Professional Documents
Culture Documents
2014
9/28/2014
FK.UWM
9/28/2014
FK.UWM
9/28/2014
FK.UWM
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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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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CT-image of infarct
Area of infarct.,
may be due to an embolic
infarct
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Subarachnoid bleeding
Bleeding
streaks can be
seen, filling the
subarachnoid
space : black
arrow.
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Intra cerebellar
bleeding: 10%.
Small infra-tentorial
space: rapid increase
in ICP.
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* Waist-hip ratio
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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.
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Age
Race
Gender
Family history of stroke.
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Age
Gender
Race/ethnicity
Family history
Genetics
Complete list.
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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
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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!
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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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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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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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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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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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no stroke.
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Red
infarct
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Intra cerebellar
bleeding: 10%.
Small infra-tentorial
space: rapid
increase in ICP.
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Large intra
pontine
hemorrhage
Poor prognosis!
Surgical
intervention is often
not possible
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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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Cerebral hemorrhage.
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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.
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AF cardiogenic thrombi
ischaemic stroke
Virchows triad for thrombogenesis1,2
Circulatory
stasis
Endothelial
injury
Hypercoagulable
state
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
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
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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.
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Oral anticoagulants-3.
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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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OR (95% CI)
AF
1.84 (1.043.27)
0.036
Smoking
1.87 (1.073.27)
0.028
1.74 (0.983.08)
0.061
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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
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Cardiac embolism
2030%
Cryptogenic
2040%*
Other
Undetected
paroxysmal
AF?
~5%
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
Modified
Rankin scale
grade
Level of
disability
No symptoms
No significant
disability
Slight disability
Moderate
disability
Moderately
severe disability
Severe disability
Dead
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
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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Test
Score
1a
03
1b
02
1c
02
02
03
03
04
04
02
02
03
10
02
11
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
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Risk category
Score
Low
Intermediate
Moderate to high
1 or 2 points are assigned as shown for each of the risk factors above
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*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary
cohorts may vary from these estimates.
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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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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
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*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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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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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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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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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).
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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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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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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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3..
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
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23 x greater risk3
(includes TIA)
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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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Coagulation necrosis.
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Embolism
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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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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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r-tPA
30%
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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.
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may
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Clipping of an aneurysm
A simplified
drawing of
an aneurysm
clip
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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%!
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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.
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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 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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Fatty streak
Foam cells
Complex plaque
Lipid core
Thrombus
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an inflammatory
endothelial response.
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Hemorrhagic stroke
Recurrent stroke
~ 25% of people who recover from 1st stroke will have another one
within 5 years
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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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