• Aterotrombotik • Arteri cerebral anterior

• Perdarahan • Arteri cerebral media

• Common cause of ischemic stroke • Arteri cerebral posterior
• Ischemic Cascade • TCD
• Circulus Willisi • INR
• Klasifikasi stroke iskemik • Anatomi brain
• Nervus VII • Modified Ranking Scale
• Homonculus motorik • NIHSS
• Corticospinal Pathway • AHA / ASA Guideline
• Stroke glukosa dan oksigen • Diagnositic test ASA Guideline
• Stroke insidensi • Oedema cerebri
• Stroke Faktor resiko
aterotrombotik
• ASGM
• Etiologi stroke
• Progresivitas aterotrombotik
• Infark vs Hemoragik
• Stroke physiological changes
Back
Back
 The common causes of ischaemic stroke:

Embolism of thrombus via or from the heart (30%)

• Emboli of cardiac origin are common and those patients who
suffer from Atrial Fibrillation, Infective Endocarditis, or have
recently suffered a Myocardial Infarction are at a higher risk
of developing thrombus within the heart and therefore have a
higher risk of embolus. The embolised material may range
from a thrombus (developed in areas of flow turbulence or at
atherosclerotic points), fat (from bone marrow in a broken
bone), air, cancer cells, or bacteria (usually from Infective
Endocarditis).
 The common causes of ischaemic stroke:

Large Artery Atherothrombosis or

thromboembolism (40-45%)
• This is also called ‘large vessel stroke’.
Atherosclerosis of the larger arteries leads to
stenosis (narrowing) and possibly even full Occlusio
of the vessels causes a decrease in blood flow and
therefore blood supply to the brain tissues.
Atherosclerosis is much more common at the
bifurcations of arteries in the Circle of Willis or the
vertebral artery. It is also common in the carotid
arteries (carotid stenosis
 The common causes of ischaemic stroke:

Small artery microatheroma/ lipohyalinosis

(25%)
This is also called ‘small vessel stroke’. Small lacunar
infarcts of the deeper brain tissue occur due to occlusion
(through the process of atherosclerosis) or rupture of the
small penetrating cerebral vessels (the ‘end arteries’). The
Lenticulostriate perforators are those smaller vessels
commonly affected, which arise at the commencement of
the middle cerebral artery. If they are damaged in anyway,
it is the deep structures of the brain that they supply which
are damaged and small cavity type lesions (~5mm) are
very common.
 The common causes of ischaemic stroke:

Haematological disorders causing a

prothrombotic state (< 5%)

• For example, sickle cell anaemia can cause blood to

clump up and block vessels. Stroke is the second
leading killer of people under the age of 20 who suffer
from sickle-cell anaemia.

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Back
Back
Ischaemic Strokes are also classified according to the
vessels involved:

• TACI – Total Anterior Cerebral Infarction        17%

• PACI – Posterior Anterior Cerebral Infarction 34%
• POCI – Posterior Cerebral Infarction             24%
• LACI – Lacunar Cerebral Infarction                25%

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Back
Back
 Stroke glukosa & oksigen
• Otak memerlukan 6 ml/100gr jar. otak/menit oksigen untuk subs
grisea
• 2 ml/100gr jaringan otak/menit untuk substansia alba
• Kebutuhan glukosa 4.5 - 7 mg/100 gr jaringan otak/menit.
• Terbentuk fosfat berenergi tinggi yaitu ATP dan ADP, melalui citric
acid cycle dan rantai transport elektron mitokhondria
• Dalam keadaan normal tidak terjadi penguraian glukosa secara
anaerobik
• Otak menuntut sekitar 20% dari seluruh output jantung, yaitu
sekitar 800 ml/menit

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 CBF Disturbances

• Normal : CBF 50 – 60ml/100 gr per mnts

• Ischemia : CBF < 30 ml/ 100 gr per mnts
• Penumbra : CBF 15 – 30 ml/100 gr per mnts
• Neuron death :CBF < 10 ml/100 gr per mnts

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 Ischemic

< 20 : aktifitas listrik hilang

< 10 : Gangguan homeostasis
Konsep penumbra
 Stroke insidensi

Ischemic Hemorrhagic
80% 20%
 Stroke insidensi

• Infark : Insidensi 80% - mortalitas 40%

– 50% Thrombotic – atherosclerosis
• Large-vessel 30% (carotid, middle cerebral)
• Small vessel 20% (lacunar stroke)
– 30% Embolic (heart dis / atherosclerosis)
• Young, rapid, extensive.
• Hemorrhage: Insidensi 20% - mortalitas 80%
– Intracerebral atau subarachnoid.
– aneurysm, hypertension/congenital.
Back
 Modifiable
Stroke Faktor resiko  Arterial hypertension
 Hypercholesterolemia
 Cigarette smoking
 Diabetes Mellitus
 Hyperhomocysteinemia
Non modifiable
 Alcohol abuse
 Age
 Oral contraceptive
 Gender
 Menopause
 Ras
 Physical inactivity
 Herediter
 Obesity
 Atrial Fibrillation
 Hipercoagulability
 Multiple faktor risiko Aterotrombosis

Generalized Lifestyle
Disorders • Smoking
• Age • Diet
• Obesity • Lack of exercise

Systemic
Conditions
Atherothrombotic • Hypertension
Genetic Traits • Hyperlipidemia
• Gender Manifestations
• Diabetes
• PlA2 (MI, stroke, • Hypercoagulable
vascular death) states
• Homocysteinemia

Inflammation
Local Factors
• Elevated CRP
• Blood flow patterns
• CD40 Ligand, IL-6
• Shear stress
• Prothrombotic factors (F I and II) • Vessel diameter
• Fibrinogen • Arterial wall structure
• % arterial stenosis
MI, myocardial infarction.
Adapted from Yusuf S, et al. Circulation. 2001;104:2746-2753. Back
Drouet L. Cerebrovasc Dis. 2002;13(suppl 1):1-6.
 ALGORITMA STROKE GADJAH MADA

penderita stroke akut

dengan atau tanpa

penurunan kes., nyeri kepala, refleks babinski

3 atau 2 dari 1 dari ketiganya tidak ada

ketiganya ada ada ketiganya

stroke perdarahan stroke iskemik akut

(stroke infark)

penurunan kes. ada, nyeri kepala

dan refleks babinski tidak ada
atau
nyeri kepala ada, penurunan kes.,
dan refleks babinski tidak ada
refleks babinski ada,
penurunan kes. dan
nyeri kepala tidak ada
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 Characteristics of stroke

Feature Hemorrhage Infarct

Onset sedentary With activity Nocturnal

Hypertension present Usually present Often

Clinical course static Rapidly progressive Stepwise or static

Signs of ICP Present Absent later

CT scan changes Presence of blood Normal or subtle

changes

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 Etiology Stroke :
• Atherosclerosis
– Risk Factors: Hypertension, Diabetes,
Smoking.
• Vasculitis – Infective, Autoimmune.
• Embolism:
– Major artery Atherosclerosis.
– Heart Disease – MI, Valve disease & Atrial
fibrillation.
– Tumor embolism, septicemia, Fat etc.
 Cerebral Embolism Formation

A small clot may break off from a larger thrombus and be carried to other
places in the bloodstream.  When the embolus reaches an artery too
narrow to pass through and becomes lodged, blood flow distal to the
fragment ceases, resulting in infarction of distal brain tissue due to lack of
nutrients and oxygen.
As a cause of stroke, embolism accounts for approximately 32% of cases.
 Stroke Non Hemoragik - Etiologi

1. Thrombosis Cerebral.
Pembuluh darah yang mengalami oklusi  iskemi jaringan
otak  oedema dan kongesti di sekitarnya.

a. Atherosklerosis

b. Hypercoagulasi pada polysitemia

Darah bertambah kental , peningkatan viskositas /hematokrit
meningkat dapat melambatkan aliran darah serebral.

c. Arteritis( radang pada arteri )

Back
 Progresivitas Aterotrombosis

Trombosis

Unstable
angina ACS
MI
Ischemic
stroke
Critical leg
ischemia
Aterosklerosis Intermitent
claudication
CV death

Stable angina/
Intermittent claudication
 Atherosclerotic Plaque

Stable Unstable

Lumen

Endothelium
Thrombus
Platelets

Lipid Rich Core

Thick Thin
Fibrous Cap Fibrous Cap

Falk E et al. Circulation. 1995;92:657–671.

Plak Aterosklerotik
1. Akumulasi lipoprotein pd tunika intima 2. Stres oksidatif
3. Aktivasi Citokine 4. Penetrasi Monocyte
5. Migrasi makrofag  foam cell 6. Muscle Cell Smooth
7. Akumulasi matriks ekstraseluler 8. Kalsifikasi dan fibrosis
 Faktor Risiko Ruptur Plak
Faktor Lokal Faktor Sistemik
Kelelahan Smoking

Cholesterol
Atheromatous Core
(size/consistency)
Diabetes
Mellitus Fibrinogen
Ketebalan /
konsistensi
Homocysteine
Inflamasi Impaired
Fibrinolysis

Plaque
Rupture
Fuster V, et al. N Engl J Med. 1992;326:310-318.
Falk E, et al. Circulation. 1995:92:657-671.

Back
2. Emboli
Emboli serebral merupakan penyumbatan pembuluh
darah otak oleh bekuan darah, lemak dan udara.
Keadaan yang dapat menimbulkan emboli :
a. Katup-katup jantung yang rusak akibat Rheumatik
Heart Desease.(RHD)
b. Myokard infark
c. Fibrilasi.
Keadaan aritmia menyebabkan berbagai bentuk
pengosongan ventrikel sehingga darah terbentuk
gumpalan kecil dan sewaktu-waktu kosong sama sekali
dengan mengeluarkan embolus-embolus kecil.
d. Endokarditis oleh bakteri dan non bakteri,
 terbentuknya gumpalan pada endocardium.
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 Stroke infark

Ischemic
Injury
Apoptotic
Cell Death
Necrotic
Cell Death

-
Stroke infark
Stroke infark
Stroke
 Cerebral Embolism Formation

A small clot may break off from a larger thrombus and be carried to other
places in the bloodstream.  When the embolus reaches an artery too
narrow to pass through and becomes lodged, blood flow distal to the
fragment ceases, resulting in infarction of distal brain tissue due to lack of
nutrients and oxygen.
As a cause of stroke, embolism accounts for approximately 32% of cases.
 Etiology Non Hemorrhage stroke

• Large Vessel Disease

– Cardioembolic
– Atherosclerosis
• Small Vessel Disease
– Lacunar Infarction
• Cryptogenic  Patent Foramen Ovale
 Etiology Hemorrhage stroke

• Primary • Secondary
– Chronic hypertension – Vascular Malformations
– Cerebral amyloid – Aneurysms
angiopathy – Tumors
– Anticoagulant/ – Hemorrhagic transformation
fibrinolytic use of cerebral infarction
– Venous infarction with
– Antiplatelet use
hemorrhage secondary to
– Drug use cerebral venous thrombosis
– Other bleeding – Moya Moya disease
diathesis
 Genetic Cause Of Stroke
• Hemorrhage
• Thrombotic/Embolic Stroke – Factor VIII deficiency
– Homocystinuria or elevated – Factor IX deficiency
homocysteine levels – Factor XI deficiency
– Fabry disease – Familial intracranial aneurysm
– Fibromuscular dysplasia – Sickle cell disease
– Procoagulopathies – Familial cavernous angioma
– Glanzmann thrombasthenia
– Sickle cell anemia – X linked thrombocytopenia

• Rare Monogenic Disorders

• Unknown Mechanism
– Familial porencephaly
– Organic acidemia
– Mitochondrial disorders
– APP,CST3,BRI genes (Autosomal
dominant amyloid angiopathies)
– NOTCH3 gene(Cerebral Autosomal
Dominant Arteriopathy With Subcortical
Infarcts and Leukoencephalopathy)
– KRITI gene (Cavernous angiomas)
 Infark vs Hemoragik
Infarct
Often history of transient ischemic attack
Often onset at rest
Minimal cranial discomfort (often none)
Focal neurologic deficit increasing in
stepwise fashion, consciousness intact
early
Moderately high blood pressure
(ocassionaly normotensive)
Clear cerebrospinal fluid
CT scan show infarction (often normal)
Intracerebral Hemorrhage
No history of transient ischemic attack
Onset during activity
Headache(Often severe)
Rapidly advancing neurologic (1 to 5 hours),
State of consciousness declining to coma
Severe high blood pressure (ocassionaly
moderately high blood pressure)
Blood in cerebrospinal fluid
CT scan shows hemorrhage
 Diagnostics Sign For Location Of Hemisphere Affected In Ischemic
Stroke

Cortical Subcortical Major

(Cortical Gray (Basal (Both cortical and
Matter,Lobar White Ganglia,Thalamus, subcortical)
Matter) Internal Capsule)

Consciousness Stunned to drowsy Normal Drowsy to stupor

Cognitive (Aphasia,etc) Prominent Absent or Mild Prominent

Articulation Rarely Dysarthria Dysarthria Dysarthria

Visual Fields Defect present Defect rarely Defect present

present
Gaze paresis Common Rare Extremely common

Motor Deficits Usually present Absent or present Prominent

Pattern of motor deficits Face,arm,leg Face,arm,leg Face,arm,leg equally

unequally equally
Sensory deficits Usually present Absent or present Prominent

Pattern of sensory deficits Face,arm,leg Face,arm,leg Face,arm,leg equally

unequally equally
Motor and sensory deficits Usually parallel Usually isolated Usually parallel
 Stroke mimic

• The following four conditions represent 62% of stroke mimics

– Postictal deficit (unrecognized seizure)
– Systemic infection
– Tumour/abscess
– Toxic-metabolic disturbance
• Other mimics
– Bell’s palsy
– Peripheral nerve palsies
– Old stroke
– Confusion
– Head trauma
Stroke lakunar
 MATINYA SEL PADA ISKEMI OTAK
ISKEMI O2+Glukosa↓ ATP ↓ Na-K-ATPase ↓

Na Intraselular Cell swelling

Glutamate release
Depolarisasi
(ekstraselular)

Glutamat Reseptor

Metabotropik Ionotropik

NMDA-R AMPA/KAINATE-R KAINATE-R

L-Arginin
Ca Infux Ca Infux Ca Infux
NO-Sintase, Fosfolipase
NO Protein-kinase C
Ca-calmodulin dependent protein kinase II Cell
Protease, Endonuklese death
Ornitin Dekarboksilase
Santin Oksidase
 Stroke hemoragik fisiological change
Haemorrhage
Effects of blood Release
Increase Vasoconstrictor agen
toxic Intracranial press Serotonin, Prostaglandin,

Global ischemic
Influks Ca+

Influks Ca+ Vasospasme

Necrosis
Focal Ischemic
Neuron
Stroke fisiological change

Back
Home
 Anterior cerebral artery
The anterior cerebral artery (ACA) is one of a
pair of arteries on the brain that supplies
oxygenated blood to most medial portions of the 
frontal lobes and superior medial parietal lobes.
The two anterior cerebral arteries arise from the
internal carotid artery and are part of the 
Circle of Willis.
• The left and right anterior cerebral arteries are
connected by the anterior communicating artery.
 Anterior cerebral artery
Areas supplied by the anterior cerebral artery include: [
• The medial surface of the frontal lobe by the medial
orbito-frontal artery, and parietal lobes
• The anterior four- fifths of the corpus callosum
• Approximately 1 inch of the medial surfaces of
frontal and parietal lobes, next to the 
medial longitudinal fissure
• Anterior portions of the basal ganglia and 
internal capsule
• Olfactory bulb and trac
Back
 Middle cerebral artery
• The middle cerebral artery (MCA) is one of the
three major paired arteries that supply blood to the 
cerebrum. The MCA arises from the internal carotid
 and continues into the lateral sulcus where it then
branches and projects to many parts of the lateral
cerebral cortex. It also supplies blood to the anterior 
temporal lobes and the insular cortices.
• The left and right MCAs rise from trifurcations of the 
internal carotid arteries and thus are connected to
the anterior cerebral arteries and the 
posterior communicating arteries, which connect to
the posterior cerebral arteries.
 Middle cerebral artery
Areas supplied by the middle cerebral artery include:
• The bulk of the lateral surface of the hemisphere; except
for the superior inch of the frontal and parietal lobe (
anterior cerebral artery), and the inferior part of the 
temporal lobe.
• Superior division supplies lateroinferior frontal lobe
(location of Broca's area i.e. language expression)
• Inferior division supplies lateral temporal lobe (location
of Wernicke's area i.e. language comprehension)
• Deep branches supply the basal ganglia as well as the 
internal capsule
Back
 Posterior cerebral artery
• The posterior cerebral artery (PCA) is one of a
pair of blood vessels that supply oxygenated 
blood to the posterior aspect of the brain (
occipital lobe) in human anatomy. It arises near
the intersection of the 
posterior communicating artery and the 
basilar artery and connects with the ipsilateral 
middle cerebral artery (MCA) and 
internal carotid arteryvia the posterior
communicating artery (PCommA).
 Posterior cerebral artery
The cortical branches are:
• Anterior temporal, distributed to the uncus and the anterior part
of the fusiform gyrus
• Posterior temporal, to the fusiform and the inferior temporal
 gyri
• Lateral occipital, which branches into
the anterior, middle and posterior inferior temporal arteries
• Medial occipital, which branches into the:
– Calcarine, to the cuneus and gyrus lingualis and the back part of the
convex surface of the occipital lobe
– Parieto-occipital, to the cuneus and the precuneus
• Splenial, or the posterior pericallosal branch, sometimes 
anastamoses with the anterior cerebral artery (ACA), and may
not be present if the ACA wraps around the corpus callosum
Back
 About TCD
• Doppler spectral waveforms examination
based on hemodynamics(functional), not
provide anatomic information(structural)
• TCD measures the velocity of the blood and
not measure CBF
 Clinical Applications TCD
• Diagnosis of intracranial vascular disease
• Monitoring vasospasm in SAH
• Screening of children with sickle cell disease
• Assesment of intracranial collateral pathway
• Evaluation hemodynamic effect of extracranial
occlusive disease on intracranial disease on
intracranial blood flow
 Clinical Applications TCD
• Intraoperative monitoring
• Detection of cerebral emboli
• Monitoring evolution of cerebral circulatory
arrest
• Documentation of subclavian steal
• Evaluation of the vertebrobasiler system.
• Detection of feeders of AVM
 Clinical Applications TCD
Monitoring for
• Coagulation regimens(trombolytic theraphy)
• After head trauma
• During neurologic interventions

Testing of funtional reserve

 TCD, MRA and MRI in acute cerebral ischemia
A. V. Razumovsky 1 , J. H. Gillard 2 , R. N. Bryan 2 , D. F. Hanley 1 , S. M. Oppenheimer 1   1 Department of Neurology, Baltimore. MD. USA   2 Division of Neuroradiology. The Johns
Hopkins Medical Institutions. Baltimore. MD. USA

• TCD showed a sensitivity of 96% and a specificity of 33% for recognizing

abnormal cerebral blood flow velocities. MRA showed a sensitivity of 46%
and a specificity of 75% for assessing intracranial vascular anatomy, while
initial MRI revealed a sensitivity of 84% and a specificity of 100% for
evaluation of ischemic parenchymal changes. Conclusion - Our results
revealed that TCD is an accurate indicator of blood flow status and
correlated well with MRI, MRA abnormalities in acute stroke.

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 Nilai normal

• aPTT (activated partial thromboplastin time)

Normally 20 to 36 seconds

• Normal PT  9.6 - 11.8

• Normal INR  1.3 - 2.0

• D dimer  0-300 ng/ml
• INR and Stroke Prevention
                                                             
• INR stands for International Normalized Ratio.  This
value is a measure of how long it takes your blood to
clot.  While taking warfarin, your blood will be checked
often to see if your INR is within your “target” range.
•  
• INR values:
• 1    =    Normal bleeding time, not on warfarin
• 2.0-3.0 =    Target range for many medical conditions. 
This is a safe range with little or no bleeding risks for
most patients.
• 2.5-3.5   =    Higher target range used for some medical
conditions, such as mechanical heart valves.
• 4.0 and above  =    Increased risk of bleeding.

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Anatomi

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 Modified Ranking Scale (mRS)

The scale runs from 0-6, running from perfect health without symptoms to DEATH.

0 - No symptoms.
1 - No significant disability. Able to carry out all usual activities, despite some
symptoms.
2 - Slight disability. Able to look after own affairs without assistance, but unable to
carry out all previous activities.
3 - Moderate disability. Requires some help, but able to walk unassisted.
4 - Moderately severe disability. Unable to attend to own bodily needs without
assistance, and unable to walk unassisted.
5 - Severe disability. Requires constant nursing care and attention, bedridden,
incontinent.
6 - Dead.

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 National Institutes of Health Stroke Scale
1a. Level of Consciousness (LOC): tests stimulation. Graded from 0-3.
1b. LOC Questions: tests the patient's ability to answer questions correctly.
Graded from 0-2.
1c. LOC Commands: tests the patient's ability to perform tasks correctly. Graded
from 0-2.
2. Best Gaze: tests horizontal eye movements. Graded from 0-2.
3. Visual: tests visual fields. Graded from 0-3.
4. Facial Palsy: tests the patient's ability to move facial muscles. Graded from 0-
5. Motor Arm: tests motor abilities of the arms. Graded from 0-4.
6. Motor Leg: tests motor abilities of the legs. Graded from 0-4.
7. Limb Ataxia: tests coordination of muscle movements. Graded from 0-2.
8. Sensory: tests sensation of the face, arms, and legs. Graded from 0-2.
9. Best Language: tests the patient's comprehension and communication.
Graded from 0-3.
10. Dysarthria: tests the patient's speech. Graded from 0-2.
11. Extinction and Inattention: tests patient's recognition of self. Graded from 0-2.
 NIHSS and Outcome Prediction

• NIHSS below 12-14 will have an 80% good

or excellent outcome.
• NIHSS above 20-26 will have less than a
20% good or excellent outcome.
• Lacunar infarct patients had the best
outcomes.

• Adams HP Neurology 1999;53:126-131

• Baseline NIH Stroke Scale score strongly predicts outcome after stroke
(TOAST)
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Back
EDEM SEREBRI
Cerebral oedema This is an abnormal accumulation of fluid
in the cerebral parenchyma.It is usually the result of
breakdown of the blood–brain barrier, and it may occur
following damage initiated by several different
causes:Ischaemia, e.g. from infarction.Trauma,e.g.
from head injury.Inflammation encephalitis or meningitis.
Oveproduction of CSF by choroid plexus neoplasms
 Edem serebri vasogenik merupakan akibat primer dari
meningkatnya permeabilitas blood brain barier

Edem serebri sitotoksik terjadi sekunder dari kerusakan

elemen seluler serebri, terlepasnya faktor-faktor toksik
dari netrofil dan bakteri. Sehingga terjadi peningkatan
kandungan air intraseluler, dimana terjadi kebocoran
potasium, glukosa digunakan melalui glikolisis
anaerobik, produksi laktat.

Edem serebri interstitial terjadi sekunder dari obstruksi

aliran LCS akibat inflamasi ruang subarakhnoid, seperti
hidrosefalus.
 EDEMA CEREBRI PADA TUMOR

• Vasogenic edema
- Increased permeability of the capillary
endotelial cells plasma protein enter the
extracellular space
- Defect of the endothelial cell junction
- Microvascular transudative factors
*protease released by tumor cells
weakening BBB
CORTICOSTEROID
• Primarily to treat vasogenic
cerebral edema
• Effective in tumors, meningitis,
other cerebral lesion that increase
BBB permeability
 CORTICOSTEROID
• Reduction in peritumor edema :
• decreased endothelial cell permeability by
stabilizing the endothelial cell membrane
• Increased clearance or resolution of cerebral
edema
• Inhibition of tumor cell growth
• Initial: 10mg IV  4mg / 6 hours

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