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!