STROKEARLYN M. VALENCIA , M.D.Associate Professor, UNSOMDiplomate, American Board Of Psychiatry & Neurology

LEARNING OBJECTIVESTo be able to define stroke, discuss its pathophysiology and risk factorsTo emphasize early evaluation and management of stroke patients To discuss the latest stroke treatment strategiesCASE 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 death750, 000 cases/yearLeading cause of significant disabilityCost: $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 StrokeIschemic, 80% - thrombosis, 50% (small & large-vessel) - embolism, 30% [now believed significantly higher]Hemorrhagic, 20% - intracerebral (HTN as risk) - subarachnoid (aneurysm)

Stroke vs. TIATransient 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)Stroke: Clinical syndrome characterized by an acute 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.

Risk Factors for Stroke That Cannot Be ChangedIncreased 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 PopulationGroups Defined by Race, Age, and Gender: 1993

Risk Factor For Stroke: TreatableMajor Hypertension Heart disease, esp. atrial fibrillation Cigarette smoking Transient ischemic attacksDyslipidemiaPhysical inactivityObesity Less Well DocumentedExcessive alcohol intake / drug abuse Acute infection*

Alcohol Consumption as a Risk Factor for StrokeHeavy 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 StrokeLight 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 DocumentedGeography/climate Socieconomic factors

The Stroke Belt

Potential Genetic Risk Factors for StrokeApolipoprotein E4Elevated homocysteine levelsFactor V mutation

ATHEROSCLEROSIS AND THROMBOSISAtherosclerosis: decades-long process; progression favored by hypercholesterolemia, HTN, cigarette smokingFatty streak: yellowish discoloration on intimal surface of bloodFocal plaques: eccentric thickening at bifurcations; addition of massive extracellular lipids that displaced normal cells and matrixComplicated fibrous plaques: central acellular area of lipid covered by a cap of smooth muscle cells and collagen

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 InjuryFunctional alteration of endothelial cell layerDenuding of endotheliumSuperficial intimal injuryDeep 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 ProliferationAlong with macrophages, smooth-muscle 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 productsPlatelets 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 ThrombusThe 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 FissuringAcute 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 ActivationOn 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

Atherothromboticocclusion of larger arteriesEmbolism: Artery-to artrey, cardiogenicPrimary small vessel disease (lipohyalinosis)

Thromboembolism

Cardiogenic EmboliCardiogenic 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 IschemiaNeuronal Function: Importance of Oxygen and GlucoseThe 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 ProgressesThe duration, severity, and location of focal cerebral ischemia determine the extent of brain function and thus the severity of stroke

Cellular Injury During IschemiaInadequate Energy SupplyLack 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 SignsSudden weakness, paralysis, or numbness of the face, arm and the leg on one or both sides of the bodyLoss of speech, or difficulty speaking or understanding speechDimness or loss of vision, particularly in only one eyeUnexplained dizziness (especially when associated with other neurologic symptoms), unsteadiness, or sudden fallsSudden severe headache and/or loss of consciousness

Left & Right HemisphericStroke: Common PatternsMiddle 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 convolutionsMost frequently affected in embolic & thrombotic stroke

Left and Right Hemisphere Stroke: Common Patterns Left (Dominant) Hemisphere Stroke: Common PatternRight (Non-dominant) Hemisphere Stroke: Common Pattern Aphasia Right hemiparesisRight-sided sensory loss Right visual field defect Poor right conjugate gaze DysarthriaDifficulty reading, writing, or calculating Neglect of left visual field Extinction of left-sided stimuli Left hemiparesisLeft-sided sensory loss Left visual field defect Poor left conjugate gaze DysarthriaSpatial disorientation

Posterior Circulation (Vertebrobasilar Territory) StrokeAtaxia, gait abnormalitiesDiplopia, oscillopsia, nystagmus, dysconjugate eye movementsNausea & vomiting (center is in area post-rema)Crossed hemiparesis, hemisensory deficitsHeadache more common

Differential Diagnosis of StrokeCraniocerebral / cervical traumaMeningitis/encephalitisIntracranial massTumor Subdural hematoma Seizure with persistent neurological signsMigraine with persistent neurological signsMetabolicHyperglycemia Hypoglycemia Post-cardiac arrest ischemia Drug/narcotic overdose

AHA Stroke Council Recommended Assessment of a Person with Suspected StrokeEMS 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 StrokeEMS 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-UPHistory and PEComputed Tomography (CT) scan of the head12-lead EKG, chest X-rayComplete blood count, PT, PTTChemistries (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-rayArterial blood gasLumbar punctureElectroencephalogram (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 AngiographySingle Photon Emission Computed Tomography (SPECT) 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 PATIENTMaintenance of adequate tissue oxygenation: protecting the airway, O2 inhalationMaintaining optimal blood pressure (autoregulation faulty or lost in stroke patients)

STROKE MANAGEMENT

EMERGENT SUPPORTIVE CARE OF ACUTE STROKE PATIENTManagement of blood glucose abnormalities (hyperglycemia associated with poorer prognosis)Management of fever and infections (ischemia worsened by hyperthermia, improved by hypothermia

ACUTE SROKE CARE 2007: Therapies with FDA Approval or Positive Trials For Ischemic StrokeIV TPA (< 3hours) IA fibrinolysis (< 6 hours) IA MERCI retriever < 8 hours Endovascular temperature control

Acute Stroke TreatmentIntravenous recombinant tissue plasminogen activator (TPA): within 3 hours of stroke symptom onsetIntraarterial 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 ProgressionHypotensionHyperglycemiaHyperthermiaInfectionCerebral hypoperfusion

Brain Edema

TREATMENT OF BRAIN SWELLINGCerebral perfusion pressure =MAP-ICPFluid Restriction (1200 ml /day/m2)Controlled hyperventilation: 25 mm HgMannitol, 0.25 mg/kg IV over 20 minutes; repeat PRN, serum osmolality maintained in the range of 300-320mOsm/lBarbiturate coma, with ICP monitoring (subarachnoid bolt, IV catheter or Camino catheter): maintain CPP greater than 50 mmHg; pentobarbital serum level of 2-4 mg/dlSurgery (wait 2 weeks)

Management of Cerebral Edema, Increased Intracranial Pressure and HydrocephalusBrain edema peaks at 3-5 daysTreatment includes: 1. hyperventilation (lower PCO2) 2. osmotic diuretics 3. drainage of CSF (ventriculostomy) 4. surgery (lobectomy)

Neuroprotective AgentsSeveral trials going onSo far, trial on one free-radical scavenger showed positive resultsPhase II trials have proven beneficial; Phase III (human efficacy trials) non-benefial to negativeCommon measures may “neuroprotect”

Stroke PreventionAnticoagulants (Heparin, Warfarin)Antiplatelets (aspirin, clopidogreldipyridamole/ASA combination, ticlopidine)StatinARB (-sartan), or ACE inhibitor + HCTZCarotid endarterectomy if indicatedCarotid 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!