STROKE

Listyo Asist Pujarini, MSc., SpS

Departemen Ilmu Penyakit Saraf
Fakultas Kedokteran UMS
Jumat, 15 Oktober 2010

 Stroke penyebab kematian ke-3 di berbagai

negara
Stroke didpt pd semua gol. umur ttp terutama pd
usia tua dan meningkat dgn tambahnya umur,
Stroke = ggn fungsional otak fokal maupun
global akut, > 24 jam akibat ggn ADO
Dibagi 2 :
1. Perdarahan, insiden 15-30% (intrakranial
dan subarakhnoid)
2. Iskemik, insiden 70-85 %

Definisi Stroke
Stroke adalah gangguan fungsional otak fokal maupun
global yang terjadi secara akut, berasal dari gangguan
aliran darah otak . Termasuk di sini perdarahan
subarachnoid, perdarahan intra-serebral, dan iskemik
atau infark serebri. Tidak termasuk di sini gangguan
peredaran darah otak sepintas, tumor otak, infeksi atau
stroke sekunder karena trauma (WHO, 1986)

Stroke: Definition
Stroke is clinically defined as a
neurologic syndrome characterized
by acute disruption of blood flow to
an area of the brain and
corresponding onset of neurologic
deficits related to the concerned area
of the brain
Nurs Clin N Am 2002;37:35-57

- Contralateral limb weakness

- Contralateral sensory loss
- Disfasia
- Disleksia, disgrafia, diskalkulia
- Disorientasi spasial

- Demensia
- Ggn mood
- Ggn perilaku
- Inkontinensia
- disfungsi olfaktorius
- Disfungsi opticus

Hemianopsia
Homonim
Kontralateral

- Ggn bahasa
- Ggn memori
- Ggn mood
- Ggn perilaku

- Ggn saraf kranial

- Ggn fx vital

Nistagmus
Disartria
Ataksia
Tremor
inkoordinasi

(Wilkinson, 1997)

Komplikasi Stroke

Demensia
Depresi
Kecacatan
Epilepsi
Kontraktur
Peptic ulcer

Bronchopneumonia
Deckubitus
Septikemia
Trombosis vena
profunda
Emboli pulmo
Ggn keseimbangan
cairan

KONDISI
Sangat
emergensi

STROKE ISKEMIK AKUT

STROKE HEMORAGIK

Diastolik > 140 mmHg

Emergensi

Sistolik > 230 mmHg

dan / atau Diastolik 121
140 mmHg

Sistolik > 230 mmHg

dan / atau Diastolik >
140 mmHg

Urgensi

Sistolik 180 230 mmHg

dan / atau Diastolik 105
120 mmHg

Sistolik 180 230

mmHg dan / atau
Distolik 105 140
mmHg

Sistolik < 180 mmHg dan

Diastolik < 105 mmHg

Sistolik < 180 mmHg

dan Diastolik < 105
mmHg

Tunda

GUIDELINE STROKE, 2000

Causes of Stroke

(caspase apoptosis: programmed cell de

(necrosis)

ISCHEMIC CORE AND ISCHEMIC PENUMBRA

(Friedlander 2003)

Ischemic
Injury
Apoptotic
Cell Death
Necrotic
Cell Death

Dr.J.Husada 11-2003

Ischemic Stroke
Incidency : 70-85%
Classification :
1. TIA (transient ischemic attack) : < 24 hours
2. RIND (Reversible Ischemic Neurological
Deficits) normal between 24 48 hours.
Prolonge-RIND normal in max. 3 4 days.
3. Stroke in evolution : worsen stroke ( > 48
hours)
4. Stroke complete : permanent neurologic deficit

2 process in ischemic stroke:

1. Vascular : Aterosclerotic process
2. Biochemistry change /cellular
chemist
Aterosclerotic is a normal response to arterial
endotel injury
Aterosclerotic plaque forming, start in young
Clinical manifestation : acute and tent to occur one
time because sudden plaque rupture

Ischemic Stroke Infarct

When a stroke occurs,
it kills brain cells in
that immediate area
This area of dead cells
is called an infarct
These cells usually die
within minutes to a few
hours after the stroke
starts

Definition of Ischemic Stroke

Almost 80% of strokes
are from an emboli or a
thrombus
Embolic & Thrombotic
strokes are ISCHEMIC
< 15% of strokes are
from hemorrhage, with
an even smaller
percentage caused by
hypoperfusion

Causes of Ischaemic
STROKE
Blockade of blood flow by ateroma, emboli,
and ateroscelerotic

Embolic
Once in your brain, the
embolus eventually
travels to a blood
vessel small enough to
block its passage
The embolus lodges
there, blocking the
blood vessel and
causing a stroke

Thrombotic
A thrombotic
stroke is when a
blood clot forms in
one of the arteries
in the brain, or
supplying the
brain, and grows
and grows until it
is large enough to
block blood flow.

Proses Aterosklerosis

Mediate area are insuficiently supplied with blood, and they die

Dimulai luka sel endotel - permukaan tidak mulus lagi

produksi molekul adesi (ICAM) peningkatan NO terjadi ketidak seimbangan (Depolarisasi) - ggn tonus
vaskuler - aktivasi monosit menjadi makrofag yg
mengambil LDL - foam cell
Foam Cell (sel busa) merupakan komponen penting
pembentuk struktur masa plak

Faktor Risiko Aterosklerosis

Proses aterosklerosis terjadi atau dipercepat dg
adanya faktor risiko yg mempengaruhi sel endotel, shg
terjadi disfungsi endotel
Teori lama :
Hipertensi, DM, perokok, kolesterol, oksidan,
obesitas, olah raga kurang,dll
Teori baru (Braunwald) :
Defisiensi estrogen, homosistein, fibrinogen, faktor
VII, tPA-1, lipoprotein (a), C-reaktif protein, chlamydia
pneumonia, inflamasi, infeksi, genetik (HLA)

Potential Stroke Risk Reduction for Individuals

AHA Guidelines

Factor
Hypertension
Smoking
Diabetes
Hyperlipidemia
Atrial fibrillation
(non-valvular)

Risk reduction with treatment

30% - 40%
50% within 1 year, baseline after 5 years
44% reduction in hypertensive diabetics with tight
blood pressure control
20-30% with statins in patients with known
coronary heart disease
68% (warfarin)
21% (aspirin)

Adapted from Goldstein, et al. Circulation 2001;103:163-182.

Stroke: Classification
Ischemic stroke: Account for 80%. Results from
occlusion in the blood vessel supplying the brain
Thrombotic: Occlusion due to
atherothrombosis of small/large vessels
supplying the brain
Embolic: Occlusion due to embolus arising
either from heart (e.g. atrial fibrillation,
valvular disease) or blood vessel

Classification (contd.)
Hemorrhagic stroke: Account for 20%. Results from
rupture of blood vessels leading to bleeding in brain
Intracerebral: Bleeding within the brain due to
rupture of small blood vessels. Occurs mainly
due to high blood pressure
Subarachnoid: Bleeding around the brain;
commonest cause is rupture of aneurysm. Other
causes: Head injury

Stroke: Predisposing factors

Age (risk doubles for
every decade > age 55)
Gender
(males>females)
Family history of
stroke/TIA
Hypertension
Diabetes
Hyperlipidemia
Hyperhomocysteinemia

Obesity
Smoking
Atrial fibrillation
Sedentary lifestyle
Drug abuse (e.g.
cocaine use)
Hormone replacement
therapy
Oral contraceptive

Risk Factors for Stroke

Non-Modifiable
Risk Factors for Stroke
Age
Sex
Race/ethnicity
Family history

Modifiable Risk Factors for

Stroke6
Hypertension
Diabetes
Smoking
Hyperlipidemia
Carotid stenosis
Atrial fibrillation

Stroke: Symptoms
Onset of stroke symptoms varies as
per type of stroke:
Thrombotic stroke: Develop more
gradually
Embolic stroke: Hits suddenly
Hemorrhagic stroke: Hits suddenly and
continues to worsen

Stroke: Symptoms (contd.)

Dizziness
Confusion
Loss of balance/coordination
Nausea/vomiting
Numbness/weakness on one side of the body
Seizure
Severe headache
Movement disorder/speech disorder/blindness etc
(depending on the area of brain affected)

Transient Ischemic Attack (TIA)

Mini stroke
Stroke symptoms last for less than 24 hours
(usually 10 to 15 mins)
Result as a brief interruption in blood flow to
brain
Every TIA is an emergency
TIA may be a warning sign of a larger stroke
Patients with possible TIA should be evaluated
by a physician

Diagnosis of acute ischemic

stroke
Physical examination: For carotid bruits
Brain imaging (cranial CT and/or MRI): Detect
small vessel disease. Helps to effectively
discriminate between ischemic and hemorrhagic
stroke, and stroke from brain tumours
Doppler ultrasonography/Angiography: Detect
large vessel atherosclerosis
ECG/Echocardiography: Detect cardiac embolism
Exclusion of conditions mimicking stroke
(hypoglycemia, migraine, seizure)

Ischemic stroke diagnostic

algorithm
Excluded hypoglycemia, migraine

Acute focal brain deficit

with aura, post-seizure deficit

< 1 hour

Head CT

TIA (if CT/MR brain imaging

without ischemic lesion)

Ischemic Stroke
Cortical
syndrome
ECG
Echo
CARDIAC
EMBOLISM

Lacunar syndrome

Doppler
MRA
Angiogram

MRI
CT

Vasculopathy
Coagulopathy

LARGE ARTERY
SMALL
OTHER DETERMINED
ATHEROSCLEROSIS VESSEL DISEASE
CAUSE

CRYPTOGENIC
STROKE

Emergency Medical Care for Neurologic

Emergencies
Provide reassurance.
Ensure proper airway and breathing.
Place the patient in a position of comfort.
If you suspect stroke, transport immediately and
notify hospital.
Assess and care for any injuries if you suspect any
type of trauma.

Management of acute ischemic

stroke
Systemic thrombolysis: Intravenous
recombinant tissue plasminogen activator (rtPA): Within 3 hrs of onset of stroke. Dose 0.9
mg/kg, max 90 mg.
Antiplatelet agents: Aspirin 160-300 mg within
24- 48 hrs (not during first 24 hrs following
thrombolytic therapy). Clopidogrel a potential
alternative. Combination of clopidogrel and
aspirin currently being evaluated

Management of acute ischemic

stroke (contd.)
Anticoagulants: Heparin/LMWH are not
recommended in acute treatment of ischemic
stroke. Recommended in setting of atrial
fibrillation, acute MI risk, prosthetic valves,
coagulopathies and for prevention of DVT.
Intra-arterial thrombolytics: An option for
treatment of selected patients with major stroke
of < 6 hrs duration due to large vessel occlusion.

Management of acute ischemic

stroke (contd.)
BP management: Should be kept within higher
normal limits since low BP could precipitate
perfusion failure. Markedly elevated BP
(>220/110mmHg) managed with nitroglycerin,
clonidine, labetalol, sodium nitroprusside. More
aggressive approach is taken if thrombolytic therapy
is instituted
Blood glucose management: Should be kept within
physiological levels using oral or IV glucose (in case
of hypoglycemia)/insulin (in case of hyperglycemia)
Elevated body temperature management:
Antipyretics and use of cooling device can improve
the prognosis

Management of Acute hemorrhagic

stroke
Analgesics/Antianxiety agents: To relieve headache.
Analgesics having sedative properties are beneficial for
patients having sustained trauma (e.g. morphine
sulphate)
Antihypertensives:(e.g. sodium nitroprusside,
labetolol)
Hyperosmotic agents (e.g. mannitol, glycerol,
furosemide): To reduce cerebral edema, and raised
intracranial pressure.
Adequate hydration is necessary
Surgical intervention may occasionally be life saving

Management of TIA
Evaluation within hours after onset of symptoms
CT scan is necessary in all patients
Antiplatelet therapy with aspirin (50-325 mg/d),
consider use of clopidogrel, ticlopidine, or
aspirin-dipyridamole in patients who are
intolerant to aspirin or those who experience
TIA despite aspirin use

Secondary prevention of stroke

Recurrence: Annual risk is 4.5 to 6%. Five year
recurrence rates range from 24 to 42%; one-third
occur within first 30 days, hence high priority
should be given to secondary prevention.
Patients with TIA or stroke have an increased risk
of MI or vascular event.
Management of hypertension (goal <140/85 mm Hg)
Diabetes control (goal<126 mg/dL)

Secondary prevention of stroke

Lipid management: Statins (goal cholesterol<200
mg/dL, LDL<100 mg/dL)
Antiplatelet agents: Aspirin (50-325 mg),
clopidogrel (75 mg). A fixed dose combination of
the two drug may also be used
Anticoagulants: Warfarin (target INR 2 to 3); esp.
recommended in patients with cardioembolic
stroke
Appropriate life style modification (cessation of
smoking, exercise, diet etc)

Surgical interventions
Balloon angioplasty/stenting
Carotid endarterectomy/Bypass
Decompressive surgery

LENTICULOSTRIATE ARTERIES

CONTROL CENTER OF BRAIN

CEREBRI MEDIA ARTERIES

Anterior Cerebral
Artery

Much rarer
The classic
presentation is
proximal arm/
leg weakness
with present of
distal strength,
the so-called
man in a
barrel

Middle Cerebral Artery

Characterized by
weakness of the
contralateral face with
hemianopsia and a
preference of the eyes and
head toward the side of
the involved hemispere
Aphasia in dominant
hemisphere injury
Hemineglect
Involvement restricted to
branches of the MCA may
produces fragment of this
syndrome sparing of leg
strengh

Posterior Cerebral
Artery

Involves the brainstem,

cerebellum, thalamus &
occipital lobes
Present with bilateral limb
weakness or sensory
disturbances, cranial nerve
defisit, ataxia, nausea, and
vomiting or coma
occlusion of the basilar
artery trunk : Present with
hemianopia, memory
disturbance, mild
personality disturbance
Rarely; bilateral
thalamus : a state of
decreased responsiveness
and apathy without motor,
sensory or visual

Memperbaiki perfusi : Trombolitik terapi

Memulihkan aliran darah ke daerah otak Iskemik
Neuroprotektan : Agents iskemik

Melindungi jaringan otak thd kerusakan akibat iskemi

NMDA antagonists : Selfotel, Dextrometorphan
Calcium (Ca++) antagonist (Nimodipine)
NOS inhibitors : Lubeluzole,derivat benzotiazol, 6jam
Anti-oxidants : Tirilazad mesylate, Ebselen
Adhesion molecule antibodies / inhibitor platelet : Aspirin

Edema Serebri
Vasogenic :
kerusakan vaskuler endotel kapiler, gangguan tight
junction, permeabilitas meningkat
Cytotoxic :
gangguan pompa Na, K, ATP ase, Na intrasel
meningkat
Interstisial :
Transudasi

PENATALAKSANAAN HIPERTENSI PADA

STROKE AKUT
STROKE AKUT

Sistolik > 230 mmHg

Diastolik > 140 mmHg

Sistolik > 230 mmHg

Diastolik > 121-140 mmHg

Sistolik 180-230 mmHg

Diastolik 105-120 mmHg
Sistolik < 180 mmHg
Diastolik < 105 mmHg

Ulangi 15'
Sistolik > 230 mmHg
Diastolik 121-140 mmHg

Perdarahan intraserebral
Atau
Ggn end organ
Positif

(Guidelines Stroke,2004)
Obat antihipertensi
parenteral

Negatif

Observasi
Obat antihipertensi oral
Diberikan stl hr ke 7-10

Penurunan Tekanan Darah

Pada stroke iskemik akut,
terdapat salah satu dari:
1. Tekanan sistolik > 220 mmHg
2. Tekanan diastolik > 120 mmHg
3. MAP > 130-140 mmHg
4. Disertai infark miokard akut / gagal jantung atau
ginjal akut / aorta torakalis
Penurunan lebih cepat
Stroke
perdarahan penurunan tekanan darah:
maksimal 20%

Angiotensin Receptor Antagonist

(AIIRA)
Memblok aksi angiotensin II
angiotensinogen
renin

bradikinin

angiotensin I
NON ACE

ACE
Inactive peptide

angiotensin II
Candesartan
AT I -RECEPTOR

DILTIAZEM
Diltiazem adalah penyekat saluran kalsium, obat ini
sebaiknya digunakan melalui infus kontinyu 5-40
mg/kg/mnt daripada suntikan bolus (10 mg
dilarutkan dalam 10 ml salin disuntikan dlm waktu
3-5 mnt).
Penurunan tekanan darah 27,3% dg infus kontinyu
dan 7,5 % dg suntikan bolus. Kecepatan denyut nadi
tdk berubah dg infus kontinyu,sedangkan pada
suntikan bolus kecepatan nadiberkurang sedikit dari
88 sampai 82 per mnt.
Obat ini tdk boleh diberikan pd blok sino-atrial, blok
AV derajat 2 atau 3 dan wanita hamil. Sediaan injeksi
sdh ada di Indonesia.

Citicholine
Mechanism (neuronal)
Increase choline formationnd alter degradation
phosphatydilcholine
Increase glucose uptake, asetilkholine, prevention lipid
radical
Increase glutation
Decrease lipid peroxida
Na/K ATPase modulation

Mechanism (vascular)
Increase CBF
Increase O2 consumtion
Decrease vasculer resistance
(Perdossi, 2004)

Piracetam
Mechanism (neuronal)
Repair cell membran fluidity
Repair neurotransmission
Stimulation adenylate kinase
Mechanism (vascular)
Increase eritrocyte deformability
Decrease platelet hyperagregation
Repir microcirculation
(Perdossi, 2004)

METABOLISME CITICHOLIN & PERANANNYA

DALAM MEMPERBAIKI FUNGSI OTAK
PCCT

Hidrolisa
Citicholine

Choline
Vaskularisasi
Lokal

Asetilasi

Acetylcholin
Betaine

Antioksidan

Otak

Cytidine

Glutation

Cystein

diabsorbsi

Sintesa
Phosphatidilserin
Phosphatidiletanolami
n

Ado
Me
Methionin
Homocystein

Citicholine
1-2 DAG

Phosphatidilkolin
Phospolipid

S-Adenosyl-L-homocystein

1-2 DAG : 1-2 Diasil Gliserol

PCCT : Cytidine triphosphat phosphocholine cytidylyl transferase

M
E
M
B
R
A
N
R
E
P
A
I
R

Mekanisme Kerja Ganda Piracetam

Melindungi Sel

Memperbaiki Fungsi

Jaringan Neuron

Piracetam
Jaringan Serebrovaskuler

Meningkatkan Aliran
Darah Otak

Efek Sitoprotektif Dalam

Pembuluh Darah Otak

Piracetam mengurangi alir masuk Kalsium yang tidak normal ke dalam neuron & sel otot polos pembuluh
darah. Oleh karena itu, Piracetam mempengaruhi sistem saraf dan sistem serebrovaskuler, dimana Piracetam
memiliki efek sitoprotektif dan fungsional

CDP-cholin, pirasetam,
nimodipin, piritinol
CDP-cholin :meningkatkan neurotransmiter
dopaminergik, mengurangi asam radikal bebas,
memperbaiki kerusakan metab lipid mitokondria di
serebral akibat hipoksia
Pirasetam : meningkatkan cholinergik dan
neurotransmiter eksitatori amin (glutamat dan
aspartat) dlm jumlah dan fungsi, mengurangi radikal
bebas, memproteksi metab neuron.

Rehabilitation Program:
Physical therapy :

Mobilization
Walking
Major motor or sensory impairment of the limbs
Prescription of devices, such as a cane or walker

Occupational Therapy :

Fine movements of the hand

Arm function
Utilization of tools
Assistive devices
Ability to function independently

Rehabilitation Program:
Speech Therapy :
Disorders of language
Disorders of articulation
Disorders of swallowing

Objective Stroke Rehabilitation

Stroke rehabilitation is an effort to help stroke patients to
optimize their ability in order to return to their active and
productive way of life.
(Ghresham et al., 1997)
Rehabilitation covers efforts to prevent deterioration and
treatment to stop damage, spasticity and contractus and also
to prevent complication as a result of decubitus
(Gloag, 1985)

Objective :
Rehabilitation is aimed to form new connection pathways
and to reactivate neurons which previously passive. His is
conducted by maximizing neuron capacity of healthy
neurons.
This effort is achieved by exercise which is actually a
relearning process, and at the same time stimulating
functional recovery in the brain and preventing disused
athrophy and other complication as a result of paralysis.

Factors that Influence the

Successfully of Rehabilitation

Cause of stroke
Severity of stroke
Location
Age
Self motivation
Premorbide personality and mood
Family
Social economy
Specific deficit neurology
Onset, duration and intensity
Rehabilitation team

Rehabilitation Started
Stroke rehabilitation more effective when it started in
first day in hospital and the latest of 2-3 days after onset.
(Feigenson)

Stroke patients result emboli/trombosis without

complication need to mobilization within 2-3 days, but
stroke patients result subarahnoid hemorrhage have to
stable previously during 10-14 days before mobilization.
(Swenson)

Stroke patients with intracerebral hemorrhage have to lie

down during 3 weeks. (Toole JF)

Pada kejadian yang jarang intracranial

hemoragik dapat terjadi pada trombosis vena
(Adams, 2002)
Trombosis disebabkan oleh :
- kehamilan
- dehidrasi
- pembedahan
- sepsis
- khemoterapi
- kelainan hiperkoagulasi
Perdarahan terjadi akibat ruptur kapiler,
sekunder akibat stagnasi dari vena( sinus
sagtila superior/vena superfisial)

CURRENTLY AVAILABLE
ANTITHROMBOTIC DRUGS

ANTIPLATELET AGENTS

ANTICOAGULANTS

ORAL

PARENTERAL

ORAL

Aspirin
Dipyridamol
Ticlopidin
Clopidogrel
Cilostazol

GPIIb/IIIa
antagonists

Coumarin
melagatran

PARENTERAL
Heparin
LMWH
Hirudin
Argatroban
Fondaparinux

THROMBOLYTIC
AGENTS

-PARENTERAL
-STREPTOKINASE
-UROKINASE
-tPA

Aspirin
Is the standard against which all other antiplatelet
agents are measured
largely because of its relative safety and extremely low
cost
cyclooxygenase inhibitor irreversible
COX-1 in platelet (TXA2 )
COX-2 in vascular endothelial cells (PGI2 )
long lasting inhibition 7 to 10 days (life span of the
platelet 7 to 10 days)

Action Mechanism of Aspirin

Arachidonic acid
Cyclooxygenase(COX)

Aspirin
COX-1 dependent

Thromboxane
synthetase
Thromboxane A2 (TXA2)
Plt aggregation
Vasoconstriction
Platelet

Endoperoxides
(PGG2, PGH2)

COX-2 dependent

Prostacyclin
synthetase
Prostacyclin (PGI2)
Plt aggregation
Vasodilation
Endothelial cells

Effects of Aspirin
1. Antithrombotic effect
Inhibition of COX by the irreversible acetylation of a
specific serine moiety
Aspirin is 170-fold more potent in inhibiting COX-1
than COX-2
2. Antioxidant effect
Decrease the progression of atherosclerosis
Improves endothelial dysfunction in atherosclerotic
vessel
3. Antiinflammatory effect hs CRP (ASH 2003)

Clopidogrel

Merupakan Platelet adenosine diphosphate (ADP) receptor antagonist.

Mengurangi ikatan ADP shg menghambat agregasi platelet.
Juga menghambat agregasi yg distimulasi trombin, platelet activating factor,
dan kolagen.
Berpengaruh pd platelet setelah ~7-10 hari.

CLOPIDOGREL

C
ADP
ADP

GPllb/llla

Activation

(Fibrinogen receptor)
COX (cyclo-oxygenase)
ADP (adenosine diphosphate)
TXA2 (thromboxane A2)

ASA

COX
TXA 2

1. Jarvis B, Simpson K. Drugs 2000; 60: 34777.

Collagen thrombin
TXA2

Activated
Platelet

Clopidogrel
Ticlopidine
TXA
2

ADP

IV Gp IIb/IIIa
Inhibitors

Gp IIb/IIIa
fibrinogen
receptor

Aspirin

COX
Activation

Adhesive proteins
thrombospondin
fibrinogen
p-selectin
vWF

Coagulation factors
factor V
factor XI
PAI-1

To neighboring
platelet

Degranulation

Thrombin
Serotonin
Epinephrine
Collagen

Inflammatory factors
platelet factor 4
CD 154 (CD 40 ligand)
PDGF

TXA, thromboxane; PDGF, platelet-derived growth factor.

Platelet agonists
ADP
ATP
serotonin
calcium
magnesium