Stroke.

Tinjauan umum untuk memperluas wawasan.

Dipersiapkan untuk FK.WM

Gunawan Budiarto.

2014

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FK.UWM

Apa Stroke itu?

Stroke terjadi karena gangguan suplai darah ke otak secara tiba
tiba. Ini menimbulkan serangkaian gejala seperti kelumpuhan,
kesulitan berbicara, penurunan kesadaran, dan sebagainya.
(tergantung lokasi)
stroke = pukulan: terjadi mendadak.
Istilah lain: CVA = cerebro vascular accident.
Istilah dalam Bahasa Indonesia: Gangguan Peredaran Darah Otak
(GPDO).
GPDO merupakan suatu kedaruratan medik!

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Four short stories-1

A sixty year old man woke up with inability to move his left arm and
legs.
He was able to speak and felt no pain.
Past history includes hypertension, smoking and tendency to overeat.
His BMI is 30.*
The E.R. doctor diagnosed stroke and immediately ordered some tests,
including head imaging and some blood tests. He also alerted the
Stroke Team

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Short story-2
A 35 year old woman was brought to the E.R with inability to speak and
weakness of her right arm and leg.
Blood pressure was 130/80 mm. Hg, but her pulse was irregular. ECG
showed atrial fibrillation (AF).
Head CT was normal but an MRI showed an infarction in the territory
of the left middle cerebral artery.

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Short story-3
An obese 60 year old, hypertensive man became acutely ill and vomited
right after an emotional outburst in his office.
He rapidly became unconscious. His eyes looked to the left and there
was no movement on his right extremity.
Blood pressure was 220/130 mm. Hg.
A head CT that was done immediately after arrival in the ER showed a
large intra cerebral bleeding in the left hemisphere of the brain.

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Short story-4.
A forty year old man was suddenly suffering from an intense headache
while working in his office.
He remained conscious but vomited repeatedly and said he had a very
severe headache.
Examination in the ER: patient was still able to respond to questions but
tend to close his eyes. Head movement induced more intense vomiting
and there was a neck stiffness.
A head CT confirmed the diagnosis of a SAH.

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Four stories, each describing the different

stroke types.
1. Cerebral infarct/non hemorrhagic stroke, usually the result of
accumulating risk factors + hypertension that may have been going on
for a long time.
2. Embolic stroke, usually from a cardiac or extra cardiac source.
Abnormality in cardiac rhythm such as AF is common.
3. Cerebral bleeding, usually resulting from poorly controlled
hypertension.
4. Subarachnoid bleed, from a ruptured micro-aneurysm, or AVM.

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Apa gejala stroke yang umum?

Pada lokasi yang cukup sering, misalnya stroke pada daerah a. serebri media
kanan:
1. hemiparese/plegi bagian tubuh kiri.
2. asimetri wajah, dengan tetap berfungsinya
otot kening = kelemahan nervus facialis tipe
sentral. Kemampuan berbicara baik karena
kerusakannya bukan pada belah otak dominan.
3. umumnya sensorik masih baik.
4. bila letak proses pada otak kiri/dominan: afasia.

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Gejala stroke-2.
Gejala stroke merupakan manifestasi klinis yang mencerminkan fungsi
bagian otak yang terkena: serebrum, serebelum, pons, dan sebagainya:
dengan menguasai anatomi lokasi dapat ditentukan.
Lesi yang di batang otak relatif lebih berbahaya dengan yang letaknya
lain.
Perdarahan pada fossa posterior: serebelum, pons cepat berakibat
buruk/fatal karena ruang fossa posterior kecil.

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Bagaimana tampak stroke pada

CT-scan?
Tanda panah = daerah otak yang
pembuluh darah yang terbuntu
= Infark/infarct.

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CT-image of infarct
Area of infarct.,
may be due to an embolic
infarct

Note the much smaller size of

the left ventricle due to edema
May need appropriate
measures to decrease brain
edema
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Subarachnoid bleeding

Bleeding
streaks can be
seen, filling the
subarachnoid
space : black
arrow.

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12

Large intra cerebral

bleeding with mass
effect: midline shift
If accompanied by signs
of increased ICP may
need neurosurgical
consultation or other
measures to decrease
ICP

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Intra cerebellar
bleeding: 10%.

Small infra-tentorial
space: rapid increase
in ICP.

Akibat buruknya: kenaikan tekanan intrakranial.

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Mengapa pembuluh darah otak

bisa pecah dan buntu?
Sifat pembuluh darah otak yang unik: struktur dinding yang relatif
tipis, cara bercabangnya, sifatnya sebagai endarteries, input
darah ke otak sangat besar dibanding dengan organ lain: 20% dari
seluruh curah jantung, padahal berat otak hanya sekitar 5% dari
berat tubuh!
Dimulai dengan gangguan pada lapisan terdalam dari pembuluh
darah otak: kerusakan minimal pada endotil unsur unsur dalam
darah menempel ditempat ini, terjadi penebalan dan akhirnya
buntu.

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15

* Waist-hip ratio

Measurement of waist-hip ratio:

1. In a lean person waist can be measured at its narrowest point, and
hip at its widest portion of the buttocks.
2. In a person with convex waist: one inch above the navel and at the
greater trochanter.

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* Body mass index

This is a simplified version of how to determine whether you are
average, obese, or skinny.
The formula is:
Weight in kilo
Height in meters x height in meters.

Example: body weight is 73 kg. Body height 1.72 m. BMI = 25 : normal

Berat badan dalam kilogram dibagi perkalian tinggi badan dalam meter.
BB/TB x TB.
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Outline of Topics.
The risk factors.
Rapid diagnosis of acute stroke.
Summary of acute phase management.
Drug therapy for acute ischemic stroke.
Clopidogrel: alone or combined with ASA?
Side effects: how to minimize it?
Compliance and persistence.
Conclusions.

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Definition:
Stroke is an acute neurologic injury when blood supply to a part of the
brain is interrupted, either by a clot or rupture of an artery.

Stroke is a true medical emergency.

Stroke is the third (or second) cause of death and disability in the world.

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19

Ischemic stroke: the risk factors.

Non modifiable risk factors

Age
Race
Gender
Family history of stroke.

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20

Ischemic Stroke -2.

Risk factors: (modifiable, treatable)

hypertension
# atrial fibrillation
diabetes mellitus
# hyperhomocysteinemia
hyperlipidemia
# hypercoagulability
cigarette smoking
# oral contraceptive
Infection: chlamydia, helicobacter, viruses.
prior stroke/TIA
# carotid stenosis
physical inactivity
# alcohol abuse.
(Stroke, February 2001)

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Risk Factors for Ischemic Stroke.

Non-modifiable
Modifiable, Controllable, Treatable
=================================================================

Age
Gender
Race/ethnicity
Family history
Genetics

Complete list.

9/28/2014

Arterial hypertension
Diabetes mellitus
Transient ischemic attacks
Prior stroke.
Asymptomatic carotid bruit/stenosis.
Cardiac disease.
Cigarette smoking
Aortic arch atheromatosis.
Dys lipidemia/lipoprotein abnormalities.
Alcohol consumption
Increased fibrinogen and other hemorrheological changes.
Elevated Homocysteine
Low serum folate.
Chronic infection
Oral contraceptives, phenyl propanololamine and other drugs
Obesity/snoring/sleep apnea. BMI 30 or higher,inactivity.
Neurology in Clinical Practice IV ed. 2004
FK.UWM

22

Berapa banyak ?
Penyakit Pembunuh ketiga di Amerika Serikat.
Di Indonesia terkesan meningkat: RSK tiap tahun naik dengan
sekitar 10%: 360-400-440- 560 (angka dari RSK-Surabaya).
Sebagian besar trombotik: 80% di USA/EROPA, 70% di
Indonesia/Asia Tenggara.
Angka kematian masih cukup tinggi.
Angka dari RSK untuk perdarahan maupun trombotik, setara
dengan negara lain!

(riset lama oleh mahasiswa farmasi Ubaya)

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23

Apa yang disebut hipertensi?

Menurut konsensus, hipertensi adalah bila tensi pada
beberapa kali pengukuran lebih tinggi dari 140/90 mm Hg.
Pada JNC VII batas ini turun jadi 130/85.
Tensi tinggi sesaat mungkin suatu office or white-coat
hypertension. Karena pengaruh suasana saat itu.
Penanganan yang tepat dapat mencegah atau memperkecil
kemungkinan terjadinya komplikasi seperti stroke dan
serangan jantung.

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24

Some Definitions.
Hypertension is present when systolic
blood pressure is > 140 mm Hg and
diastolic pressure is > 90 mm Hg.
JNC VII: 130/85.
Stroke is a rapidly developing clinical signs of focal or global
disturbance of cerebral function lasting 24 hours or longer,
with no apparent cause other than vascular signs.
(abbreviated)

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Mengapa stroke ?
Penyakit tertentu bisa merupakan faktor risiko untuk stroke: hipertensi,
merokok, kencing manis, faktor turunan, usia lanjut, obesitas dan
sebagainya.
Proses dimulai dengan rusaknya endotil, di ikuti dengan melekatnya unsur
unsur darah hingga terjadi penyempitan + buntunya pembuluh darah.
Sebaliknya juga bisa terjadi pelebaran pembuluh darah, dindingnya makin
menipis dan pecah.

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26

How do brain cells die ? -1

Immediate and complete cessation of blood supply: necrosis of brain
cells within minutes.
Incomplete stoppage of vascular supply: penumbra (r-CBF 20-25 ml).
May be reversible if promptly treated and r-CBF restored. Also called
apoptotic cell death.
Mediators of cell death: the calcium influx, acidosis, and production of
free radicals.

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How do brain cells die? -2

When brain fails to generate sufficient ATP, such as after oxygen and
glucose deprivation:
energy failure and loss of ionic gradients.
Glutamate is released, re-uptake processes are impaired, the
excitatory amino acid binds to its post synaptic receptors and
promotes excessive calcium entry and release.
Oxidative stress + free radicals + suicidal apoptotic-like pathways = cell
death.

This is a very simplified version of the dying brain cells.

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Apa saja jenisnya?

Secara sederhana Stroke dapat dibedakan menjadi:
Stroke karena buntunya pembuluh darah = stroke trombotik atau stroke
iskemik, termasuk embolik.
Stroke karena pecahnya pembuluh darah otak = stroke perdarahan atau
stroke hemoragik.
Masing masing kelompok bisa dibagi menjadi beberapa sub-kelompok lain:
lokasi, luas, asal.

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NIHSS.
Score < 5 : only mild neurologic deficit.
Score 6-14: moderate neurologic deficit.
Score 15-24: severe neurologic deficit.
Score > 25: most severe neurologic deficit.
These scores are important in helping decide
which patients should be treated with r-tPA.
Score > 5 but < 25. (+ fulfilling other conditions as outlined in
the protocol).

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NIHSS-2*
NIHSS = an excellent predictor of patient
outcome:
1. score > 16 = strong probability of bad
outcome: death.
2. score of < 6 = good recovery.
3. increase of score by 1 point decreases
the likelihood of good recovery by 17%.
* National institute of health stroke scale
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Rapid diagnosis of stroke.

Within one hour if we want to use r-tPA as
the hyper-acute therapy! Door to needle
time.
Watch out for diseases masquerading as stroke (example:
hypoglycemia).
Mobilize stroke team or relevant doctors immediately.
Ideally all suspected stroke patients should undergo a head CTscan without waiting order by attending doctor!.

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Stroke treatment
In a nutshell:
a) within 4.5 hours: rt-PA. Follow guidelines, no
shortcuts!
b) after golden period no bleeding: start antiplatelets. Treat
all
risk factors especially blood sugar. Use statins when
indicated.
c) if bleeding is absent a loading dose of the antiplatelet
agent clopidogrel (300 mg) can be given orally,
followed by 75 mg/day.
d) anticoagulants, parenteral or oral in case of stroke +
non-valvular AF. (bridging with injectable AC?)
e) various neuro-protectors are popular in Indonesia.
f) bleeding: treatment depends on size/location.
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Concise guide to treatment-1

Non-hemorrhagic stroke:
a. acute phase (30 minutes to 3.5 hours) rapid
screening in patient eligible for r-tPA.
b. set in motion the stroke team!
c. ICU overnight in case r-tPA is given.
d. team approach.
Arrival after the golden period:
a. determine stroke cause.
b. start treatment a.s.a.p.
c. overnight in ICU? HCU? Medical ward?

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34

Guide to treatment-2
Use every possible mean to ensure sufficient blood flow to the brain.
Attend to all risk factors rapidly and safely.
Start early rehabilitation program.
Repeat imaging as needed.
Discharge the patient after condition is stable and the family has been
informed fully how to take care if the patient.
Arrange an at home rehabilitation program
Arrange re-appointment follow up schedule.

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35

Acute phase management-1.

Immediate and complete neurological assessment by a neurologist.
Blood tests.
ASAP CT-scan to rule out bleeding.
Start with appropriate treatment according to universally accepted
acute stroke therapy, including the use of r-tPA.
Admittance to a stroke unit with professionally trained staff would be
best.
Watch out for possible early complications.

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36

Acute stroke treatment- 2.

Stabilize the patient: make sure he/she is getting an optimal supply
of oxygen, fluids and nutrition.
Depending on the time window, start with an appropriate mode of
treatment.
Watch out for any possible complication and treat it vigorously:
electrolyte imbalance, infection, blood sugar, etc.
Start physical therapy as soon as possible.

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37

When to start:
Anti-platelet drugs: as soon as bleeding can be
ruled out.
Drugs for diabetes, dyslipidemia and other risk
factors: start therapy immediately. High blood
glucose is detrimental for stroke!
Antihypertensive drugs: after the acute phase,
usually in second week: start low and go slow,
(exceptions may exist!).
Vigorous antihypertensive therapy during this
phase may be counterproductive.

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38

What about those laboratory results?

Platelet aggregation test: perhaps too much
weight has been put to this test: no definite or
straight-forward correlation between TAT* and
severity of stroke.
Homocysteine: still controversial: but treatment is
cheap and easy: why not?
Fibrinogen and CRP: better treat accordingly.
Special tests may be needed for special
situations.
* Test Agregasi Trombosit
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Hypertension and Stroke.

Chronic hypertension is undoubtedly an important
risk factor for both ischemic, hemorrhagic stroke,
and also subarachnoidal bleeding.
Treatment of mild to moderate hypertension with
proper antihypertensive drugs can prevent and
even reverse the athero-thrombotic changes that
are associated with stroke.
Avoid drugs that may induce decrease in CBF.
Avoid treating hypertension occasionally.
On-off therapy is wrong.
Endothelial damage is the initial event.
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40

Acute thrombotic stroke.

The formation of an atherothrombotic
plaque is a long and chronic process
lasting over many years.
Clinical manifestations occur acutely, as
a result of breakdown and activation of
an atherothrombotic plaque: stroke can
be defined as an acute on chronic
process.

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41

JNC-7 classification of BP.

Optimal: < 120/ < 80 mm Hg.
Normal : < 130/ < 85
High normal: 130-139 systolic / 85-89 mmHg diastolic.
Hypertension:

stage 1: 140-159 systolic or 90-99 diastolic

stage 2: 160-179 systolic or 100-109 diastolic
stage 3: > 180 systolic or > 110 diastolic.

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JNC-7 treatment recommendations for

hypertension.

Normal BP: encourage life-style modification.

Pre-hypertension: no treatment except when
compelling indications exist.
Stage 1: thiazide type diuretics for most. May consider
ACEI, ARB, BB, CCB, or combination.
Stage 2: two drug combination for most, usually
thiazide type diuretic and ACEI or ARB or BB or CCB.
Drugs for the compelling indications as needed.
ACEI: angiotensin converting enzyme inhibitor. BB= betablocker

ARB:angiotensin receptor blocker. CCB: calcium channel blocker.

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The threat of hyperglycemia in CVA.

Must be dealt with immediately!
Use of diet and OAD alone may be too slow.
Use of intravenous insulin is appropriate in
the very early stages of stroke.
Target blood glucose: 120-140 mg/dL.
Nursing staff must be vigilant in case
hypoglycemia occur.
An endocrinologist may be needed.

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44

Salvaging the penumbra.

May be achieved if perfusion is quickly restored.
Maintain ideal blood pressure! In the acute phase,
do not lower BP. unless absolutely unavoidable.
Attempts to restore blood flow may be done by the
use of hemo-rrheologically active drugs,
such as pentoxyfyllin.
An ideal neuro-protective drug is still elusive at
this time.

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The concept of ischemic

penumbra.
An area of brain tissue within and around of a central core of dense
ischemic brain tissue which contains electrically inexcitable but
essentially viable cells.
Quick reperfusion, perhaps also by the use of neuro-protective drugs
may prevent further damage and restore its function.
The concept of hyperacute stroke treatment is based upon this principle.

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46

The ischemic penumbra -2.

The central core is un-salvageable, its size will
increase as minutes go by.
The aim of therapy is to start as quick as
possible and stop progressive worsening.
Time window is 4.5 hours.
The stroke team is formed with the aim of
shortening this time window,

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When things are normal.

Endothelial cells are smooth, negatively
charged and repel adhesion of the also
negatively charged platelets.
Luminal surface of endothelial cells are rich in
heparin sulfate proteoglycans that activate
anti-thrombin-III, a natural plasma inhibitor of
thrombin.
Endothelial cells secrete antiplatelet
substances with vasodilatory properties:
prostacyclin and nitric-oxide.

no stroke.
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48

When things are normal-2.

Cerebral blood flow comes from several sources:

carotid arteries, left and right.

b. the vertebral arteries, left and right, uniting
a. the 2

to form the basilar artery.

c. all supplying arteries form an anastomosis at
the skull base: circulus arteriosus Wilissi .

This anastomosis is important part to make sure enough blood

is supplied to the brain.

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When things are normal3

An average of 60-100 ml of blood to each 100 gram of brain
tissue/minute.
When reduced suddenly, signs of insufficiency appear. This become
permanent if blood flow is not restored quickly:
50% of normal = moderate ischemia,
below 20 ml/100g/minute: maximal oxygen extraction leading to
irreversible damage if not quickly restored.
Time window/golden period.

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Schematic picture of an ischemic penumbra

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Shades of tissue damage.

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52

Pecah dan buntu.

Walaupun berdinding tipis, pembuluh
darah otak yang mulus adalah kokoh. Pada
percobaan dengan pembuluh darah binatang yang
diameternya sama dengan pembuluh darah otak
manusia, tekana hingga 1500 mm Hg tidak
mengakibatkan pecahnya pembuluh tersebut.
Harus didahului kerusakan lapisan
dalam (= endothelial damage).

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53

Red
infarct

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54

Bagaimana tampak stroke

pada CT-scan?
Tanda panah =
daerah otak yang
pembuluh darah
yang terbuntu.
= Infark/infarct.

Sekali lagi, sekedar reminder. Dilokasitertentu bisa terjadi komplikasi

buruk.

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55

Intra cerebellar
bleeding: 10%.

Small infra-tentorial
space: rapid
increase in ICP.

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56

Large intra
pontine
hemorrhage

Poor prognosis!
Surgical
intervention is often
not possible

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57

Subarachnoid bleeding
Bleeding streaks
can be seen, filling
the subarachnoid
space: black arrow.
SAB is usually
accompanied be
severe headache.

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Causes of SAH.
Bleeding from an arteriovenous
malformation (AVM)
Bleeding disorder
High blood pressure
Head injury
Unknown/idiopathic cause
Use of anticoagulants

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Perfusion weighted MRI, 35 minutes after onset, left.

Apparent diffusion co-efficient, same time, right.

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60

Cerebral hemorrhage.

gambar CT-scan + hasil otopsi (setelah pasien wafat).

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61

Hemorrhagic strokes.
Intracerebral bleeding can take place in several
locations:
1. in the cerebral hemisphere
2. cerebellum.
3. brainstem.
Subarachnoidal bleeding.
Traumatic cerebral bleeding is not discussed.

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Area of infarct.

Note the much smaller

size of the left ventricle
due to edema

Watch out for signs of

increased ICP!
The left ventricle is shifted
across the midline!
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Watershed infarcts Resulting from

hemodynamic Crisis (hypotensive stroke)

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AF cardiogenic thrombi
ischaemic stroke
Virchows triad for thrombogenesis1,2

Circulatory
stasis

Endothelial
injury

Hypercoagulable
state

85% of all strokes are ischaemic in origin3,4

1. Watson T et al. Lancet 2009;373:155166; 2. Virchow RLK. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin. Frankfurt,
Meidinger Sohn & Co., 1856. In, Virchow RLK. Thrombosis and emboli (18461856); 3. Wolfe 2007.
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65
http://www.safestroke.org/Portals/10/FINAL
Burden of Stroke.pdf.
Accessed July 2011; 4.
http://www.theuniversityhospital.com/stroke/types.htm Accessed Jan 2012

Atrial fibrillation

ECG of atrial fibrillation (top) and sinus rhythm

(bottom). The purple arrow indicates a P wave,
which is lost in atrial fibrillation.

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AF and stroke
Stroke is the most serious
consequence of AF1
In patients with AF, blood clots tend
to form in the atria, particularly within
the left atrial appendage, due to
abnormal blood flow and pooling2,3

These clots may embolize to

the brain causing an
ischaemic stroke2
AF increases stroke risk fivefold,4
and is responsible for approximately
1520% of all strokes5

1. Hart RG. N Engl J Med 2003;349:10191016; 2. National Heart Lung and Blood Institute.
http://www.nhlbi.nih.gov/health/dci/Diseases/af/af_signs.html. Accessed July 2011; 3. Fuster V et al. Circulation
2006;114:700752; 4. Wolf PA et al. Stroke 1991;22:983988; 5. Lloyd-Jones DM et al. Circulation 2004;110:10421046

The new Oral anticogulants

in order of its availability
1. Dabigatran: the pro-drug dabigatran etexilate: is rapidly converted (by a
serum esterase) to dabigatran, a direct competitive inhibitor of factor IIa
(thrombin) inhibitor. Bioavailability 6.5%, serum half-life 12-17 hours. Not
metabolized by the CYP34A system, but -glycoprotein inhibitors (such as
verapamil, ketoconazole, amiodarone etc) can increase dabigatran
concentration.
The RE-LY trial, Circ.2011, 123:2363-2372; Circ. 2012; 125:669-676.

PIN-Stroke, Semarang 2012.

69

Oral anticoagulants-2
2. Rivaroxaban: direct factor Xa inhibitor.

Bioavailability 70%,
serum half-life 5-9 hours. Metabolized by CYP34A system, possible
interaction with CYP34A inhibitors or inducers. Clearance: 36% renal,
unchanged, fecal 7%, unchanged.
ROCKET-AF trial, (NEJM. 2011; 365:833-891).
J-ROCKET-AF trial, (Circ. J. 2012 Aug.24; 76 (9): 2104-2111);
+ many other supporting trials.
ROCKET-AF Will be discussed separately by the next speaker.

PIN-Stroke, Semarang 2012.

70

Oral anticoagulants-3.

3. Apixaban: direct, competitive factor Xa inhibitor with 50%

bioavailability. Also metabolized by CYP34A system. Clearance both
renal (25%) and fecal (50%), unchanged.
The AVERROES trial: NEJM. 2011; 364:806-817. NEJM.2011; 365:981992.
5599 patients, non-valvular AF +1 additional risk factor. 5 mg/twice
daily or 2.5 mg/twice daily.
Official approval by the FDA is still pending.

PIN-Stroke, Semarang 2012.

71

Patients with AF have an approximately

fivefold increased risk of ischaemic stroke
Framingham Heart Study (N=5,070)

2-year age-adjusted
incidence of stroke/1,000

60

Risk ratio=4.8
p<0.001

50
40
30
20
10
0
Individuals
without AF

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Individuals
with AF
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Beberapa kemungkinan komplikasi saat

terapi.
Keadaan memburuk dengan cepat:
Bisa karena terjadi perluasan area infark
1. karena edema otak
2. terjadi hemorrhagic transformation.
3. radang paru.
4. gangguan elektrolit/penurunan kadar albumin.
5. gangguan pada fungsi jantung, dll.
Penanganan sesuai dengan jenis komplikasi yang
dijumpai.
Pembuatan CT/MRI mungkin sekali diperlukan untuk
melihat apakah ada perobahan dibanding sebelumnya.
Pemeriksaa laboratorium perlu sering di-ulang untuk
secara cepat mendeteksi perobahan yang terjdi.

AF increases 30-day post-ischaemic stroke mortality

Framingham Heart Study
Variable

OR (95% CI)

AF

1.84 (1.043.27)

0.036

Smoking

1.87 (1.073.27)

0.028

Coronary heart disease

1.74 (0.983.08)

0.061

Multivariate regression model for risk of post-stroke 30 day mortality

Lin HJ et al. Stroke 1996;27:17601764

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Treatment Goals and Strategies for stroke + AF

Rate control

Pharmacologic

Maintenance of SR

Pharmacologic Nonpharmacologic

Ca2+

blockers
-blockers
Digitalis
Amiodarone
Dronedaronea

Nonpharmacologic
Ablate and pace

Prevent Remodeling

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Stroke prevention

Pharmacologic

Class IAb
Class IC
Class III
-blocker

Catheter ablation
Pacing
Surgery
Implantable devices

CCB
ACE-I, ARB
Statins
Fish oil

Warfarin
Aspirin
Xa inhibitor

Nonpharmacologic
Removal/isolation
LA appendage

a Only

in patients with nonpermanent AF; b the

antiarrhythmic drug classes are based on the
Vaughan Williams classification.

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Cryptogenic strokes may often be

explained by undiagnosed AF
Lacunar infarcts (small vessel)
1520%

Intracranial and extracranial

(large vessel)
1024%

Cardiac embolism
2030%

Cryptogenic
2040%*

Other

Undetected
paroxysmal
AF?

~5%

*Consistent with the estimated prevalence of undiagnosed AF

1. Adams
HP et al. Stroke 1993;24:3541; 2. Camm AJ et al.
Eur Heart J 2010;31:23692429. 3. Northwest Geriatric 76
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Education Center. http://depts.washington.edu/nwgec/Educational_Resources/stroke_module.pdf. Accessed July 2011

Assessing stroke severity the modified Rankin

scale

Modified Rankin
scale:
An incremental scale running from
0 to 6
measures the degree
of disability or dependence in
the daily activities of people who
have experienced a stroke

van Swieten JC et al. Stroke 1988;19:604607

Modified
Rankin scale
grade

Level of
disability

No symptoms

No significant
disability

Slight disability

Moderate
disability

Moderately
severe disability

Severe disability

Dead

How to assess stroke severity

Two commonly used scales for assessing stroke severity are the SSS
and the BI of activities of daily living
Scandinavian Stroke Scale1,2
A composite of scores that describe consciousness; eye movement;
severity of paresis (motor power of arms, hands and legs); orientation;
speech; and facial palsy and gait

Lower scores indicate greater neurological impairment

Barthel Index35
Assesses the presence/absence of both faecal and urinary incontinence,
and the need for assistance with basic activities of daily living, such as
grooming, toilet use, walking and dressing

Lower scores indicate greater disability

1. Scandinavian Stroke Study Group. Stroke 1985;16:885890; 2. Lindenstrm E et al. Cerebrovasc Dis 1991;1:103107;
3. Granger CV et al. Arch Phys Med Rehabil 1979;60:1417; 4. Mahoney FI and Barthel DW. Md State Med J
1965;14:6165; 5. The Internet Stroke Center. http://www.strokecenter.org/trials/scales/barthel.html. Accessed July 2011
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Assessing stroke severity:

National Institutes of Health Stroke Scale
Item

Test

Score

1a

LOC: tests stimulation

03

1b

LOC questions: tests the patient's ability to answer questions correctly

02

1c

LOC commands: tests the patient's ability to perform tasks correctly

02

Best gaze: tests horizontal eye movements

02

Visual: tests visual fields

03

Facial palsy: tests the patient's ability to move facial muscles

03

Motor arm: tests motor abilities of the arms

04

Motor leg: tests motor abilities of the legs

04

Limb ataxia: tests coordination of muscle movements

02

Sensory: tests sensation of the face, arms, and legs

02

Best language: tests the patient's comprehension and communication

03

10

Dysarthria: tests the patient's speech

02

11

Extinction and inattention: tests patient's recognition of self

02

Scores range from 0 to 42. Patients are given more points for greater deficiencies.
A score of 0 equals normal function
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Brott T et al. Stroke 1989;20:864870

79

CHADS2 risk stratification for stroke

prevention in patients with AF
Congestive heart failure+1
Hypertension
+1
Age 75 years +1
Diabetes mellitus
+1
Prior Stroke or TIA +2

Risk category

Score

Low

Intermediate

Moderate to high
1 or 2 points are assigned as shown for each of the risk factors above

Stroke risk low, intermediate, high is determined by the cumulative score

Gage BF et al, 2001; Fuster V et al, 2006; Singer DE et al, 2008.

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Risk factor-based point-based scoring

system - CHA2DS2-VASc

*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary
cohorts may vary from these estimates.

Makin besar CHADS-score makin besar risiko

embolic stroke: indikasi pemberian OAC.
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Oral anticoagulants
Yang paling lama digunakan tergolong VKA= vitamin K antagonist:
warfarin, sintrom.
Yang baru termasuk inhibitor terhadap faktor Xa atau IIb.:
dabigatran, rivaroxaban,
Penggunaan warfarin memerlukan kontrol lab yang cukup ketat.
OAC yang baru tidak memerlukan kontrol laboratorium seketat pada
warfarin.

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Apa yang harus dilakukan?

Secepat mungkin ke rumah sakit: stroke adalah suatu kedaruratan medik!
Time is brain!
Apa yang diberikan tergantung dari jenis stroke dan jangka waktu bisa
dimulainya terapi.
Golden period / Therapeutic window : 3-6 jam, untuk pemberian r-tPA
harus sebelum 3 jam.

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Rumah Sakit yang merawat Stroke:

Ada tim dokter/perawat yang biasa
bekerja menangani kasus stroke:
stroke team.
Tersedia fasilitas yang memadai,
- laboratorium, siap 24 jam.
- CT-scan/MRI, siap 24 jam.
Ruang khusus: Stroke-Unit!

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Apa saja yang harus diwaspadai?

Tingkat kesadaran.
Tensi
3-B: breathing, bowel, bladder.
Nutrisi.
Suhu tubuh
Gula darah: makin tinggi otak makin rusak.
Kadar elektrolit.
Lemak.

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Yang boleh dan yang dilarang.

Stroke trombotik: saat akut tidak perlu diturunkan tensinya secara cepat:
akan memperburuk!
Saat itu otoregulasi otak untuk tekanan darah sedang kacau bila tensi
turun aliran darah ikut turun.
Kadar gula tinggi harus cepat diturunkan.
Antibiotika bila perlu diberi sesuai kuman yang ditemukan.

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CHADS2 risk stratification for stroke

prevention in patients with AF
Congestive

heart failure +1

Hypertension
Age 75 years +1
Diabetes mellitus
Prior Stroke or TIA

+1
+1
+2

Risk category

Score

Low

Intermediate

Moderate to high
1 or 2 points are assigned as shown for each of the risk factors above

Stroke risk low, intermediate, high is determined by the cumulative score

Gage BF et al, 2001; Fuster V et al, 2006; Singer DE et al, 2008.

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Risk factor-based point-based scoring

system - CHA2DS2-VASc

*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary
cohorts may vary from these estimates.

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CT or MRI ?
For acute stroke either CT or MRI can be used to help decide whether
the stroke is thrombotic or hemorrhagic. Clinical picture alone must
suffice where the imaging system is not available but beware..
In case of small bleeding both imaging system is very valuable. CT is
much quicker than MRI.
MRI is a more sensitive method for stroke diagnosis but takes a longer
time and is more expensive.

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Apa yang harus di obati?

Untuk mencapai hasil optimal pasien perlu di obati secara cepat dan
paripurna: segala faktor risiko perlu ditangani secara serentak.
Pilih obat yang tepat untuk kurun waktu serta jenis stroke yang
dihadapi.
Waspada terhadap penyulit yang mungkin timbul, atasi secara cepat
dan tuntas.

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Fisioterapi.
Komponen sangat penting pada tim stroke, pada fase
rehabilitasi.
Di Indonesia sering kurang optimal: kurang intensif.
Berperan membesarkan motivasi pasien untuk sembuh.
Perlu orang yang optimis dan bersemangat.
Jangan membohongi pasien.

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Antiplatelets.
The most important antiplatelet drugs are:
Cyclooxygenase inhibitors: aspirin.
Adenosine diphosphate receptor inhibitors:
Clopidogrel and ticlopidine.
Phosphodiesterase inhibitors: Cilostazol.
Glycoprotein IIB/IIIA inhibitors (intravenous only):
Abciximab (ReoPro), Eptifibatide (Integrilin), Tirofiban
(Aggrasat).
Adenosine reuptake inhibitors: dipyridamole.
Triflusal marketed under the name of Grendis (?)
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Bagaimana prognosanya ?
Tidak selalu jelek!
TIA: sembuh 100% dalam waktu singkat. Harus dianggap sebagai
peringatan dini!
Stroke trombotik bila datang cepat prognosa lebih baik. Door to needle
time
Pencegahan serangan stroke berikut sangat tergantung pada kerjasama
baik antara pasien dan dokter: kontrol secara berkala!

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Peran obat pencegah stroke

(primary prevention)

Obat hipertensi: dianjurkan obat yang disamping efek terhadap

tensi juga berperan terhadap endotil pembuluh darah.
Penggunaan aspirin dosis rendah masih kontroversial. (
established pada prevensi sekunder.)
Penurunan kadar lemak sampai batas aman terutama dengan
obat golongan statin yang mempunyai dual action.
Pengendalian diabetes secara sempurna.
Rokok! Pola hidup.

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Clopidogrel.
Alone or in combination with other drug?
The result of MATCH (Management of
ATherothrombosis with Clopidogrel in High-risk
patients) showed that the addition of aspirin to
clopidogrel is associated with a non-significant
difference in reducing major vascular events. The risk
of life-threatening or major bleeding is increased by
the addition of aspirin.
Addition of a statin may be very useful in the quest for
an intelligent solution to stroke prevention.
How long should clopidogrel be used?

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When Clopidogrel may not be enough:

In case of an embolic stroke: an anticoagulant may
be a better choice.
In case of hypercoagulable state caused by e.g.
polycythemia: pentoxyfylin or measures to lower
hemoglobin may be needed.
If studies show carotid stenosis: carotid
endarterectomy or stenting may be useful.
Cardiac arrhythmia such as AF needs proper
management to minimize recurrence.
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Pencegahan stroke.
Perlu dilakukan sejak dini dan konsisten.
Hiduplah dengan teratur, hindari stress.
Ingat bahwa makan bukan tujuan tapi sarana.
Olah raga, hindari rokok, jaga berat badan dsb.
HRT (hormone replacement therapy) akhir akhir ini tidak sepopuler seperti
dulu!.

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Team-work.
Pasien perlu yang terbaik dan dokter bukan superman: perlu tim
stroke.
Biasanya tim stroke terdiri dari:
1. Dokter ahli Saraf.
2. Internist dan/atau ahli peny.jantung.
3. dokter bedah saraf sebagai konsultan
3. Ahli fisioterapi.
4. Dokter dengan keahlian lain dimana
perlu: pulmonologist, endocrinologist,
mungkin juga psikiater.

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When must clopidogrel be stopped?

In case of drug allergy: rare.
Before surgery: one week before the scheduled event. Restart as
soon as possible.
When cost of drug exceeds the patients financial capability.
Some advocate the use of alternate day treatment.

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Conclusions.
Use of clopidogrel in ischemic stroke is both easy
and effective.
Side effects are few and usually mild, and in most
cases preventable.
Combination with low dose aspirin except in special
cases is not accompanied by a significant increase
in efficacy, but side effects are more common. (The
MATCH study).

Some strokes are better treated with other drugs.

Better doctor-patient relationship help in
maintaining optimal care for the stroke patient.
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Trivia that may make a difference.

Water bed.
Albumin.
Electrolytes: should be checked several times.
Hyperosmolar agents.
Antidepressants or tranquilizers.
Prevention of bed sores.
Prevention of opportunistic infections.

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Secondary prevention of stroke.

Treatment of hypertension
Use of antiplatelet agents in most patients.
Use anticoagulant in selected patients.
Treatment of dyslipidemia with statins.
Regulation of diabetes.
Life style modification. Stop smoking.
Reduce obesity.

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Life style modification.

Life-style modification is an important part of the effort to
prevent stroke.
1. maintain ideal body weight.
2. regular/aerobic physical activity 30-45 minutes/day,
daily or 3-4 x/ week.
3. lots of fruit and vegetables, low fat dairy products, reduce
saturated and total fats.
DASH eating plan.
4. limit sodium intake, maintain adequate intake of
dietary potassium: 90 mmol/day, adequate intake of
dietary calcium and magnesium.
5. stop smoking, limit alcohol intake to < 30 ml/day.
Dash: dietary approaches to stop hypertension.
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Doctor-patient relationship.
Maintain good communication.
Spent sufficient time to explain things.
Schedule the next consultation within an appropriate time limit:
asking a post stroke patient to see you every week may not be wise.
Be honest! The patient is not your milking cow! In the long run
fairness pays.

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Adverse effects of clopidogrel.

Severe neutropenia: 5/10.000.
Thrombotic thrombocytopenic purpura/
TTP: 4/1.000.000.
Hemorhage: the incidence of hemorrhage may be increased by the coadministration of aspirin. Gastrointestinal:2%
Cerebral hemorrhage:0.1-0.4%

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How long?
There is no consensus yet about the optimal duration of clopidogrel
therapy.
After placement of coronary artery stents a minimal of six months is
generally accepted, often in combination with aspirin.
Advise the patient to stop medication one week before any surgical
intervention is done.

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How to minimize adverse effects of clopidogrel?

Do a routine blood test, especially during the first
months of therapy.
Tell the patient to report any unpleasant side effects
(mostly gastric), side effects.
Unless absolutely necessary: do not combine
clopidogrel with aspirin. Combination with cilostazol
is also not recommended.
If aspirin is absolutely indicated, give also a proton
pump inhibitor such as esomeprazol.
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Lacunar Stroke:
the lenticulo-striate
arteries.

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Blood clot
stops the flow
of blood to an
area of the
brain

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Pathophysiology at Macro Tissue level.

Cerebral Blood Flow (CBF),
- ischemic thresholds
Ischemic penumbra and Window of
opportunity.
Window of opportunity: also called
golden period, may last up to 4.5 hours.

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Conditions influencing Progression and

Extent of Ischemic injury.
Rate and duration of the ischemic event,
Collateral circulation in involved area.
Systemic circulation and arterial blood
pressure
Coagulation abnormalities
Temperature
Glucose: high blood glucose = bad.

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CBF and Ischemic Thresholds

Normal CBF 50-60 cc/100g/minute, varies in different regions of the
brain
CBF 20-30 cc/100g/min loss of electrical activity.
CBF 10 cc/100g/min Neuronal death.

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3..

Risk of a second vascular event

Increased risk vs general population (%)
Original event

Myocardial infarction

Stroke

Myocardial infarction

57 x greater risk1

34 x greater risk2

(includes death)

(includes TIA)

23 x greater risk2

9 x greater risk3

Stroke

(includes angina and

sudden death*)
Peripheral arterial disease 4 x greater risk4
(includes only fatal MI
and other CHD death)

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23 x greater risk3
(includes TIA)

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Medications often used for treatment of

acute stroke.
Infusion fluids: often needed in the acute phase to supply fluids, as a
vehicle to deliver medications, and so on.
Antibiotics when indicated.
Drugs with unique property to promote blood flow, to provide
neuro-protection?.
Medications to help lower intracranial pressure, usually hyperosmolar fluids.
Others.

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Medications often used for stroke-2.

Antihypertensive drugs: use judiciously. Rapid lowering of BP
especially in the acute phase may be harmful.
Once given, monitor closely for any unwanted side effects.
Medications to regulate blood sugar: may be very useful if given
prudently. Blood sugar level must not be allowed to become too low.
Hyper-osmolar agents: may be life saving but may not be given if
contraindications excist.

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Medications for stroke-3.

Blood and blood products: use prudently.

Sodium, potassium, human albumin, etc.: treat judiciously.
Parenteral nutrition: use when indicated. Delaying nutrition may harm
the patient.
Lipid lowering medications: indicated when presence of dis-lipidemia
may impede recovery.
The use of statins often recommended because of its beneficial
influence towards developing plaques.

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Medications for stroke-4

Regulating blood sugar: high blood sugar in stroke is bad. Lower
blood sugar judiciously, aiming at achieving normal blood glucose.
Use of insulin injections in the acute phase is often necessary.
Electrolyte imbalance may happen is acute stroke. This should be
corrected.
Subnormal albumin level may delay recovery and should also be
corrected.

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Medications for stroke-5

Good nursing care should not be neglected. Pressure sores may easily
happen in bedridden patients. Bladder and bowel function may also
hamper patients recovery. Soiled and wet linen induce bedsores!
Respiratory tract infection may cause trouble because fever is bad for
stroke!
Regular exercise starting from day-1 is not to be forgotten.

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Treatment targets
Blood pressure after acute stage: do not lower it too quickly!
135/85, start low and go slow: after 7-10 days.
Blood glucose: aim at normo-glycemia.
Lipids: aim at achieving NCEP guidelines, first choice statins
Anti-platelets: follow Stroke Guidelines.
Stroke + AF: anti-platelets alone is not sufficient. Give an
anticoagulant!
Obesity: encourage sensible WRP.
Other risk factors have to be treated with appropriate measures.

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Molecular events in stroke

Failure of ionic pumps mitochondrial injury activation of leukocytes
(with release of mediators of inflammation), generation of oxygen radicals, +
release of excitotoxins.
Increased cellular levels of sodium, chloride,and calcium ions resulting in
stimulation of phospholipases and proteases followed by generation and
release of prostaglandins + leukotrienes, breakdown of DNA and the
cytoskeleton.
Breakdown of the cell membrane.

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MRI image of acute stroke

Diffusion and perfusion weighted MRI mismatch.
Perfusion weighted image on the right is larger,
covering the penumbra that may still be
salvageable.
penumbra

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Coagulation necrosis.

A process of cell death that evolves over

6 to 12 hours
Necrotic death is attributed to effects of
physical, chemical and osmotic damage
to the plasma membrane
Morphology of dying cells is distinct
from cells dying from apoptosis.
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Embolism

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Ischemic stroke due to hemodynamic

crisis: hypotensive stroke.
Any event causing abrupt drop in blood pressure results in critical
compromise of CBF and hence cerebral perfusion
Sites affected by critically low CBF are located at the end of arterial
territory, hence the term watershed or boundary zone infarct

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Microcellular Mechanisms of
Neuronal injury.
Development of microcirculatory disturbances
- formation of micro thrombi
- accumulation of noxious metabolites
- interaction of endothelial cells with PMN
leucocytes and platelets.
- PMNs trigger neuronal necrosis.

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10 risk factors accounting for 90% of the risk for

Stroke.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Hypertension
Smoking
Waist hip ratio (tertile 2 vs tertile 1)*
Dietary risk score (tertile 2 vs tertile 1)
Regular physical activity
Diabetes
Alcohol intake
Cardiac causes
Ratio of apolipoprotein B to A1 (tertile 2 vs tertile 1)
Psychological factors: stress and depression
ODonnel et al. Risk factors for ischemic & intra-cerebral
hemorrhagic stroke in 32 countries.
Lancet 2010; DOI:10.1016
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Thrombotic stroke
Atherosclerosis: the commonest pathology of vascular obstruction
leading to thrombosis
Other pathological causes:
- fibro muscular dysplasia
- arteritis (giant cell and Takayasu)
- dissection of vessel wall and hemorrhage
into atheromatous plaque
hypercoaguability

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Selective vulnerability of neurons to

global ischemia
Hippocampus: pyramidal cell layer
Cerebral cortex: Purkinje cell layer
Cerebellar cortex

The increased vulnerability of these neurons is due to abundance of

neurotransmitter glutamate in these neurons.

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r-tPA
30%

At the end of three months, patient given r-tPA were

more likely to have good recovery compared to those given other
treatment.
Symptomatic intra-cerebral bleeding within 36 hours was

6.4%, compared with 0.6 % in patients not given r-tPA.

NEJM, 1995- December.

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Stroke treatment
In a nutshell:
a) within the golden period : rt-PA. Follow guidelines,
no shortcuts!
b) after golden period: start antiplatelets. Treat all risk
factors especially blood sugar. Use statins.
c) if bleeding is absent a loading dose of clopidogrel
(300 mg) can be given orally,
followed by 75 mg/day.
d) anticoagulants, parenteral or oral in case of stroke +
non-valvular AF. (bridging with injectable AC?)
e) various neuro-protectors are very popular in
Indonesia.

Bleeding: treatment depends on size/location.

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Concise guide to treatment-1

Non-hemorrhagic stroke:
a. acute phase (30 minutes to 3.5 hours) rapid screening in patient is
eligible for r-tPA.
b. set in motion the stroke team!
c. ICU in case r-tPA is given.
d. team approach.
Arrival after the golden period:
a. determine stroke cause.
b. start treatment a.s.a.p.
c. overnight in ICU? Medical ward?

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Intra cerebral bleeding

Treatment depends on several factors:
1. location and volume of bleeding.
2. increasing intracranial pressure
3. availability of a qualified neurosurgeon.
4. informed consent from patients family.
Posterior bleeding has the tendency to cause a
rapid increase in intracranial pressure

may

need surgery much sooner.

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Large intra cerebral

bleeding with mass
effect: midline shift
If accompanied by signs of
increased ICP may need
neurosurgical consultation or
measures to decrease ICP

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Clipping of an aneurysm
A simplified
drawing of
an aneurysm
clip

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Perfusion weighted MRI, 35 minutes after onset, left.

Apparent diffusion co-efficient, same time, right.

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Beware!
Global Stroke Burden on the rise in
Younger Adults! Lancet, 23 October 2013
In low income countries: stroke is on the rise,
with higher mortality: 42%!

In higher income countries the reverse is true!

Incidence decrease by 12%, mortality
decrease by 37% in the last two decades.
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Message for
stroke warning
signs.
Developed by
Massachusetts
Dept. of Health
as part of a
public education
program.
Stroke, October 2007.

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An intra-cerebral aneurysm

The narrow
portion of this
aneurysm is
the ideal spot
for clipping

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In a nutshell.
Stroke occurs whenever blood supply to the brain is abruptly
interrupted.
The cause can be:
* thrombotic, including embolic,
* hemorrhagic: bleeding from a ruptured
blood vessel, aneurysm or AVM.

Rapid rescue of the stricken area may to

some extent, reverse the catastrophe.

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The circle
of Willis

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The circle
of Willis

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Vascular
supply of
the brain:
seen from
different
sides.
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The venous system of the brain-1

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The venous system of the brain-2

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The Problem.
Stroke ranks second after ischemic heart disease
as a cause of death worldwide.
Stroke increases exponentially with age.
In Western societies: 80% are caused by focal cerebral ischemia due to
arterial occlusion, 20% are caused by hemorrhages.
In Surabaya, (approximately 550 new cases/year at the Catholic Hospital
Surabaya), 30% are due to hemorrhages.

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Development of Atherosclerotic Plaques

Fatty streak

Lipid rich plaque

Normal
Fibrous cap

Foam cells

Complex plaque
Lipid core
Thrombus

It all begins with endothelial

dysfunction: an inflammation!
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Description of an unstable plaque.

A stable plaque has thick fibrous cap with an extracellular matrix
without a large lipid core and inflammatory cells.
An unstable plaque has a thin fibrous cap, a thrombus at the
shoulder, many inflammatory cells, and a large lipid core.
Inflammation in the plaque leads to release of matrix metalloproteinases which digest collagen and cause thinning of the fibrous
cap.
The necrotic lipid core grows as a result of the accumulation of lipids
in the extracellular matrix, death of lipid laden macrophages, and
accumulation of erythrocytes membranes after intra-plaque
hemorrhage from the vasa vasorum.
Oxygen radicals generated from many sources, including NADPH
oxidase and inflammatory cells, oxidize LDL and cause necrosis of
cells.
Repetitive cycles of plaque rupture and healing produce endothelial
thickening that may finally disrupts blood flow.
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At the very beginning.

Atherothrombosis.
starts with a dysfunction of the endothelial cells
lining the blood vessel that may be induced by:
Chemical,
Mechanical
Immune
Infectious, and many other processes that cause

an inflammatory

endothelial response.

Present consensus regards athero-thrombosis as

a specific response of the endothelial tissue to
various inflammatory stimuli.

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Clinical classification of stroke

Ischemic stroke
Accounts for 80% of all strokes ( Surabaya 1996: 65%)
Can be embolic or thrombotic

Hemorrhagic stroke

Accounts for 20% of all strokes. (Surabaya: 1996, > 30%).

Recurrent stroke
~ 25% of people who recover from 1st stroke will have another one
within 5 years

Transient ischemic attack (TIA)

mini stroke; resolves with no noticeable symptoms or deficits
within 24 hours
National Institute of Neurological Disorders and Stroke, 2002.
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Global ischemia or hypotensive stroke

Profound reduction in systemic blood pressure due to any reason is
responsible for hypotensive stroke.
Neurons located in the pyramidal cell layer of the hippocampus, the
Purkinje cell layer of the cerebellar cortex and the cerebral gray
matter are particularly vulnerable.
Abundance of glutamate in these neurons Make them more
susceptible.

Sid Shah, Pathophysiology of stroke

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Acute ischemic injury.

The occlusion of a large vessel (such as the
MCA) is rarely complete and cerebral blood
flow (CBF) depends on the degree of
obstruction, and collateral circulation.
Many factors influence progression and
extent of injury.

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The main mechanisms of ischaemic

stroke
Lacunar infarcts (small vessel)
1520%

Intracranial and extracranial

(large vessel)
1024%

Cardiac embolism
2030%

Cryptogenic
2040%*

Other
~5%
*Consistent with the estimated prevalence of undiagnosed AF.
1. Adams HP et al. Stroke 1993;24:3541; 2. Camm AJ et al. Eur Heart J 2010;31:23692429; 3. Northwest Geriatric
Education Centre. http://depts.washington.edu/nwgec/Educational_Resources/stroke_module.pdf. Accessed July
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