ability to pump effectively, leading to clot formation.

Cardiogenic embolic strokes - Sudden and Severe Symptoms:

often occur suddenly and result in severe neurological symptoms, such as paralysis, loss of speech, or vision problems, depending on where the embolus lodges in the brain.

Cardiogenic embolic strokes - Recurrent Risk:

There is a high risk of recurrent strokes if the underlying heart condition is not treated or controlled. Multiple emboli can be generated, leading to recurrent strokes.

Cerebral embolism

A sudden block of a artery or vein by a clot or other substance (fat, air, bacteria, foreign body) that was brought to its place by the blood flow

Cryptogenic stroke

is an ischemic stroke for which no specific cause can be identified after a thorough diagnostic workup, including the exclusion of known stroke etiologies like large artery atherosclerosis, cardioembolism, and small vessel disease.

Extensive Evaluation: Cryptogenic strokes are diagnosed after a thorough evaluation, which typically includes:

• Brain imaging (e.g., MRI or CT scan) to confirm the presence of a stroke.

• Vascular imaging (e.g., ultrasound, MR angiography) to check for large vessel disease.

• Cardiac monitoring (e.g., echocardiogram, prolonged Holter monitoring) to detect potential sources of emboli, such as atrial fibrillation or structural heart disease.

• Blood tests to rule out clotting disorders or other systemic conditions.

Cryptogenic strokes - Potential Underlying Causes: Even though a specific cause is not identified, several potential mechanisms may still be suspected:

• Paroxysmal Atrial Fibrillation (AFib): Intermittent AFib may go undetected during short-term monitoring but could still be the source of embolic strokes.

• Patent Foramen Ovale (PFO): A small hole in the heart that did not close after birth may allow clots to pass from the venous to the arterial circulation, leading to a stroke.

• Undetected Atherosclerosis: Small, unrecognized plaques in the arteries may be missed on imaging but still pose a risk.

• Prothrombotic States: Conditions that increase the likelihood of clot formation but are not identified through routine blood tests.

Paroxysmal Atrial Fibrillation (AFib):

Intermittent AFib may go undetected during short-term monitoring but could still be the source of embolic strokes.

Patent Foramen Ovale (PFO):

A small hole in the heart that did not close after birth may allow clots to pass from the venous to the arterial circulation, leading to a stroke.

Undetected Atherosclerosis:

Small, unrecognized plaques in the arteries may be missed on imaging but still pose a risk.

Prothrombotic States:

Conditions that increase the likelihood of clot formation but are not identified through routine blood tests.

TOAST

is a commonly used classification system that categorizes ischemic strokes according to their underlying cause (etiology).

Classification of Subtype of Acute Ischemic Stroke - TOAST

• This is organization was developed in 1993 for the Trial of Org10172 for acute stroke treatment (TOAST) clinical trial.

• 5 subtypes

  • Large vessel artherosclerosis

  • Cardioembolism

  • Small vessel occlusion

  • Stroke of other determined etiologies (cryptogenic)

  • Stroke of undetermined etiologies

• ASCO phenotyping: A-atherosclerosis, S: small vessel disease, C: cardioembolism, O: other causes.

• ASCOD: added D: dissection

TIA= Transient ischemic attack

• often referred to as a "mini-stroke," is a temporary period of neurological dysfunction caused by a brief interruption in blood supply to part of the brain. Unlike a full stroke, the blockage in a TIA is temporary, and blood flow resumes, typically without causing permanent damage.

• Time is NOT a primary distinguishing factor between stroke and TIA. Time should be a secondary consideration when adequate imaging is unavailable.

Risk of Stroke following TIA

• FACT: Up to 40 percent of all people who experience a TIA will go on to have an actual stroke.

• FACT: Within two days after a TIA, 5 percent of people will have a stroke.

• FACT: Within three months after a TIA, 10 to 15 percent of people will have a stroke

Ischemic Core and Penumbra

• The core ischemic zone (blood flow < 10-25%)

• The ischemic penumbra- this is the area between brain tissue receiving normal blood flow and the ischemic zone- it is the area that surrounds the ischemic zone. This region remains viable for several hours following a stroke, however, if circulation is not re-established cells in this region will also die.

Stroke Risk Factors

Modifiable

• hypertension, diabetes mellitus, atrial fibrillation, dyslipidemia, smoking tobacco, sedentary lifestyle, kidney disease, sleep apnea, heavy alcohol intake, diet

nonmodifiable

• male sex, genetic susceptibility, age

Symptoms seen during TIA’s and Acute Stroke

symptoms can appear separately, in combination or with FAST signs

1. sudden confusion, trouble speaking or understanding speech

2. sudden numbness or weakness of face, arm or leg. especially on one side of the body

3. sudden trouble seeing in one or both eyes

4. sudden trouble walking, dizziness, loss of balance or coordination

5. sudden severe headache with no known cause

THESE ARE WARNING SIGNS OF STROKE

Clinical Presentation

• The clinical presentation of an ischemic stroke typically involves a sudden onset of neurological symptoms due to the interruption of blood flow to a part of the brain.

• The specific symptoms depend on the area of the brain affected.

American Heart Association Position

• There should be no difference in response to a TIA or a stroke. Although a TIA resolves itself before there is damage, there is no way to predict which clots will dissolve on their own.

• Stroke — and TIA — are medical emergencies; dial 9-1-1 and tell the operator you think it’s a stroke and note the time the symptoms started.

• Remember: Time lost is brain lost.

Management of an Acute Ischemic Stroke

• Brain Attack – Call 911

• Time is Brain

• High priority- for early medical care

• Stroke protocols/ Clinical Pathways

What to expect at the hospital

• Arrival at the Hospital: Detailed medical history and information about any past medical conditions. Knowing the exact time stroke symptoms began is most helpful to initiate intervention immediately!!

• Initial Tests: Rule out any other conditions that have symptoms similar to a stroke.

• Diagnostic tests: Lab work, CT scan/MRI, etc..

• Begin Treatment following Acute Stroke Protocols

CBC - Complete Blood Count

Looks at RBC, WBC, platelets, r/o anemia, infection…

Coagulation test

INR (International normalized ratio)

• Norm without medication .8-1.2

• Norm with medication 2-3

• If too high → risk of bleed

• If too low → risk of clot

Blood chemistry

• Glucose

  • If too high or too low can mimic stroke sx

  • Fasting glucose level dx DM a risk factor in stroke

• Serum electrolytes

  • Sodium, potassium, calcium

• Blood lipid test

  • Cholesterol, total lipids, HDL, LDL

• Toxicity screen

• Others

  • Syphilis (related to arteritis)

  • Cardiac enzymes

  • Coagulation factors

  • Sedimentation rate

Glucose

If too high or too low can mimic stroke sx

Fasting glucose level dx DM a risk factor in stroke

Urinalysis

Renal damage

BUN

Blood urea nitrogen

Usually elevated in pre-renal problems such as in dehydration and renal disease

Imaging

• CT SCAN

• MRI

• Angiography

• Magnetic Resonance Angiogram

• Doppler Ultrasound

• Cardiac evaluation

• Chest XRAY

CT SCAN

• X-rays from different angles-computer makes an image of the cross sections of the brain

• Shows: soft tissues, bones, blood vessels, tumors- in stroke will see a bleed

• Does it diagnose an acute stroke? The stroke may be too small or not visualized well or it may take several hrs. to show up on CT

• Time – much longer

MRI SCAN

• Machine creates a magnetic field which briefly alters the H2O molecules in the brain cells. The response to this magnetic field is detected and used to create an image of the brain

• Great detail

• Especially of soft tissue

• Views are coronal, sag, axial

• Time 30-90 min

Cerebral Angiography

Image of blood vessels

• A catheter is inserted into the body and dye is injected. Then x-ray or MRI view are taken

• Detects narrowing/blockage of blood vessels

• Risk

  • Invasive

  • Break off plaque

MRA (Magnetic Resonance Angiogram)

• ses MRI to examine blood vessels

• Magnetic resonance angiography – also called a magnetic resonance angiogram or MRA – is a type of MRI that looks specifically at the body’s blood vessels.

• Unlike a traditional angiogram, which requires inserting a catheter into the body, magnetic resonance angiography is a far less invasive and less painful procedure.

Carotid Ultrasound- Doppler

• Test blood flow of carotid arteries

• Uses US waves to image the arteries

• Non-invasive

• Can view and hear sounds of blood flow

  • Carotid doppler

  • Transcranial doppler

Echocardiogram:

TTE= transthoracic echo ; TEE= transesophageal echo

• US waves used to take picture of the heart and its circulating blood

• TTE- US probe placed on the chest

• TEE-US probe placed deep in throat to take picture from the inside

Diagnostic Tests

• Cardiac evaluation- Electrocardiogram-EKG

• Ophthalmic exam

  • See vessel changes in persons with HTN,DM…

• Bruits

• Thyroid Function Test

  • Hypothyroid is associated with accelerated atherosclerosis and elevated cholesterol

Cardiac evaluation-

Electrocardiogram-EKG

Ophthalmic exam

See vessel changes in persons with HTN,DM…

Thyroid Function Test

Hypothyroid is associated with accelerated atherosclerosis and elevated cholesterol

Management of an Acute Ischemic Stroke

• Goal: prevent ischemic cascade cell death

• Acute Interventions May include:

  • IV using Thrombolytic medication (tPA)

  • Intra atrial tPA

  • Endovascular Procedures such as Clot Retrieval systems

• But need to act FAST

Thrombolytic (fibrinolytic) Drugs

re-establish blood flow to the brain by dissolving the clots that are blocking blood flow. In June 1996, the “clot-buster” Activase® became the first acute ischemic stroke treatment to be approved by the Federal Food and Drug Administration (FDA). Activase is also known as tissue plasminogen activator (tPA). To be effective, thrombolytic therapy should be given as quickly as possible.

management of acute stroke

Tissue plasminogen activator (tPA)

• Approved by FDA June 1996

• Tissue plasminogen activator is an enzyme found naturally in the body that converts, or activates, plasminogen into another enzyme to dissolve a blood clot.

• tPA is administered over 60 minutes via IV with 10% of the drug given over 1 minute via a bolus.

• tPA should be given within three hours of the time symptoms first started. Time is an important factor associated with determining whether a patient can receive tPA.

Tissue plasminogen activator (tPA)

Journal of the Stroke: American Heart Association 2009

• Increased window for use of tPA 3 → 4.5 hours

• However, The quicker tPA is given the better results

• Goal is the be transported to the ER ASAP following onset of stroke symptoms  act FAST

• Door to needle time goal is 1 hour or sooner

Benefits of tPA

• Decreased neurological insult

• Improved functional outcomes

• Higher Quality of Life

• Decreased overall healthcare cost

Risk of tPA

Intracranial hemorrhage

Possible re-occlusion

clot retrieval system

• merci retrieval system

• penumbra system

The Merci® Retrieval System

was approved by the FDA in 2004 for patients who are ineligible for IV-tPA or fail to respond to IV-tPA. The system can be used for patients who are beyond the three-hour window for IV-tPA and does not have a time limit for its intended use. The system is a tiny corkscrew-shaped device that works by wrapping around the clot and trapping it. The clot is then retrieved and removed from the body.

The Penumbra System

became available in 2008. It helps safely restore blood flow in or around blocked blood vessels after an ischemic stroke.

Management of an Acute Ischemic Stroke - Overarching Principls

• Reduce damage to ischemic area

• Other Medications used: aimed at

  • Calcium antagonist

  • Glutamate antagonist

  • Neuroprotective agents

• Maintain circulation of O2

• Maintain BP

• Mild sedation

• Manage cardiac arrhythmia

• Manage blood sugar levels

• Watch for intracerebral edema and ICP

• Watch for seizure

• ICU: Monitor- cardiopulmonary status

Stroke Management - General Principles

Goal: Prevent Primary and Secondary Stroke (and/or MI)

Treatment

• Decrease risk factors

• Medical Management

  • Antiplatelet

  • Anticoagulant

• Surgical Management

Stroke Prevention Guidelines: Decrease Risk Factors

Life’s essential 8 are

1. not-smoking

2. physical activity

3. healthy diet

4. body weight

5. sleep health

6. control of cholesterol

7. control of blood pressure

8. control of blood sugar

Carotid endarterectomy

is a surgical procedure designed to reduce the risk of stroke by correcting stenosis (narrowing) of the common carotid artery. Narrowing of these arteries is often due to atherosclerosis, where fatty deposits (plaques) build up and obstruct blood flow

Carotid Endarterectomy - Indications:

• Significant Carotid Artery Stenosis: Usually 70% or more narrowing of the artery.

• Symptoms: Such as transient ischemic attacks (TIAs) or minor strokes

• Asymptomatic Stenosis: severe stenosis (narrowing > 90%) but has not yet experienced symptoms

Carotid Endarterectomy - Significant Carotid Artery Stenosis:

Usually 70% or more narrowing of the artery.

Carotid Endarterectomy - Symptoms:

Such as transient ischemic attacks (TIAs) or minor strokes

Carotid Endarterectomy - Asymptomatic Stenosis:

severe stenosis (narrowing > 90%) but has not yet experienced symptoms

Carotid Endarterectomy - Benefits:

• Stroke Prevention: reduces the risk of future strokes, Risk of stroke <2%

• Symptom Relief: For symptomatic patients, it can alleviate symptoms such as transient ischemic attacks.

Carotid Endarterectomy - Risks:

Stroke: Though rare, there is a small risk of stroke during or immediately after the procedure.

Carotid stenting

is a minimally invasive procedure used to treat carotid artery stenosis, which is the narrowing of the common carotid artery due to atherosclerosis (the buildup of fatty deposits). This procedure involves placing a stent—a small, mesh-like tube—inside the carotid artery to keep it open and improve blood flow to the brain.

Carotid stenting - Indications:

• Significant Carotid Artery Stenosis: Usually 70% or more narrowing of the artery.

• Symptoms: Such as transient ischemic attacks (TIAs) or minor strokes.

• High Surgical Risk: Patients who are at higher risk for complications from carotid endarterectomy due to other medical conditions or anatomical factors.

Carotid stenting - Benefits:

Minimally Invasive, Stroke Prevention

Carotid stenting - Risks:

• Stroke: risk of stroke during or after the procedure, though it is generally lower compared carotid endarterectomy.

• Restenosis: There is a possibility of the artery becoming narrowed again over time.

• Complications: bleeding, infection, or reactions to the contrast dye used during imaging.

Stroke and Evidence-based therapy

Once a known stroke etiology has been established, evidence-based therapy can be instituted to prevent recurrent stroke

• A determination that a stroke was caused by atrial fibrillation (AF) should generally lead to initiation of anticoagulant therapy, which has been shown in clinical trials to be more effective than aspirin for preventing recurrent stroke.

• Identification of cervical carotid artery stenosis proximal to a symptomatic brain infarct should generally lead to carotid revascularization, which has been proven more effective than medical therapy alone in clinical trials.

• If a stroke is classified as resulting from small vessel occlusion, it may be reasonable to aim for a lower-than-usual blood pressure target of less than 130/80 mm Hg.

Evolving Concept of Cryptogenic stroke

Cryptogenic stroke represents a major knowledge gap and therapeutic target in vascular neurology. About one-sixth to one-fourth of ischemic strokes do not have a determined etiology after standard evaluation. Specific strategies for secondary prevention in this group are lacking, but progress has been made over the past decade.