Stroke.

Tinjauan umum untuk memperluas wawasan.

Dipersiapkan untuk FK.WM

Gunawan Budiarto.

2014

9/28/2014 FK.UWM 1

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.

9/28/2014 FK.UWM 7

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.

9/28/2014 FK.UWM 8

Gejala stroke-2.

• Gejala stroke merupakan manifestasi klinis yang mencerminkan fungsibagian otak yang terkena: serebrum, serebelum, pons, dan sebagainya: dengan menguasai anatomi lokasi dapat ditentukan.

• Lesi yang di batang otak relatif lebih berbahaya dengan yang letaknyalain.

• Perdarahan pada fossa posterior: serebelum, pons cepat berakibatburuk/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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Area of infarct.,may be due to an embolic

infarct

Note the much smaller size of

the left ventricle due to edema

L R

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May need appropriate

measures to decrease brain

edema

CT-image of infarct

Subarachnoid bleeding

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Bleeding

streaks can be

seen, filling the

subarachnoid

space : black

arrow.

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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 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.

Mengapa pembuluh darah otak

bisa pecah dan buntu?

• Sifat pembuluh darah otak yang unik: struktur dinding yang relatiftipis, cara bercabangnya, sifatnya sebagai “endarteries”, input darah ke otak sangat besar dibanding dengan organ lain: 20% dariseluruh curah jantung, padahal berat otak hanya sekitar 5% dariberat 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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* 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

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Berat badan dalam kilogram dibagi perkalian tinggi badan dalam meter.

BB/TB x TB.

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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Ischemic stroke: the risk factors.

Non modifiable risk factors

Age

Race

Gender

Family history of stroke.

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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 Arterial hypertension

• Gender Diabetes mellitus

• Race/ethnicity Transient ischemic attacks

• Family history Prior stroke.

• Genetics 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. 20049/28/2014 FK.UWM 22

Complete list.

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, setaradengan negara lain!

(riset lama oleh mahasiswa farmasi Ubaya)

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Apa yang disebut hipertensi?

• Menurut konsensus, hipertensi adalah bila tensi padabeberapa 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 memperkecilkemungkinan terjadinya komplikasi seperti stroke danserangan jantung.

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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 makinmenipis dan pecah.

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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%.

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* National institute of health stroke scale

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 CT-scan without waiting order by attending doctor!.

9/28/2014 FK.UWM 32

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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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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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.

9/28/2014 FK.UWM 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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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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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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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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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.

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ACEI: angiotensin converting enzyme inhibitor. BB= betablocker

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

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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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 it’s function.

• The concept of hyperacute stroke treatment is based upon this principle.

9/28/2014 FK.UWM 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,

9/28/2014 FK.UWM 47

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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When things are normal-2….

• Cerebral blood flow comes from several sources:

a. the 2 carotid arteries, left and right.

b. the vertebral arteries, left and right, uniting

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 normal…3• 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

Shades of tissue damage.

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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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9/28/2014 FK.UWM 54

Red

infarct

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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9/28/2014 FK.UWM 56

Intra cerebellar

bleeding: 10%.

Small infra-tentorial

space: rapid

increase in ICP.

9/28/2014 FK.UWM 57

Large intra

pontine

hemorrhage

Poor prognosis!

Surgical

intervention is often

not possible

Subarachnoid bleeding

9/28/2014 FK.UWM 58

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

Perfusion weighted MRI, 35 minutes after onset, left. Apparent diffusion co-efficient, same time, right.

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Cerebral hemorrhage.

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

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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.

Note the much smaller

size of the left ventricle

due to edema

L R

9/28/2014 FK.UWM 63

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)

AF cardiogenic thrombi ischaemic stroke

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Endothelial injury

Hypercoagulable state

Circulatorystasis

1. Watson T et al. Lancet 2009;373:155–166; 2. Virchow RLK. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin. Frankfurt,

Meidinger Sohn & Co., 1856. In, Virchow RLK. Thrombosis and emboli (1846–1856); 3. Wolfe 2007.

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

Virchow’s triad for thrombogenesis1,2

• 85% of all strokes are ischaemic in origin3,4

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ECG of atrial fibrillation (top) and sinus rhythm

(bottom). The purple arrow indicates a P wave,

which is lost in atrial fibrillation.

Atrial fibrillation

.

9/28/2014 FK.UWM 67

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 15–20% of all strokes5

1. Hart RG. N Engl J Med 2003;349:1019–1016; 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;114:700–752; 4. Wolf PA et al. Stroke 1991;22:983–988; 5. Lloyd-Jones DM et al. Circulation 2004;110:1042–1046

The new Oral anticogulantsin 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 р-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; 365:981-992.

• 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

9/28/2014 FK.UWM 72Wolf PA et al. Stroke 1991;22:983–988

2-y

ear

ag

e-a

dju

ste

d

incid

en

ce o

f str

oke/1

,000

Individuals

with AF

Individuals

without AF

Risk ratio=4.8

p<0.001

0

10

20

30

40

50

60

Framingham Heart Study (N=5,070)

Beberapa kemungkinan komplikasi saatterapi.

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

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

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Variable OR (95% CI) p

AF 1.84 (1.04–3.27) 0.036

Smoking 1.87 (1.07–3.27) 0.028

Coronary heart disease 1.74 (0.98–3.08) 0.061

Lin HJ et al. Stroke 1996;27:1760–1764

Framingham Heart Study

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Treatment Goals and Strategies for stroke + AF

Maintenance of SR

Pharmacologic

Stroke prevention

Nonpharmacologic

Class IAb

Class IC

Class III

-blocker

Catheter ablation

Pacing

Surgery

Implantable devices

Pharmacologic• Warfarin

• Aspirin

• Xa inhibitor

Nonpharmacologic• Removal/isolation

LA appendage

Rate control

Pharmacologic• Ca2+ blockers

• -blockers

• Digitalis

• Amiodarone

• Dronedaronea

Nonpharmacologic• Ablate and pace

Prevent RemodelingCCB

ACE-I, ARB

Statins

Fish oil

a Only in patients with nonpermanent AF; b the

antiarrhythmic drug classes are based on the

Vaughan Williams classification.

Cryptogenic strokes may often be explained by undiagnosed AF

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Lacunar infarcts (small vessel)15–20%

Intracranial and extracranial

(large vessel)10–24%

Cardiac embolism20–30%

Cryptogenic20–40%*

Other~5%

1. Adams HP et al. Stroke 1993;24:35–41; 2. Camm AJ et al. Eur Heart J 2010;31:2369–2429. 3. Northwest Geriatric

Education Center. http://depts.washington.edu/nwgec/Educational_Resources/stroke_module.pdf. Accessed July 2011

*Consistent with the estimated prevalence of undiagnosed AF

Undetected

paroxysmal

AF?

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

Modified

Rankin scale

grade

Level of

disability

0 No symptoms

1 No significant

disability

2 Slight disability

3 Moderate

disability

4 Moderately

severe disability

5 Severe disability

6 Deadvan Swieten JC et al. Stroke 1988;19:604–607

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 Index3–5

• 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

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1. Scandinavian Stroke Study Group. Stroke 1985;16:885–890; 2. Lindenström E et al. Cerebrovasc Dis 1991;1:103–107;

3. Granger CV et al. Arch Phys Med Rehabil 1979;60:14–17; 4. Mahoney FI and Barthel DW. Md State Med J

1965;14:61–65; 5. The Internet Stroke Center. http://www.strokecenter.org/trials/scales/barthel.html. Accessed July 2011

Assessing stroke severity: National Institutes of Health Stroke Scale

Item Test Score

1a LOC: tests stimulation 0–3

1b LOC questions: tests the patient's ability to answer questions correctly 0–2

1c LOC commands: tests the patient's ability to perform tasks correctly 0–2

2 Best gaze: tests horizontal eye movements 0–2

3 Visual: tests visual fields 0–3

4 Facial palsy: tests the patient's ability to move facial muscles 0–3

5 Motor arm: tests motor abilities of the arms 0–4

6 Motor leg: tests motor abilities of the legs 0–4

7 Limb ataxia: tests coordination of muscle movements 0–2

8 Sensory: tests sensation of the face, arms, and legs 0–2

9 Best language: tests the patient's comprehension and communication 0–3

10 Dysarthria: tests the patient's speech 0–2

11 Extinction and inattention: tests patient's recognition of self 0–2

9/28/2014 FK.UWM 79Brott T et al. Stroke 1989;20:864–870

Scores range from 0 to 42. Patients are given more points for greater deficiencies.

A score of 0 equals normal function

CHADS2 risk stratification for stroke prevention in patients with AF

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• Congestive heart failure+1

• Hypertension +1

• Age ≥75 years +1

• Diabetes mellitus +1

• Prior Stroke or TIA +2

• 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

Risk category Score

Low 0

Intermediate 1

Moderate to high ≥2

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.

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-tPAharus 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

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• Congestive heart failure +1• Hypertension +1

• Age ≥75 years +1

• Diabetes mellitus +1

• Prior Stroke or TIA +2

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

Risk category Score

Low 0

Intermediate 1

Moderate to high ≥2

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.

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 patient’s 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.

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Dash: dietary approaches to stop hypertension.

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 co-administration 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

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..

Increased risk vs general population (%)

Original event Myocardial infarction Stroke

Myocardial infarction

Stroke

Peripheral arterial disease

5–7 x greater risk1

(includes death)3–4 x greater risk2

(includes TIA)

2–3 x greater risk2

(includes angina and

sudden death*)

9 x greater risk3

4 x greater risk4

(includes only fatal MI

and other CHD death†)

2–3 x greater risk3

(includes TIA)

Risk of a second vascular event

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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 hyper-osmolar 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 patient’s 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.

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penumbra

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. Hypertension

2. Smoking

3. Waist hip ratio (tertile 2 vs tertile 1)*

4. Dietary risk score (tertile 2 vs tertile 1)

5. Regular physical activity

6. Diabetes

7. Alcohol intake

8. Cardiac causes

9. Ratio of apolipoprotein B to A1 (tertile 2 vs tertile 1)

10. Psychological factors: stress and depressionO’Donnel et al. Risk factors for ischemic & intra-cerebral

hemorrhagic stroke in 32 countries. Lancet 2010; DOI:10.1016

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

At the end of three months, patient given r-tPA were 30%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 patient’s 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

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.

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

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The narrow

portion of this

aneurysm is

the ideal spot

for clipping

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.

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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Normal

Fatty streak

Lipid rich plaque

Complex plaque

Thrombus

Lipid core

Fibrous capFoam cells

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Development of Atherosclerotic Plaques

It all begins with endothelial

dysfunction: an inflammation!

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 metallo-proteinases 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

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National Institute of Neurological Disorders and Stroke, 2002.

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.

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150

Sid Shah, Pathophysiology of stroke

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

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Lacunar infarcts (small vessel)15–20%

Intracranial and extracranial

(large vessel)10–24%

Cardiac embolism20–30%

Cryptogenic 20–40%*

Other~5%

1. Adams HP et al. Stroke 1993;24:35–41; 2. Camm AJ et al. Eur Heart J 2010;31:2369–2429; 3. Northwest Geriatric

Education Centre. http://depts.washington.edu/nwgec/Educational_Resources/stroke_module.pdf. Accessed July 2011

*Consistent with the estimated prevalence of undiagnosed AF.