1

Management of Acute

Ischemic Stroke Patients

Jiann-Shing Jeng, MD, PhD

Stroke Center & Department of Neurology

National Taiwan University Hospital, Taipei, Taiwan

2

Stroke Types: NTUH, 1995~2007

Large arteryatherosclerosis

12% Small artery lacune22%

Cardioembolism14%

Other determined4%Undetermined

20%

Cerebralhemorrhage

22%

Subarachnoidhemorrhage

6%

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Stroke Chain of Survival

Detection Recognition of stroke signs/symptoms

Dispatch Call 119 and priority EMS dispatch

Delivery Prompt transport and prehospital notification to hospital

Door Immediate ED triage

Data ED evaluation, prompt laboratory studies, and CT imaging

Decision Diagnosis and decision about appropriate therapy

Drug Administration of appropriate drugs or other intervention

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EMS in Acute Stroke

Rapid identification of acute stroke

Elimination of comorbid conditions mimicking stroke

Stabilization

Rapid transportation

Notification of receiving institution

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Prehospital Stroke Identification

Los Angeles Prehospital Stroke

Screening

Cincinnati Prehospital Stroke Scale

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Los Angeles Prehospital Stroke Screen (LAPSS)

Last time patient known to be symptom free

Screening criteria1. Age >45 y2. No history of seizure or epilepsy3. Symptom duration less than 12 hours4. No previously bedridden or wheelchair bound5. Blood glucose 60-400 mg/Dl

6. Exam: Facial smile/grimace: normal, droop Grip: normal, weak grip, no grip Arm strength: normal, drifts down, falls rapidly

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LOS ANGELES MOTOR SCALE (LAMS)

Normal Right Left Total

Facial smile/grimace

Ͱ (0)Ͱ Droop (1) Ͱ Droop (1)

Grip Ͱ (0)Ͱ Weak grip (1)

Ͱ No grip (2)

Ͱ Weak grip (1)

Ͱ No grip (2)

Arm strengthͰ (0)

Ͱ Drifts down (1)

Ͱ Falls rapidly (2)

Ͱ Drifts down (1)

Ͱ Falls rapidly (2)

TOTAL Score

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Cincinnati Prehospital Stroke Scale

Facial droop Normal : both sides of face more equally Abnormal : one side of face does not move as well as the other

Arm drift Normal : both arms move the same or both arms do not move

at all Abnormal : one arm either does not move or drift down

compared to the other

Speech Normal : says correct words with no slurring Abnormal : slurs words, says the wrong words, or is unable to

speak

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How to approach a patient with probable acute stroke?

New onset of acute neurological deficit

Differential diagnosis of other non-stroke diseases

Subsequent hospital Subsequent hospital managementmanagement

Acute stroke Acute stroke managementmanagement

Establish cause of Establish cause of strokestroke

Stroke risk factorsStroke risk factors Dysphagia screeningDysphagia screening Early rehabilitationEarly rehabilitation

PT, OT, STPT, OT, ST Plan for secondary Plan for secondary

prevention of strokeprevention of stroke

Initial ER assessment and Initial ER assessment and managementmanagement

Vital signs, sugarVital signs, sugar Consciousness: GCSConsciousness: GCS Non-contrast head CTNon-contrast head CT Stroke severity: NIHSSStroke severity: NIHSS Stroke type and locationStroke type and location Hyperacute managementHyperacute management

Thrombolytic therapyThrombolytic therapyCraniectomyCraniectomyIntensive care/monitoringIntensive care/monitoring

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History for initial diagnosis of acute

stroke Rapid, accurate history taking

Often from the family members

Key elements of history Onset time: the last time of normal neurological

status Onset mode: sudden, acute, subacute Onset symptoms: focal or generalized symptoms Course: progression of symptoms Co-morbid diseases: HTN, DM, Heart diseases, etc. Use of medications: antiplatelets, anticoagulants,

antihypertensives, insulin, etc.

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Misdiagnosis of Acute Stroke~ NTUH experience

No. %

Acute stroke 2226 87.6

Misdiagnosis of acute stroke 316 12.4

Possible neurovascular disorders 57 2.2

Other neurological disorders 209 8.2

Non-neurological disorders 50 2.0

Total 2542 100.0

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Differential Diagnosis of Acute Stroke

Old cerebrovascular disease Craniocerebral/cervical trauma Meningitis/encephalitis Hypertensive encephalopathy Intracranial mass (tumor, subdural/epidural hematoma) Seizure with persistent neurological signs (Todd’s paralysis) Vestibulopathy Spinal cord or peripheral nerve lesions Migraine with persistent neurological signs Metabolic:

Hyperglycemia Hypoglycemia post-cardiac arrest hypoxia Infection Drug overdose, etc.

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NTUH ER Stroke Assessment: History

Stroke/TIA Onset Time: 確定 年 月 日 時 分 不確定Stroke/TIA Onset Symptoms:

drowsiness, stupor, delirium, coma,headache, vomiting, neck stiffness,

seizures, anopia, aphasia (sensory, motor), apraxia, vertigo,

dizziness, dysarthria, dysphagia, diplopia, ataxia, incontinence

left side weakness (face, upper limb, lower limb),

right side weakness (face, upper limb, lower limb),

left side numbness (face, upper limb, lower limb),

right side numbness (face, upper limb, lower limb),

Others:

Stroke/TIA Onset Mode: sudden, acute, fluctuating course

Activity at Stroke/TIA Onset: strenuous activity, ordinary activity, rest, sleep

Stroke in Progression: yes (symptoms progression>1 hour), no

Past history: hypertension, DM, AF, others

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NTUH ER Stroke Assessment: NIHSS

1a. Level of Consciousness (LOC) □ 0= Alert □ 1= Not alert, but arousable □ 2= Not alert, obtunded □ 3= Uunresponsive1b. LOC Questions□ 0= Answers both questions

correctly□ 1= Answers one question correctly□ 2= Answers neither question

correctly1c. LOC Commands□ 0= Performs both tasks correctly□ 1= Performs one task correctly□ 2= Performs neither task correctly2. Best Gaze□ 0= Normal□ 1= Partial gaze palsy□ 2= Forced deviation or total gaze

paresis3. Visual□ 0= No visual loss□ 1= Partial hemianopia.□ 2= Complete hemianopia□ 3= Bilateral hemianopia

7. Limb Ataxia□ 0= Absent □ 1= Present in one limb.□ 2= Present in two limbs8. Sensory□ 0= Normal□ 1= Mild to moderate sensory loss□ 2= Severe9. Best Language□ 0= normal□ 1= Mild to moderate aphasia□ 2= Severe aphasia□ 3= Mute, global aphasia10. Dysarthria□ 0= Normal□ 1= Mild to moderate□ 2= Severe11. Extinction and Inattention□ 0= Normal□ 1= One sensory modality□ 2= More than one sensory modality

Total Score:

4. Facial Palsy□ 0= Normal□ 1= Minor □ 2= Partial □ 3= Complete 5a Left Motor Arm□ 0= No drift□ 1= Drift □ 2= Some effort against gravity□ 3= No effort against gravity□ 4= No movement5b. Right Motor Arm□ 0= No drift□ 1= Drift □ 2= Some effort against gravity□ 3= No effort against gravity□ 4= No movement6a. Left Motor Leg□ 0= No drift□ 1= Drift □ 2= Some effort against gravity□ 3= No effort against gravity□ 4= No movement6b. Right Motor Leg□ 0= No drift□ 1= Drift □ 2= Some effort against gravity□ 3= No effort against gravity□ 4= No movement

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NTUH ER Stroke Assessment: Diagnosis

Head CT Findings:

□Hemorrhage

□Ischemia

Early sign:

Diagnosis:

□Ischemic Stroke （□ left, □right ） □ACA; □MCA, total; □MCA, partial; □PCA; □Brainstem, □cerebellum

□Hemorrhagic Stroke (site: )

□Others:

Management Suggestion:

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Head images for acute stroke diagnosis

Everyone with suspected stroke CT without contrast

Some patients required stroke mechanism realization or treatment consideration

MRI MRA CTA Ultrasound (duplex, transcranial Doppler,

Echocardiography) Conventional angiography

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Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal

ganglia (red arrow), and cortical swelling (blue arrows) in the same patient. Right:

Dot sign (yellow arrow) in the left sylvian fissure.

Early CT signs in acute MCA stroke

Alberta Stroke Program Early CT Score (ASPECTS) Quantify the extent of CT hypodensity in acute

stroke

C

A

P

M1

M2

M3

IL

IC

Barber et al. Lancet. 2000;355:1670-4.

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Diagnosis of Acute Stroke

Stroke vs. non-stroke Infarction or hemorrhage Infarction

Location diagnosis Arterial territory diagnosis Pathophysiology diagnosis Etiology diagnosis

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Location Diagnosis of Stroke

Supratentorial site Hemisphere side Cortical or subcortical areas Frontal, parietal, temporal lobe

Infratentorial site Midbrain, pons, medulla, cerebellum

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Arterial Territory Diagnosis of Stroke

ICA: more than MCA territory ACA MCA

Lenticulostriate artery Cortical branches Internal borderzone area

PCA External borderzone area V-B system

Extracranial VA Intracranial

VA, BA, PICA, AICA, SCA

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Acute Stroke Case

A 70-year-old, right-handed man has been

known to have previous history of poorly

controlled hypertension, diabetes, and cardiac

arrhythmia. He developed abrupt onset of left-

sided weakness after dinner at 7 pm.

What should you do?

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Acute Stroke Case

He brought to a medical center ER by the EMS at 8:30 pm. On initial ER arrival, his consciousness was awake, blood pressure was 210/120 mmHg, pulse rate was 120/min irregularly, respiratory rate was 20/min, body temperature was 37°C and blood sugar was 320 mg/dL.

What should you do if you are on duty at ER ?

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Acute Stroke Case

Neurologically, he had flaccid hemiplegia and right-sided gaze preference with dense left-sided hemineglect. The NIHSS score was 17. Head CT scan revealed effacement of cortical sulcal marking in the right middle cerebral artery territory and hyperdense MCA sign.

What is your diagnosis of the stroke ?

What are the next you will do ?

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Diagnosis of Acute Stroke

Stroke confirmed by history and images

Infarction confirmed by head CT

Location right MCA territory (>1/2)

Arterial territory right MCA, main trunk

Pathophysiology embolism

Etiology cardioembolism, atrial

fibrillation

Microembolus

Atheroma

Occlusion Site

Arterial Embolism

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Stroke Evaluation Targets for Potential Thrombolytic Candidates

Time Target

Door to doctor 10 minutes

Door to CT completion 25 minutes

Door to CT read 45 minutes

Door to treatment 60 minutes

Assess to neurological expertise 15 minutes

Assess to neurosurgical expertise 2 hours

Admit to monitored bed 3 hours

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Acute Ischemic Stroke Protocol

ER arrival

Triage nurse confirm stroke onset time < 4 hours

ER Resident performsRapid evaluation (5 minutes)1.exact time of onset2.important history3.quick neurological evaluationSTAT CT and blood work

Neurology Resident receivesER stroke page andproceeds to ERbrief history & physical exam Page Stroke VS

Head CT findings, laboratory data, NIH stroke scaleConfirm the criteria fulfilling thrombolytic therapy for ischemic strokeFamily’s agreement for thrombolytic therapy

Stroke onset < 3 hoursIV-tPA treatment

Patient is admitted to Stroke ICU for intensive monitoring/care

Stroke onset 3-6 hoursIA thrombolytic therapy

Call NeuroradiologistsIA thrombolysis

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Essentials of Acute Stroke Care

Acute stroke team Multi-disciplinary care

Stroke units

Intensive care of stroke patients

Standardized protocol of acute stroke management

Early rehabilitation of acute stroke patients

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Acute Stroke Teams

Acute stroke team consists of health care professional with experience and expertise in stroke

Available 24 hours everyday, within 15 minutes of the call

At a minimum, a qualified acute stroke physician and another health care professional

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Stroke Units

A setting designed for the care of stroke Admission/discharge criteria, patient census

and outcome data Staffed and directed by personnel

(physicians, nurses, etc.) with training and expertise in caring for patients with cerebrovascular disease

Equipment and written protocols for stroke patient care: Neuro, Cardiac, B/P monitoring

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Potential Benefits of Stroke Units

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20

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Gilligan et al. Cerebrovasc Dis. 2005;20:239-44.

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Goal of Acute Ischemic Stroke Care

Treatment goals Therapeutic strategies

To reverse brain ischemia before it cause

permanent brain injury

Recanalization, esp. thrombolysis

To prevent stroke in evolution and recurrence Antithrombotic agents

To optimize the patient’s medical condition and

prevent the common medical sequelae that

occur after stroke or after a stroke intervention

Homeostasis of the brain

To optimize functional recovery after the

residual permanent injury that has occurred

Early rehabilitation

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Homeostasis of the Brain

Blood pressure SBP 120-220 mmHg, DBP 70-

110 mmHg

Blood glucose level blood sugar 100-150 mg/dL

Body temperature <37.5°C

Oxygen saturation >95%

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Blood Pressure in Acute Ischemic Stroke

A spontaneous increase in BP is common in

patients with acute ischemic stroke, and the

increase in BP tends to be more pronounced in

patients with preexisting hypertension.

Elevations in systolic blood pressure >160 mm Hg are detected in 60% of patients with acute stroke.

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Cause of Elevated Blood Pressure in Acute Stroke

Stress of hospitalization Stress of the cerebrovascular event A full bladder, nausea, pain, other body

discomfort Preexisting hypertension A physiological response to hypoxia A response to increased intracranial

pressure

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Blood Pressure in Acute Ischemic Stroke

In a majority of patients, BP tends to decline in the

first few days to weeks after stroke onset, even

without pharmacological intervention.

A significant decline in BP can be seen in

approximately a third of patients in the first few

hours after stroke onset.

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Blood Pressure in Acute Ischemic Stroke

BP often falls spontaneously when the patient is

moved to a quiet room, the patient is allowed to rest,

the bladder is emptied, or the pain is controlled.

In addition, treatment of increased intracranial

pressure may result in a decline in BP.

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Time course of blood pressure (MAP) with acute ischemic stroke

Christensen et al. Acta Neurol Scand 2002;106:142-7.

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Admission Blood Pressure and Outcome ~ International Stroke Trial

Leonardi-Bee et al. Stroke 2002;33:1315-20.

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High Blood Pressure in Acute Stroke and Outcome

For every 10-mm Hg increase >180 mm

Hg, the risk of neurological deterioration

increased by 40% and the risk of poor

outcome increased by 23%

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Cerebral Perfusion Pressure

Cerebral perfusion pressure (CPP) = Mean arterial blood pressure (MABP) – intracranial pressure (ICP)

Maintain CPP >60 mm Hg to ensure cerebral blood flow

In case of elevated ICP, elevated BP is required for maintaining adequate CPP.

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Management of Elevated BP in Acute Ischemic Stroke

Current recommendation based on the type of stroke

Antihypertensive therapy in acute ischemic stroke Aggressive antihypertensive therapy may lower the cerebral

perfusion pressure and lead to stroke worsening Acute stroke patient may have exaggeration of response to

antihypertensive agents For nonthrombolytic candidates

Not to treat if SBP <220, DBP <120, or MAP <130 mm Hg.

For thrombolyic candidates

Not to treat if SBP <185, or DBP <110 mm Hg

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BP Lowering in Acute Ischemic stroke

When treatment is indicated, lowering the BP should be done cautiously.

Some strokes may be secondary to hemodynamic factors, and a declining BP may lead to neurological worsening.

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Blood Pressure Management of Ischemic Stroke (nonthrombolytic candidates)

Blood pressure Treatment

DBP >140 mm Hg Sodium nitroprusside (0.5 ug/kg/min).

Aim for 10-20% reduction in DBP.

SBP >220, DBP >120, or MAP >130 mm Hg

10-20 mg labetalol IV push over 1-2 min.

May repeat or double labetalol every 20 min to a maximum dose of 150 mg.

SBP <220, DBP <120, or MAP <130 mm Hg

Emergent antihypertensive therapy is deferred in the absence of aortic dissection, acute myocardial infarction, severe congestive heart failure, or hypertensive encephalopathy

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Intravenous Medications Considered for Control of Elevated BP in Patients With ICH ~ AHA, 2007

Drug Bolus Dose Continuous Infusion Rate

Labetalol 5~20 mg every 15 min 2 mg/min (maximum 300 mg/d)

Nicardipine NA 5~15 mg/h

Esmolol 250 μg/kg IV push loading dose 25~300 μg/kg/min

Enalapril 1.25~5 mg IV push every 6 h* NA

Hydralazine 5~20 mg IV push every 30 min 1.5~5 μg/kg/min

Nipride NA 0.1~10 μg/kg/min

Nitroglycerin NA 20~400 μg/min

Broderick et al. Stroke. 2007;38.

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Common Intravenous Anti-Hypertensive Drugs Use in ICU

Sodium Nitroprusside (Nipride)

Direct vasodilation

Labetalol (Trandate)

and -1 blockade

Nicardipine (Perdipine)

Calcium channel blockade

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Sodium Nitroprusside

Mechanism : Direct artery and vein dilation

Administration : IV infusion

Onset : Seconds

Duration : Continuous, during infusion

Advantage : Balanced of preload & afterload

Disadvantage : 1. Excessive hypotension

2. Reflex tachycardia

3. Light sensitivity

4. Potential cyanide/thiocyanate toxicity

Dosage : 0.25-10 µg/kg/min IV

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Labetalol

Mechanism : and -1 blockade

Administration : Bolus/infusion

Onset : bolus -- 5~30 min, infusion -- 15~60 min

Duration : 2~12 hrs

Advantage : 1. Little change in HR and CO

2. Intra-A or ICU monitoring (-)

Disadvantage : 1. Orthostatic hypotension

2. Urinary retention

3. -blocker’s contra-indications

Dosage : 10-80 mg IV q10 min up to 300 mg,

IV infusion: 0.5-2 mg/min

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Nicardipine

Mechanism : Calcium blockade, endothelin-1 antagonism

Administration : Bolus/infusion

Onset : 1-5 min

Duration : 3~6 hrs

Advantage : 1. no interference with CBF, CO

2. diuretic effect

3. inhibit platelet aggregation, vasospasm

Disadvantage : 1. hypotension

2. bradycardia

Dosage : 5 mg/h IV, 2.5 mg/h q15 min, up to 15 mg/h

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Blood Glucose within the first 48 hours after stroke

124 patients with ischemic stroke without previously

diagnosed diabetes had blood glucose measured at

least 4-hourly until 48 hours poststroke.

The mean glucose was 6.6 mmol/L throughout the

period of monitoring, with no change over time.

More severe stroke and glucose-lowering therapy to

be associated with higher poststroke glucose levels.

Wong et al. Neurology 2008;70:1036-41.

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Poststroke Hyperglycemia

Persistent hyperglycemia Definition: mean blood glucose >7 mmol/L (126

mg/dL) or HbA1C >6.2%

An independent determinant of infarct expansion

Associated with worse functional outcome

Baird al. Stroke. 2003;34:2208-14.

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Intensive Insulin Therapy in the Medical ICU

A prospective, randomized, controlled study of 1,200

adult patients admitted to the medical ICU.

Comparison between conventional therapy (insulin

administered when blood glucose >215 mg/dL) and

intensive therapy (blood glucose control within 80-110

mg/dL)

Intensive insulin therapy significantly reduced morbidity

among all patients in the medical ICU.

Van den Berghe et al. N Engl J Med. 2006;354:449-61.

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Respiratory Failure in Acute Stroke Patients

Major causes Aspiration pneumonia Impaired central

respiratory drive Neurogenic pulmonary

edema Overall stroke: 10%

Ischemic stroke: 5-6% ICH: 26-30% SAH: 47%

Prognosis: poor in

49-93%

Respiratory function Risk for aspiration,

airway obstruction,

hypoventilation. Target at O2

saturation > 95%

55

Fever and ischemic stroke

Fever correlates with increased severity of stroke, mortality, and poorer prognosis in patients with ischemic stroke

Differentiation of the fever causes central, drug, infection, etc.

Hyperthermia May accelerate cerebral metabolism and neuronal injury A marker of severity of stroke or a consequence of large

strokes is unclear Mild hypothermia

Improve neurological outcome Reduce elevated ICP

56

Causes of Intracranial Hypertension

Intracranial mass

Cerebral edema Cytotoxic (intracellular)

Vasogenic (extracellular)

Cerebrospinal fluid hypervolemia Decreased absorption

Overproduction of CSF

Increased intracranial blood volume Cerebral vasodilatation (hypoxia, hypercapnia)

Obstructed venous outflow

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IICP Management in Acute Ischemic Stroke

Generalcardiopulmonary and

metabolic supportPositioning: elevate head of

the bed to 30o

Treat feverTreat seizureAvoid hypoxia and

hypercapniaAvoid hypo-osmolar fluidsAvoid hyperglycemia

Osmotherapy Mannitol Glycerol Hypertonic saline

Hyperventilation

Surgery Drainage of

cerebrospinal fluid: ventriculostomy, VP shunt

Craniectomy

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Medical Therapy in Acute Ischemic Stroke

Thrombolytic therapy

IV rt-PA therapy

IA rt-PA or urokinase therapy

Combined IV and IA thrombolysis

Antithrombotic therapy

Antiplatelets: aspirin, clopidogrel (Plavix), Aggrenox

Anticoagulants: heparin, low-molecular weight heparin,

warfarin

Neuroprotection: uncertain effect

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Territory infarct vs. borderzone infarct

60         

Penumbrae of Ischemic Stroke

Penumbrae is the target of any reperfusion therapy

The fate of brain tissue depends on Time Cerebral blood flow

Occluded arterial flow Collateral blood flow

Time is brain

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NINDS rt-PA Study Group. NEJM 1995;333:1581-8.

Outcomes in rt-PA-treated Patients Compared with Controls at 3 M After Stroke

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IV Thrombolysis of Acute Ischemic Stroke~ Cochrane Meta-Analysis

death or dependency (mRS 3-6)

treated up to 3 h after stroke

death or dependency (mRS 3-6)

treated up to 6 h after stroke

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Model Etimating OR for Favourable Outcome at 3 M in rt-PA-treated Patients Compared with Controls

Hacke et al. Lancet 2004;363:768-774.

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Cochrane thrombolysis meta-analysissymptomatic (including fatal) intracranial hemorrhage

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 Outcome in SITS-MOST and Pooled Randomised

Controlled Trials at 3 M After Stroke Onset

Wahlgren et al. Lancet 2007;369:275-82.

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ECASS III : IV rt-PA 3~4.5 hoursDistribution of Scores on the Modified Rankin Scale

Hacke et al. N Engl J Med. 2008;359:1317-29.

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ECASS III : IV rt-PA 3~4.5 hours Odds Ratios for Functional End Points at Days 90 and 30 after Treatment

Hacke et al. N Engl J Med. 2008;359:1317-29.

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IV tPA for Acute Ischemic Stroke~ Inclusion Criteria

Ischemic stroke with clearly defined symptom onset

Measurable deficit on the NIH Stroke Scale

Age >18 years

No evidence of intracranial blood on the brain CT scan

Timing from the symptom onset to initiate of IV rt-PA

NINDS (1995) : <3 hours

ECASS-III (2008) : <4.5 hours

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IV tPA for Acute Ischemic Stroke~Exclusion Criteria

Rapidly improving or minor stroke symptoms (NIHSS <4) Severe stroke symptoms by clinical (e.g., NIHSS >25) or head

CT scan (> 1/3 MCA low density) Stroke or serious head trauma within 3 mo Major surgery within 14 d History of intracranial hemorrhage Systolic BP >185 mmHg or diastolic BP >110 mmHg of

treatment initiation Aggressive BP treatment (i.e., continuous IV infusion of

antihypertensive to achieve above goal)

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Suspected SAH despite a normal CT scan Gastrointestinal or urinary tract hemorrhage within 21 d Arterial puncture at a noncompressive site within 7 d Seizure at the onset of stroke with uncertain new stroke Use of heparin within 48 h and an elevated PTT-aPTT Old stroke with diabetes mellitus Use of warfarin and INR >1.7 Platelet count < 100,000/mm3

Glucose < 50 or > 400 mg/dL

IV tPA for Acute Ischemic Stroke~Exclusion Criteria

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Guidelines for IV thrombolysis~ Care during the first 24 hours after administration

of tPA

Admission to a skilled care facility (ICU or acute stroke unit) Careful monitor and management of BP

Keep SBP<185 mmHg, DBP<110 mmHg

No use of anticoagulants and antiplatelet Central venous access and arterial punctures are restricted Placement of an indwelling bladder catheter should be avoided

during drug infusion and for at least 30 minutes after infusion ends

Insertion of a nasogastric tube should be avoided Careful neurological evaluation (NIHSS at 1st, 2nd, 24th hours)

72

Risk of hemorrhagic changes

Marked hyperglycemia

or DM

CT >1/3 MCA

Increasing stroke

severity

Low platelet counts

~ Circulation. 2002

Higher NIHSS score

Longer time to

recanalization

Lower platelet counts

Higher glucose level at

admission

~ Stroke. 2002

73

Guidelines for IV Thrombolysis

~ Bleeding Management

Head CT should be obtained on an emergent basis whenever neurological worsening (NIHSS increase >4)

Any life-threatening hemorrhagic complication, including ICH, should be followed by these sequential steps: Discontinue ongoing infusion of thrombolytic drug Obtain blood samples for coagulation tests

HCT, HB, PT/INR, PTT, PLT, Blood type Obtain surgical consultation, as necessary Consider other interventions that may be useful, such as transfusion

4 units packed RBC, 2 units FFP, 6 units cryoprecipitate, 1 unit PLT

72 female, HT, CAD, AF, Sudden left hemiplegiaInitial NIHSS (1 hour): 19NIHSS 1 week later: 8Hemorrhagic transformation (asymptomatic) of right MCA territory

IV rt-PA in Acute Ischemic StrokeCase Presentation

65 year-old female, no known major systemic diseasesAcute onset, left hemiplegia, neglect, and hemianopia.ER arrival in 1 hour. Initial NIHSS: 15 24 hours after IV-tPA therapy: NIHSS: 3Discharge (10 days later): NIHSS: 0, mRS: 0, Barthel index: 100

IV rt-PA in Acute Ischemic StrokeCase Presentation

76

Intra-arterial Thrombolysis

M2 superior division

M2 inferior division

MCA, M1

ThrombusMicrocatheter

ICA

77

Intra-arterial Thrombolysis

78

Intra-arterial Thrombolysis

Advantage Higher recanalization rate Symptomatic brain hemorrhage

8.3% in the carotid system 6.5% in vertebrobasilar territory No higher than those in IV thrombolysis

Disadvantage Ready availability of neuro-interventionalists, a stroke

team, and a stroke ICU Additional time required to begin treatment compared to

IV thrombolysis

After the microcatheter transverses the thrombus, the first loops of the Merci Retriever are delivered distal to the occlusion site.

The Merci Retriever is pulled back at the contact of the thrombus, additional loops are delivered withinthe thrombus, and the Merci Retriever is torqued to ensnare the thrombus.

The balloon of the balloon guide catheter (BGC) (insert) is inflated to control antegrade flow, and the Merci Retriever is pulled back with the ensnared thrombus toward the tip of the BGC where it is aspirated.

Stroke 2005;36:1432-8.

Mechanical Clot Disruption and Removal– 121 patients with MCA infarct less than 6 h– Some also received IA thrombolysis– Median NIHSS was 19, 40% had baseline NIHSS >20– 114 were treated with MERCI device– Recanalization rate: 54%– Symptomatic brain hemorrhage: 8%

• 5% with retriever alone, 24% with retriever and IA thrombolysis

– Mortality at 3 mo: 40%

80

Alexandrov A et al. N Engl J Med 2004;351:2170-2178

Ultrasound-Enhanced Thrombolysis

Intra-venous rt-PA thrombolysis and continuous 2-MHz

transcranial Doppler ultrasonography <3 hours after stroke onset Augment arterial recanalization Increased neurological recovery

81

Future Treatment of Acute Ischemic Stroke

New thrombolytic agents Combined IV+IA thrombolysis

IV tPA within 3 h, IA tPA 3-6 h Combined thrombolytic agents and antiplatelets Combined thrombolytic agents and anticoagulant Neuroprotection agents MRI diffusion-perfusion mismatch

3-9 h after stroke onset Clot/thrombus retrieval

Ischemic Penumbra

83

Current available antithrombotic agents for acute ischemic stroke

Oral antiplatelet agents Aspirin Ticlopidine Clopidogrel Dipyridamole Aspirin + extended-release

dipyridamole Cilostazol

Glycoprotein IIb/IIIa inhibitors Abciximab Tirofiban Epifibatide

Heparins Unfractionated heparin Low-molecule-weight

heparins Dalteparin Enoxaparin Tinzaparin

Heparinoids Danaparoid

Direct thrombin inhibitors Argatroban Bivalirudin Lepirudin Ximelagatran

84

Antiplatelet in Acute Ischemic Stroke

International Stroke Trial (IST) 19,436 patients, ASA 300 mg/day, <48 hors

Chinese Acute Stroke Trial (CAST) 21,106 patients, ASA 160 mg/day, <48 hours

Combined analysis of ASA vs placebo Absolute risk reduction reduction of deaths or nonfatal

stroke: 0.9% Absolute risk reduction reduction of early stroke

recurrence: 0.7% Small increase in ICH or systemic hemorrhage: IST (1.1%

vs 0.6%), CAST (0.8% vs 0.6%)Stroke 2002;33:1934-42

Effect of various therapies for treatment of acute ischemic stroke

Agent Trial Outcome Effect

Aspirin IST Hemorrhagic stroke at 2 wk Harm of 1 per 1000 (NS)

Death or nonfatal stroke at 2 wk Benefit of 11 per 1000 (p<0.05)

Dead or dependent at 6 mo Benefit of 13 per 1000 (p=0.07)

CAST Hemorrhagic stroke at 2 wk Harm of 2 per 1000 (NS)

Death or nonfatal stroke at 1 mo Benefit of 7 per 1000 (p=0.03)

Dead or dependent at 1 mo Benefit of 11 per 1000 (p=0.08)

Heparin IST Recurrent ischemic stroke at 2 wk Benefit of 9 per 1000 (p<0.01)

(any dose) Hemorrhagic stroke at 2 wk Harm of 8 per 1000 (p<0.0001)

Major extracranial hemorrhage Harm of 9 per 1000 (p<0.0001)

Pulmonary embolism Benefit of 3 per 1000 (p<0.05)

Death or nonfatal stroke at 2 wk Benefit of 4 per 1000 (NS)

Dead or dependent at 6 mo No effect (NS)

Heparin IST Recurrent ischemic stroke at 2 wk Benefit of 12 per 1000 (p<0.001)

5000 U bid Hemorrhagic stroke at 2 wk Harm of 3 per 1000 (p<0.05)

Major extracranial hemorrhage Harm of 2 per 1000 (NS)

Pulmonary embolism Benefit of 12 per 1000 (NS)

Death or nonfatal stroke at 2 wk Benefit of 12 per 1000 (p<0.05)

Dead or dependent at 6 mo Harm of 2 per 1000 (NS)

86

Antithrombotics for Stroke Prevention

Primary stroke prevention Ischemic stroke prevention

Antiplatelets: aspirin, others Cardioembolic stroke prevention

Anticoagulants: warfarin, others

Secondary stroke prevention Ischemic stroke prevention

Antiplatelets: aspirin, dipyridamole, ticlopidine, clopidogrel, glycoprotein IIb/IIIa receptor antagonist

Cardioembolic stroke prevention Anticoagulants: heparin, warfarin, others

87

Decision-making of antithrombotic therapy for acute ischemic stroke

Suspected acute ischemic stroke Head CT No antithrombotic

therapyNot completedor reveals ICH

Eligiblefor t-PA?

YesAdminister t-PA

No

ASA 160-300 mgHead CTat 24 hours

Aspirin intolerance or high risk of recurrent stroke Clopidogrel 75 mg/day

or ASA 25 mg + dipyridamole 200 mg bid

Rapiddiagnosticevaluation

Cardioembolism

Consider anticoagulationWarfarin, INR 2-3 Ifno contraindication,Extreme high riskConsider UFH orLMWH

Large arteryatherothrombosisConsider ASA, clopidogrel, orASA+dipyridamole? anticoagulation

Small arteryocclusion

ASA 100 mg/d

Arterialdissection

Consider ASA,? anticoagulation

Cryptogenic

ASA 100 mg/d