뇌졸뇌졸

학병원 신경과

건

2

n Stroke ( CerebroVascular Disease / Attack, CVD / CVA )

- clinical syndrome of rapid onset focal cerebral deficit, lasting more than 24h with no

apparent cause other than vascular one. (WHO definition)

l Vascular occlusion : Ischemic Stroke (cerebral infarction)

l Vascular rupture : Hemorrhagic Stroke (intracerebral hemorrhage, subarachnoid

hemorrhage)

What is Stroke ?

n Cardiovascular disease- Brain : stroke

- Heart : coronary artery disease (myocardial ischemia : angina, MI)

- Peripheral artery : ASO (AtheroSclerosis Obliterans)

Stroke is a Kind of Cardiovascular Disease

3

연간 사망원

0

200

400

600

800

1000

1200

1400

1600

1800

2000

<10 10대 20대 30대 40대 50대 60대 >70 전체

뇌혈관질환

운수사고

심장질환

간암

간질환

위암

만성폐질환

선천성기형

사고성익수

자살

4

n Ischemic stroke (80 %)

n Lacunar infarction (열공 뇌경색)

n Thrombotic infarction ( 전 뇌경색)

n Embolic infarction (색전 뇌경색)

n Cardiogenic

n Artery - to - artery embolism

n Hemodynamic infarction

( 역학적 뇌경색)

뇌졸 종

n Hemorrhagic Stroke (20%)

n Primary Intracerebral hemorrhage (ICH, 뇌내출 )

n Subarachnoid hemorrhage (SAH, 주 하 뇌출 )

5

n Stroke-like symptoms lasting less than 24 hours

n Reversible cerebral ischemia

n Warning sign for cerebral infarction

n 5 % risk of stroke within next 2 days

n 8 % risk of stroke within 1 month

n 25 % have recurrent event within next 3 months

n 5 % risk of stroke or coronary heart disease per year

n New proposal for TIA

n Infarction with neuroimaging (esp. DWI) despite clinical TIA

n CITS : Cerebral Infarct with Transient Symptoms

TIA (Transient Ischemic Attack, 과 뇌허 )

Ischemic Stroke

7

Atherosclerosis

8

Cerebral IschemiaC

ere

bra

l Blo

od

Flo

w

(cc/

10

0gm

/min

ute

)

10

20

30

50

>50 Normal flow--maintained by autoregulation

30-50 Oligemia--increased O2 extraction

<30 Mild ischemia--increased glycolysis, decreased protein synthesis

<20 Moderate ischemia—the “penumbra,”threshold of electrical failure

<10 Severe ischemia—threshold of ionic failure, membrane depolarization

9

n Small vessel disease (Lacunar infarction)

n Large vessel disease

- Thrombotic

- Artery-to-aretery

- Hemodynamic

n Cardioembolism

n Undetermined

Subtype of ischemic stroke

10

Lacunar infarct (SVO)

LAD -thrombotic

infarctLAD : Artery – to –

artery embolism

LAD -Hemodynamic

infarct

Cardioembolism

Subtype of ischemic stroke

11

n Occlusion of small perforating arteries

n Small Deep Brain Infarction

§ MCA : BG / IC / CR

§ PCA : Thalamus

§ BA : Pons

열공 뇌경색 (Lacunar Infarction)

n Lacunar syndrome

§ Pure Motor Hemiparesis

§ Pure Sensory Stroke

§ Sensorimotor stroke

§ Ataxic hemiparesis

§ Dysarthria – Clumsy hand syndrome

12

n In situ thrombosis

§ Thrombotic occlusion of

large artery

n Artery - to - artery embolism

§ Embolic occlusion from

proximal arterial thrombus

Large Artery Disease

13

n Borderzone Ischemia by Low

Perfusion

n Internal Borderzone

n External Borderzone

n MCA - ACA

n MCA - PCA

Hemodynamic Infarction

14

n Arrhythmia

- Atrial Fibrillation / Sick Sinus Syndrome

n Valvular Heart Disease

- Mitral Stenosis / Prosthetic Valve

n Ischemic Heart Disease

- Acute MI / LV Aneurysm

n Others

- Dilated cardiomyopathy

- PFO ( R -> L shunt)

Cardioembolism

15

• Past and Present Medical Illness and Risk Factors

• Hypertension, Diabetes

• Coronary artery disease

• Claudication

• Smoking, Illicit drugs

• Family history of vascular disease

• Past Strokes and TIAs (specific queries)

• Activity at onset

• Associated Symptoms (headache, vomiting, consciousness)

• Temporal course

– Maximal at onset

– Gradual progressive

– Stepwise, fluctuating, stuttering

뇌졸 단 (1)

• 찰 : 병 청취 ( 험 ), 학적 / 신경학적 찰

16

n 뇌 상 촬 (Brain Imaging)

n 뇌전산 단 촬 (Brain CT)

n 뇌 공 상 촬 (Brain MRI)

n 뇌 촬

n 뇌 공 촬 (Brain MRA)

n 전산 단 촬 (CT Angiography)

n 뇌 조 술 (Cerebral Angiography)

n 경동맥 플러 (Carotid Duplex)

뇌졸 단 (2)

n 뇌 검사

n 경 개 플러 초 파 검사

(Transcranial Doppler Ultrasonography)

n 핵 학 검사 - Brain SPECT

n 뇌 공 (Brain Perfusion MRI)

n 타 검사

n Cardioembolism W/U

n 심 초 파 검사 (TTE, TEE)

n 24시간 심전 (Halter monitoring)

n 험 조사

17

Brain CT

18

n Routine Brain MRI

- T1WI, T2WI, FLAIR

n Gradient Echo Image (GRE)

- Hemorrhage

n Diffusion Weighted Image (DWI)

n Perfusion Weighted Image (PWI)

Brain MRI

19

Brain CT Brain MRI

20

Brain MRI : DWI

17 days10 hours

21

Brain MRI : DWI

22

CT angiography & MRA

23

TFCA

24

Brain SPECT

Current Therapy in Acute Ischemic Stroke

26

Treatment of Acute Ischemic Stroke

n How long is “acute” period ? < 24 hours24 hours ~ 5 days

n Save Penumbral zone : ~ hours (narrow time window)

n Thrombolytic therapy (IV or IA)

n General Conservative Management

n To reduce neuronal damage

n Oxygenation / Fluid / Blood Pressure / Glucose / Temperature

n Prevent Progression / Early Recurrence : ~ days

n Antithrombotic therapy : anticoagulants / antiplatelets

n Others : Neuropotection / surgical decompression / hypothermia

27

n 경동맥 전 해술 (Intra-arterial thrombolysis)

n 경정맥 전 해술 (Intravenous thrombolysis)

n IV rt-PA thrombolysis (NINDS study)

n 제한

n Strict inclusion criteria (time < 3 h of onset)

n

n Symptomatic hemorrhage (6.7 %)

Thrombolytic Therapy

28

Ischemic Core

Penumbra

29

Ischemic Core/ Penumbra -> Diffusion / Perfusion Mismatch

30

31

32

• NINDS tPA trial: benefit / 0-3 hours

• ECASS I : failed / 0-6 hours

• ECASS II: failed / 0-6 hours

• ATANTIS: failed / 3-5 hours

• STAT: benefit / 0-3 hours

IV Thrombolysis Trial

33

34

35

Graph of model estimating OR for favorable outcome at 3 months in rt-PA treated patients compared to placebo treated patients by time from stroke onset to treatment

“Time is brain!”

36

prospective, randomized, placebo-controlled phase II study evaluated the utility of intra-arterial administration of recombinant prourokinase (PROACT II)

• < 6 hours’ duration secondary to occlusion of the MCA

• Recanalization of the MCA was achieved in 66% of the patients treated with r-proUK and 18% of the patients in the control group

(P < 0.001)

• no difference in overall mortality

Intra-Arterial Thrombolysis

37

Combining intravenous and intra-arterial rtPA

early intravenous administration of rtPA in a lower dose followed by arterial administration

Recommendations

IA thrombolysis is an option for treatment of selected patients with major stroke of < 6 hours’ duration due to large vessel occlusions of the MCA

38

경동맥 전 해 료 - I

경동맥 전 해 료 - II

40

• Progressing non-hemorrhagic stroke• Cardioembolism (intracardiac thrombus or AF with CHF)• History of frequent or crescendo TIAs• High-grade symptomatic stenosis• Cerebral venous thrombosis • Arterial dissection

• risk of early recurrent embolism : low rates (0.3% to 0.5%/d)

• Although heparin was effective in lowering the risk of early recurrent stroke, including among patients with AF, an increasedrate of bleeding complications negated this benefit

Anticoagulants

41

• Low-Molecular-Weight Heparins• Heparinoid

Recommendations• Urgent routine anticoagulation with the goal of improving

neurological outcomes or preventing early recurrent stroke is not recommended

• More studies are required to determine if certain subgroups (large-vessel atherothrombosis or high risk of recurrent embolism) may benefit

Anticoagulants

42

• Aspirin

Aspirin should be given within 24 to 48 hours of stroke onset in most patients

• Other Antiplatelet Agents

Potent inhibitors of the glycoprotein IIb/IIIa receptor ; Abciximab

Cilostazol (Plataal®)

Triflusal (Disgren®)

Ticlopidine (Clid®)

Clopidogrel (Plavix®)

Aspirin + Dipyridamole (Aggrenox®)

Antiplatelet Agents

43

• Subdural/epidural haematoma or SAH

• Spontaneous ICH

• Necessity for monitoring of ICP

• Cerebellar infarction or haemorrhage with potential threat of brain stem compression

• Imminent brain herniation due to malignant (oedematous) infarction

Surgical Interventions

44

F/79, 식저하, 좌 편 비

- 첫 CT(발병 6 시간) 및 추적 CT (발병 48 시간) CT

45Onset2 daysHemicraniectomy3 Months later

46

47

• Carotid Endarterectomy(CEA)

• EC-IC Bypass

• Because of the lack of evidence about the safety and efficacy of emergent CEA or other surgical procedures, these procedures are not recommended for treatment of most patients with acute ischemic stroke outside of a research setting

Surgical Vascular Interventions

48

Carotid Endarterectomy (CEA)

Symptomatic > 70% stenosis (perioperative morbidity / mortality < 5%)

Asymptomatic > 60% stenosis (perioperative morbidity / mortality < 3 %)

49

• Direct mechanical balloon angioplasty of the thrombus

• Mechanical removal of clot from the middle cerebral artery

• Intravascular stenting

• Suction thrombectomy

• Laser-assisted thrombolysis of emboli

• Power-assisted Doppler thrombolysis

No controlled data on the safety and efficacy of these interventions are available

Endovascular Treatment

50

51

Embolectomy in Acute Stroke: MERCI (mechanical embolus removal in cerebral ischemia trial)

52

• Nimodipine, Flunarizine, NMDA receptor antagonists, Lubeluzole, Glutamate antagonist(selfotel), GABA agonist(clomethiazole), Neurotrophic factors, Glycine site antagonists(gavestinel), Gangliosides, Murine monoclonal antibody to human ICAM-1(enlimomab)

• Citicoline, Magnesium

• No agent with putative neuroprotective effects can be recommended for the treatment of patients with acute ischemic stroke at this time

Neuroprotective Agents

53

• Airway, Ventilatory Support, and Supplemental Oxygen

• Fever

associated with poor neurological outcome, possibly due to increased metabolic demands, enhanced release of neurotransmitters, and increased free radical production

• Cardiac Rhythm

MI and cardiac arrhythmias are potential complications of acute ischemic stroke

• ICP control, if needed

General Supportive Managements

54

• Volume Expansion, Vasodilators, and Induced Hypertension

- Drug-induced hypertension and isovolemic or hypervolemichemodilution

- the risk of myocardial ischemia, CHF, pulmonary edema, ICH, hypertensive encephalopathy, or increased brain edema

-> close observation and cardiovascular monitoring

• Two trials of hemodilution therapy for treatment of patients with acute stroke showed no improvement in outcomes

-> not recommended outside a clinical trial setting for the treatment of most patients with acute ischemic stroke

General Supportive Managements

55

• Hyperglycemia

Increasing tissue acidosis secondary to anaerobic glycolysis and increased blood-brain barrier permeability

• Arterial Hypertension

The consensus is that antihypertensive agents should be withheld unless the diastolic BP is > 120 mm Hg or unless the systolic BP > is 220 mm Hg

* Sublingual use of a calcium antagonist, such as nifedipine, should be avoided because of rapid absorption and a secondary precipitous decline in BP

General Supportive Managements

56

57

Recovery After Stroke

n Over 6 ~ 12 Months

n Early rehabilitation is beneficial

n Mechanisms

n Recruitment

n Functional Reorganization : Neural Plasticity

58

Specific Therapy

Anti - thrombotic drugs

Other drugs

Carotid Endarterectomy / Angioplasty

Prevention of Ischemic Stroke

Risk Factor Control

Non – correctable

Correctable

New Risk Factors

59

60

55 10 가 다

뇌졸 발생 약 2배씩 가

나이

여 보다 남 에게 뇌졸

발생 25-30% 높다.

성별

61

뇌졸 앓았 , 뇌졸

발생 2.4배, 뇌졸

앓았 1.4배 가.

가족력

비흡연 1.5배 흡연량 많 수

뇌졸 발생 가한다. 1년간 연하

뇌졸 발생 흡연 50% 감 하고,

5년 상 연하 비흡연 수 감 .

흡연

62

당뇨병 에 뇌졸발생 정상 약 2배.

당뇨병심장병

심근경색, 심 , 좌심실비 , 심 전

및 심 판 등 경 뇌졸

발생 2 ~ 4 배 가.

심방 동 경 5 ~ 17배 가

63

Hypertension

In general, for a 10 mmHg rise in

approximate mean usual blood pressure

about 30% increase in stroke risk occur.

Goal:

<140/90 mmHg;

<130/85 mmHg if renal insufficiency or

heart failure is present

<130/80 mmHg if diabetes is present.

• ACEI and AT1 receptor blockade:

- Stroke prevention beyond BP lowering alone

- Stabilizing effects on atherosclerotic plaque

by reducing oxidative stress and inflammatory

and proliferative responses

64

Hyperlipidemia- No clear association between elevated cholesterol levels and total stroke : debate

- Low cholesterol may be associated with hemorrhagic stroke

- LDL cholesterol: primary target & strongest correlation with coronary heart disease

- Statins : reduce the risk of stroke in clinical trials of patients with coronary heart disease

Risk category LDL Goal(mg/dl)

CHD and CHD risk equivalents < 100

multiple(2+) risk factor < 130

0-1 risk factor < 160

Statin- HMG-CoA reductase inhibitor

- Stroke preventive effect beyond cholesterol lowering

: Plaque stabilization

: Anti – thrombotic

: Anti - inflammatory

65

Alcohol Consumption

• Relationship between alcohol consumption vs stroke risk : “JJ” shape

• Moderate consumption appears to protect against stroke:

Drinking in moderation is beneficial for those who drink alcohol, no health

contraindication to alcohol use

(National Stroke Association Stroke Prevention Guidelines)

• Limit alcohol intake (2 drinks/d in men, 1 drink/d in women) among those who drink.

• People who do not drink should not be encouraged to do so

66

67

68

69

New Risk Factors

• Only 50 ~ 60 % of atherosclerotic vascular disease can be explained by conventional risk factors

• New risk factors

– Inflammation : CRP

– Infection : Chlamydia pneumoniae, periodontal disease

– Sleep disordered breathing

– Homocyst(e)ine

70

PRIMARY PREVENTION

SECONDARY PREVENTION

ORGANISATION OF STROKE SERVICES

SECONDARY PREVENTION

PRIMARY PREVENTION

ACUTE CARE

COMPREHENSIVE REHABILITATION

Spontaneous IntracerebralHemorrhage

: Causes and Management

72

Cerebral Hemorrhage

• 10-20% stroke

• 20-30% in Asia

• Up to 50%, 30 day mortality

• Little effective therapy

• New therapies will be based on pathophysiology

73

ICH – Worse Outcomes than Ischemic Stroke

American Heart Association. Heart Disease and Stroke Statistics-2005 UpdateQureshi AI. et al. N Engl J Med. 2001;344:1450-1460Broderick JP. et al. Stroke. 1999;30:905-915Broderick JP. et al. N Engl J Med. 1992;326:733-736

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ICH Ischemic

Dead

Dependent

Independent

74

Contents

• Overview of Pathophysiologic mechanism- Hematoma formation and volume, hematoma growth - Perilesional hypoperfusion, ischemia?- Perilesional edema

• Medical therapy- Blood pressure management- Intracranial pressure management- Seizure management and prophylaxis- Hemostatic therapy (rFVII)

• Surgical management (STICH trial)

75

Adverse Prognostic Factors

• Age

• ICH volume

• ICH growth

• Low GCS

• Intraventricular blood

• Infratentorial site

76

Prognosis: ICH score

GCSGCS

ICH volumeICH volume(cm(cm33))

IVHIVH

InfratentorialInfratentorial

Age >80 yrAge >80 yr

33--4455--1212

1313--1515³³ 3030< 30< 30YesYesNoNoYesYesNoNoYesYesNoNo

2211001100110011001100

ItemsItems PointsPoints Total scoresTotal scores 3030--d mortalityd mortality

001122334455

0%0%13%13%26%26%72%72%97%97%

100%100%

Stroke 2001;32:891Stroke 2001;32:891--897897

77

Hematoma Volume

• Expect good recovery for small volume <10 mL*

– e.g. (2x3x3)

• Mortality 90% for comatose patients with large volume >60 mL*

– e.g. (4x5x6)

Volume = (x)(y)(z) / 2

78

28 mL

43 mL

Image courtesy T. Brott, MD.

79

Pathophysiological Changes

• Hematoma formation

• Hematoma growth

• Peri-ICH ischemia ?

• Breakdown of blood brain barrier, perilesional edema

• Neuronal, glial cell death – necrosis, apoptosis, inflammation

80

Pathophysiological Changes:Hematoma growth

• Hematomas expand on serial CT studies

– 38% <24 hours (26% < 1 hour after initial CT ; 12% 1-20 hours)Brott et al., Stroke 1997

– 20% (41 of 204)36% < 3 hour vs. 11 % > 3hours Kazui et al., Stroke 1996

2 hour2 hour 6.5 hour6.5 hour

81

Pathophysiological Changes:Hematoma growth

• Continued bleeding or rebleeding

• Adverse prognosis

• Is associated with acute hypertension, local coagulation deficits, or both. Broderick et al. J Neurosurg 1990

Kazui et al. Stroke1997

• Potential for therapy if bleeding attenuated

82

Pathophysiological Changes:peri-hematomal edema & ischemia

• Etiology and significance remain unknown

• Microvascular compression & ischemia -> cytotoxic edema?

- Oligemia is self limited, spontaneously nomalizing by 3 to 5

days after onset

- Perihematomal edema is plasma derived

: oncotic forces of excess serum proteins associated with

hemostasis

- PET study : perihematomal hypoprefusion was not

exacerbated by BP reduction

83

Blood Pressure Management

• BP Reduction

– Potential benefits:

• May ameliorate local edema

• May limit early hematoma growth

– Potential risk:

• Aggravation of perilesional ischemia?

• No RCT on optimal therapy of acute BP elevation following ICH.

• OPTION: Maintain MAP <130 mm Hg (AHA guideline)• Aggressive option: MAP ≤105 mm Hg

Broderick et al. Stroke. 1999;30:905

84

Blood Pressure Management

• BP Reduction: preferred IV agents

– Labetolol or esmolol (b blockers)

– Nicardipine (CCB)

• Best to avoid

– Nitroprusside

• Can simultaneously increase ICP lower MAP, and severely decreaseCPP

Rose J. and Mayer SA. Neurocritical Care. 2004;1:287

85

Intracranial Pressure Management

• Related to mass effect and perihematomal edema

• To lower ICP <20mmHg and maintain CPP > 70 mmHg

• Monitoring ICP

• Hyperventilation and osmotherapy (mannitol): longterm outcome after reversal of transtentorial herniation

Qureshi AI. Crit Care Med 2000

• Steroids ???

• Neuromuscular blocker with adequate sedation

• High dose barbiturate, hypertonic saline?

• Emergent ICP control- 1.0 – 1.5g/kg of mannitol- artificial hyperventilation to pCO2 28-32mg

86

Cerebral Edema

• Osmolar therapy

– Glycerol has no effect on outcome

– High-dose 20% mannitol (1.4 g/kg) results in better ICP control and outcome than lower doses

– GUIDELINE: Mannitol 20% for patients with increased ICP or symptomatic mass effect

– OPTION: 23.4% Hypertonic saline Yu YL. et al. Stroke. 1992; 23:967Cruz J. et al. Neurosurgery. 2002; 51:628

87

Cerebral Edema

• Dexamethasone

– No benefit on outcome, but complications (infections and hyperglycemia) are more common

– STANDARD: No Steroids!Poungvarin N. et al. N Engl J Med. 1987;316:1229Tellz H. et al. Stroke. 1973;4(4):541-6

88

Cochrane Review: Steroid in ICH

89

ICH: Seizure Prophylaxis

• Seizure after ICH

– 10% have generalized tonic-clonic seizures

– OPTION: Prophylactic phenytoin for 7 days for patients with large (especially lobar) ICH at risk for increased ICP

Passero S. et al. Epilepsia. 2002;43:1175

90

3 hours3 hours

9 hours9 hours

Hemostatic Therapy for ICH

91

Hemostatic Therapy for ICH

N Eng J Med 2005;352:777N Eng J Med 2005;352:777--785785

92

n = 108

16%

Estimated Mean Percent Change in ICH at 24 Hours

Percent change in ICH volume: Baseline ® 24 hours

n = 96

n = 92

n = 103

29%

14%

11%

p=0.015*

p=0.012*

160 µg/kg80 µg/kg40 µg/kgPlacebo

n = 303

CombinedTreatment \

14%

*ICTR values

0

5

10

15

20

25

30

35

% I

ncre

ase

93

Goals of Surgery for ICH

• Prevent herniation

• Prevent death

• Improve functional outcome

• Are these all the same?

94

Surgical therapy

95

Surgical Issues

• Evidence that it works?

• Timing: Ultra-early, early, late?

• Preventing rebleeding?

• Blood pressure management?

• Technique: Craniotomy, stereotactic, endoscopic?

• Adjunctive neuroprotection?

96

Lancet 2005; 365: 387–97

97

Primary Outcome: Death or Disability at 6 Months

–1Not recorded

–378 (76%)346 (74%)Unfavourable

2.3 (-3.2-7.7)118 (24%)122 (26%)Favourable

Absolute benefit

(95% CI)

Initial conservative

treatment (n=497)

Early surgery (n=468)

98

Secondary Outcome at 6 Months

–189 (37%)173 (36%)Dead

1.2 (-4.9-7.2)316 (63%)304 (64%)Alive

Mortality

Absolute benefit

(95% CI)

Initial conservative

treatment (n=497)

Early surgery (n=468)

99

STICH (3)

• Only sub-group to show benefit: if the haematoma was 1 cm or less from the cortical surface (absolute benefit 8%; 0-15%)

100

Issues with STICH

• “Policy” to randomize

• Cross-overs

• Time to surgery

• Multiple surgery strategies

• Lack of defined best medical treatment

101

Acute Stroke is an Emergency

All patients with acute stroke should be cared in

Stroke Unit by Stroke Team with standard protocols

- Neurologist

- Neurosurgeon

- Neuroloradiologist

- Stroke Nurse

My Hope is …….

102

Thank you foryour attention!