STROKE

ARLYN M. VALENCIA , M.D.

Associate Professor, UNSOM Diplomate, American Board Of Psychiatry & Neurology

LEARNING OBJECTIVES
To be able to define stroke, discuss its pathophysiology and risk factors

To emphasize early evaluation and management of stroke patients

To discuss the latest stroke treatment strategies CASE STUDIES: To be able to analyze clinical situations, localize the stroke lesion, determine

probable etiology

THE BRAIN IS A VERY UNIQUE, HIGH-MAINTENANCE END- ORGAN. IT IS VERY DEPENDENT ON MOMENT-TO-MOMENT SUPPLY OF GLUCOSE AND OXYGEN TO SUSTAIN ITS HIGH-POWERED ACTIVITIES. IT IS VERY SENSITIVE TO THE SYSTEMIC STATE. ANY SEVERE MEDICAL INSULT, THEREBY, HAS TREMENDOUS IMPACT ON THE BRAIN METABOLISM. ANY MEDICAL EMERGENCY IS A NEUROLOGIC EMERGENCY!
A. Valencia, M.D.

The biology of stroke is such that each moment of ischemia and tissue injury increases the degree of irreversible tissue damage.

CEREBROVASCULAR ACCIDENT OR BRAIN ATTACK

Third leading cause of death 750, 000 cases/year Leading cause of significant disability Cost: $40 billion/year

Major Causes of Death in the United Sates, 1995

Annual Economic Costs of Stroke (All Types) In The US

Death Rates for Stroke per 100,000 Population

Types of Stroke
Ischemic, 80%

- thrombosis, 50% (small & large-vessel) - embolism, 30% [now believed significantly higher] Hemorrhagic, 20% - intracerebral (HTN as risk) - subarachnoid (aneurysm)

Stroke vs. TIA

Transient ischemic attack (TIA): A clinical

syndrome characterized by an acute loss of focal brain or monocular function with symptoms lasting less than 24 hrs and which is thought to be due to inadequate cerebral or ocular blood supply, without ischemic changes in Diffusion Weighted Imaging (DWI) loss of focal brain or monocular function with symptoms lasting greater than 24 hrs and which is thought to be due to inadequate cerebral or ocular blood supply.

Stroke: Clinical syndrome characterized by an acute

Risk Factors for Stroke That Cannot Be Changed

Increased age Being male Race (e.g., African-Americans) Diabetes mellitus Prior stroke/transient ischemic attacks Family history of stroke Asymptomatic carotid bruit

Up to approximately 30% of people who suffer transient attacks (TIAs) will develop a stroke within 5 years.

Relative Incidence of Atherothrombotic Stroke and MI by Age and Gender

Death Rates for Stroke per 100,000 Population Groups Defined by Race, Age, and Gender: 1993

Risk Factor For Stroke: Treatable

Major
Hypertension Heart disease, esp. atrial fibrillation Cigarette smoking Transient ischemic attacks Dyslipidemia Physical inactivity Obesity

Less Well Documented

Excessive alcohol intake / drug abuse Acute infection*

Alcohol Consumption as a Risk Factor for Stroke

Heavy alcohol consumption may increase risk

of stroke by a number of mechanisms. The reported effects of alcohol consumption on risk of ischemic stroke have been inconsistent. A differential effect of alcohol consumption on stroke risk in men compared to women has been observed.

Alcohol Consumption as a Risk Factor for Stroke

Light and moderate alcohol use tend to raise levels of high-density-lipoprotein (HDL) -- the

"good" lipoprotein. Heavy drinking or binge drinking, is related to an increased incidence of stroke as a cause of death Light or moderate alcohol consumption, is related to a reduced risk of coronary heart disease. There is positive, dose-related effect of alcohol consumption on risk of intracranial hemorrhage, both arachnoid and intracerebral .

Less Well Documented

Geography/climate Socieconomic factors

The Stroke Belt

Potential Genetic Risk Factors for Stroke

Apolipoprotein E4

Elevated homocysteine levels

Factor V mutation

ATHEROSCLEROSIS AND THROMBOSIS

Atherosclerosis: decades-long process; progression favored by hypercholesterolemia, HTN, cigarette smoking Fatty streak: yellowish discoloration on intimal surface of blood

Focal plaques: eccentric thickening at bifurcations; addition of massive extracellular lipids that displaced normal cells and matrix
Complicated fibrous plaques: central acellular area of lipid covered by a cap of smooth muscle cells and collagen

Atherosclerosis and Thrombus Formation: Arterial Wall Injury

Functional alteration of

endothelial cell layer

Denuding of endothelium Superficial intimal injury

Deep intimal & media

damage with marked platelet aggregatio and mural thrombosis

Role of Monocytes and T-Lymphocytes in the Transformation to Foam Cells

Oxidation of LDL-Cholesterol

Oxidized LDL-cholesterol Contributes To Atherogenesis In Three Other Ways:

It has cytotoxic properties that may promote endothelial injury; It acts as a chemoattractant for circulating monocytes, leading to their increased accumulation with plaques; and Inhibits egress of macrophages from plaques.

Smooth Muscle Cell Migration and Proliferation

Smooth Muscle Cell Migration and Proliferation

Along with macrophages, smoothmuscle cells proliferate in the intima during atherogenesis.
Smooth muscle cell layer makes up a substantial bulk of the atherosclerotic lesion, which may rise several millimeters above the surface of the surrounding intima

Role of Platelets

Platelet adhesion may be

promoted by type II injury and by toxic products Platelets release growth factors that stimulate SM migration and proliferation and formation of fibrointimal lesions and the outside capsule of fatty lesions

Plaque Fissuring and Formation of Platelet Thrombus

The vulnerability of such a

structure to fissuring appears to be related to circumferential stress on the plaque cap in systole, as well as infiltration of the cap tissue with foam cells (with reduction of total collagen content and a concomitant fall in tensile strength)

Potential Outcomes of Plaque Fissuring

Acute episodes of transient ischemia and ischemic stroke (as well

as myocardial infarction, unstable angina, as sudden death) may be precipitated by thrombosis on atherosclerotic plaques.

Thrombus Formation I -- Platelet Activation

On contact with collagen, platelets become activated, with platelet adhesion, secretion of platelet contents, and platelet aggregation at the site of injury. The activated platelet surface is an essential catalytic surface for several coagulation reactions that generate thrombin, a key factor in the coagulation sequence

Thrombus Formation II -- Platelet Activation and Blood Flow

Thrombus Formation III -- Activation of Coagulation Cascade

Evolution of Cerebral Atherothrombosis

 Atherothrombotic occlusion of

larger arteries
Embolism: Artery-to artrey,

cardiogenic
Primary small vessel disease

(lipohyalinosis)

Thromboembolism

Cardiogenic Emboli
Cardiogenic

emboli lodge in the middle cerebral artery or its branches in 80% of cases, in the posterior cerebral artery or its branches 10% of the time, and in the vertebral artery or its branches in the remaining 10% of cases.

Major Blood Vessels Of The Brain

Major Blood Vessels Of The Brain

Control Centers of the Brain

Cellular Injury During Ischemia Neuronal Function: Importance of Oxygen and Glucose

The transient change in

voltage induced by the action potential is determined by the concentration of ions on either side of the cell membrane. Maintaining these ionic gradients is an energy-consuming process that requires a constant supply of glucose and oxygen to the neuron.

Cellular Changes As Ischemia Progresses

The duration, severity, and location of focal cerebral ischemia determine the extent of brain function and thus the severity of stroke

Cellular Injury During Ischemia Inadequate Energy Supply

Lack of glucose and oxygen deplete the cellular energy stores required to maintain electrical potentials and ion gradients. The membrane that surrounds each affected neuron becomes "leaky," and the cell loses potassium and adenosine triphosphate (ATP), the tissue's medium for energy exchange

THE ISCHEMIC PENUMBRA

Stroke Warning Signs

Sudden weakness, paralysis, or numbness of the face, arm

and the leg on one or both sides of the body speech

Loss of speech, or difficulty speaking or understanding

Dimness or loss of vision, particularly in only one eye Unexplained dizziness (especially when associated with Sudden severe headache and/or loss of consciousness

other neurologic symptoms), unsteadiness, or sudden falls

Left & Right Hemispheric Stroke: Common Patterns

Middle Cerebral Artery (MCA): supplies the

lateral surface of hemisphere except for: 1. frontal lobe 2. strip along superomedial border of frontal lobe 3. lowest temporal convolutions Most frequently affected in embolic & thrombotic stroke

Left and Right Hemisphere Stroke: Common Patterns

Left (Dominant) Hemisphere Stroke: Common Pattern

Right (Non-dominant) Hemisphere Stroke: Common Pattern

Aphasia
Right hemiparesis Right-sided sensory loss

Neglect of left visual field Extinction of left-sided

Right visual field defect

Poor right conjugate gaze Dysarthria Difficulty reading, writing,

or calculating

stimuli Left hemiparesis Left-sided sensory loss Left visual field defect Poor left conjugate gaze Dysarthria Spatial disorientation

Posterior Circulation (Vertebrobasilar Territory) Stroke

Ataxia, gait abnormalities Diplopia, oscillopsia, nystagmus,

dysconjugate eye movements Nausea & vomiting (center is in area postrema) Crossed hemiparesis, hemisensory deficits Headache more common

Differential Diagnosis of Stroke

Craniocerebral / cervical trauma Meningitis/encephalitis Intracranial mass
Tumor Subdural hematoma

Seizure with persistent neurological signs

Migraine with persistent neurological signs Metabolic
Hyperglycemia

Hypoglycemia
Post-cardiac arrest ischemia Drug/narcotic overdose

AHA Stroke Council Recommended Assessment of a Person with Suspected Stroke

EMS should be instructed in the rapid recognition,

evaluation, treatment and transport Baseline assessment within minutes, CT scan ASAP; use National Institutes of Health Stroke Scale (NIHSS)

AHA Stroke Council Recommended Assessment of a Person with Suspected Stroke

EMS should be instructed in the rapid recognition,

evaluation, treatment and transport Baseline assessment within minutes, CT scan ASAP; use National Institutes of Health Stroke Scale (NIHSS)
Immediate evaluation of the following:

1. Airway 2. Vital signs 3. General medical assessment (including evidence of injury, cardiovascular abnormalities) 4. Neurological assessment (frequent)

EVALUATION AND WORK-UP

History and PE Computed Tomography (CT) scan of the

head 12-lead EKG, chest X-ray Complete blood count, PT, PTT Chemistries (sodium, phosphate, glucose abnormalities may mimic stroke) Urine and serum toxicology (drugs and alcohol)

Under special circumstances, the following tests may be required:

Cervical spine x-ray Arterial blood gas Lumbar puncture Electroencephalogram (EEG)

Other Neuroimaging Techniques & Ancillary Tests

Magnetic Resonance Imaging (MRI)

Diffusion Weighted Imaging (DWI),

Magnetic Resonance Angiography (MRA)
Ultrasound

(Carotid Duplex, Transcranial Doppler, 2-D echo) Conventional Angiography Tomography (SPECT)

Single Photon Emission Computed

Positron Emission Tomography

Computed Tomography

Carotid Duplex

Transcranial Doppler

Cerebral Angiography

 Functional abnormality demonstrated with PET exceeds that seen with structural imaging techniques such as X-

ray, CT, or MRI and is more representative depiction of the underlying functional state of the brain.

SPECT and Xenon Contrast CT

EMERGENT SUPPORTIVE CARE OF ACUTE STROKE PATIENT

Maintenance of adequate tissue oxygenation:

protecting the airway, O2 inhalation Maintaining optimal blood pressure (autoregulation faulty or lost in stroke patients)

STROKE MANAGEMENT

EMERGENT SUPPORTIVE CARE OF ACUTE STROKE PATIENT

Management of blood glucose abnormalities

(hyperglycemia associated with poorer prognosis) Management of fever and infections (ischemia worsened by hyperthermia, improved by hypothermia

 IV TPA (< 3hours) IA fibrinolysis (< 6 hours) IA MERCI retriever < 8 hours Endovascular temperature control

Acute Stroke Treatment

Intravenous recombinant tissue plasminogen activator (TPA): within 3 hours of stroke

symptom onset Intraarterial TPA: within 6 hours; MCA territory stroke by angiography

The Merci Retrieval System

Hypothermia For Acute Stroke: Intravascular Cooling

Physiologic Effects Of Various Levels Of Hypothermia

Known Factors That Cause Stroke Progression

Hypotension Hyperglycemia Hyperthermia Infection Cerebral hypoperfusion

Brain Edema

TREATMENT OF BRAIN SWELLING

Cerebral perfusion pressure =MAP-ICP
Fluid Restriction (1200 ml /day/m2) Controlled hyperventilation: 25 mm Hg Mannitol, 0.25 mg/kg IV over 20 minutes; repeat PRN, serum osmolality maintained in the range of 300-320mOsm/l Barbiturate coma, with ICP monitoring

(subarachnoid bolt, IV catheter or Camino catheter): maintain CPP greater than 50 mmHg; pentobarbital serum level of 2-4 mg/dl Surgery (wait 2 weeks)

Management of Cerebral Edema, Increased Intracranial Pressure and Hydrocephalus

Brain edema peaks at 3-5 days Treatment includes: 1. hyperventilation (lower PCO2) 2. osmotic diuretics 3. drainage of CSF (ventriculostomy) 4. surgery (lobectomy)

Neuroprotective Agents
Several trials going on So far, trial on one free-radical scavenger

showed positive results Phase II trials have proven beneficial; Phase III (human efficacy trials) non-benefial to negative Common measures may neuroprotect

Stroke Prevention
Anticoagulants (Heparin, Warfarin) Antiplatelets (aspirin, clopidogrel

dipyridamole/ASA combination, ticlopidine) Statin ARB (-sartan), or ACE inhibitor + HCTZ Carotid endarterectomy if indicated Carotid or intracranial stent. Risk factor control!!!

Concept of Stroke Teams & Stroke Units

Time is brain

Stroke awareness
Common mistakes may

lead to fatal consequences Boutique stroke neurology: Patients will receive best care; length of stay shortened

THANK YOU!