Patofisiologi dan Penatalaksanaan

Terapi serta Peningkatan Kualitas

Hidup terhadap Pasien Gawat
Darurat Kasus Stroke

Fakhrurrazy
 Curriculum Vitae
• Nama : dr. Fakhrurrazy, M.Kes, Sp.S
• TTL : Banjarmasin, 30 Oktober 1974
• Pendidikan
– Dokter umum, Thn 2000 (FK ULM)
– S2 Fisiologi Saraf, Thn, 2004 (FK UGM)
– Spesialis Saraf, Thn 2013 (FK UGM)
• Pekerjaan
– Kordik Departemen Neurologi FK ULM
– Staf fungsional Penyakit Saraf RSUD Ulin
• Organisasi : IDI, Perdossi
• Status : Kawin, 4 Anak
 Apa itu Stroke ?

Stroke terjadi ketika aliran darah ke otak

dihambat oleh tersumbat atau pecahnya
pembuluh darah otak
 Definisi Stroke
• Stroke (Cerebrovascular accident, CVA): Tanda klinis
berupa gangguan fungsi otak fokal maupun global
yang berkembang cepat, dengan gejala yang menetap
selama 24 jam atau lebih, atau mengakibatkan
kematian, tanpa sebab yang jelas selain berasal dari
vaskular (WHO, 1976)
• Definisi stroke berdasarkan onset:
– Transient ischemia attack (TIA): Kejadian iskemik < 24 jam
tanpa munculnya kelainan neurologis yang menetap
– Stoke in evolution: defisit neurologis yang progresif dari
waktu ke waktu, menunjukkan perluasan area iskemik
– Completed stroke: kejadian iskemik dengan deficit
neurologis yang menetap
 Epidemiology: Global Burden
• 15 juta non-fatal stroke terjadi setiap tahun di dunia
• Penyebab kematian nomor 2  5 juta setiap tahun
• Penyebab utama kecacatan permanen  5 juta
pertahun
• Risiko stroke tergantung umur dan jenis kelamin
• Insidens: bervariasi secara geografi
– 388/100,000 di Russia,
– 247/100,000 di China,
– 61/100,000 di Fruili, Italy
 Tuberculosis Malaria
Diarrhoea
Perinatal causes
2% Other causes
3% 3%
Chronic obstructive pulmonary 4%
disease 27%
5%
HIV/AIDS 5%

Respiratory infections 7%

Coronary heart
disease
9%
Cancer 13%
Accidents Stroke
12%
10%

Since 80s, a significant increase (> 2-fold ) has been noticed in incidence of stoke : 1–
2 /1.000 people in USA, 2–2.5/1.000 in Western and 3–3.5/1.000 in Eastern Europe

American Stroke Association. Heart Disease and Stroke Statistics 2004

 Faktor Resiko
• Kepentingan:
– Mengidentifikasi secara dini mereka
yang berisiko lebih besar terkena
stroke
– Rencana untuk terapi pencegahan
• Dibagi:
– Dapat dimodifikasi
– Tidak dapat dimodifikasi
 Stroke: Faktor resiko tidak dapat
dimodifikasi
• Umur
• Jenis kelamin
• Etnis
• Riwayat stroke
• Keturunan
 Stroke: Faktor Resiko yang dapat
dimodifikasi

• Hipertensi • Sickle cell disease

• Diabetes • Terapi hormone

postmenopausal
• Dislipidemia • Merokok
• Fibrilasi atrium • Nutrisi dan diet
• Asymptomatic carotid • Aktivitas kurang
stenosis • Obesitas
• Kelainan jantung yang
lain
Modifiable Risk Factors: Others
 Perbandingan Faktor Resiko Utama
Penyakit Jantung Koroner dan Stroke

Coronary
Coronary Cerebral
Cerebral

BP
BP SBP,DBP
SBP,DBP SBP,DBP
SBP,DBP

Cholesterol
Cholesterol

HDL
HDL
smoking
smoking

obesity
obesity

Heart
Heart rate
rate
Other
Other factors
factors (viral,
(viral,
infectious
infectious
Two Major Types of Stroke
Major Types of Stroke

Fig. 56-3
 Stroke Subtypes
Hemorrhagic Stroke (17%) Ischemic Stroke (83%)
Atherothrombotic
Cerebrovascular
Intracerebral Disease (20%)
Hemorrhage (59%)
Cryptogenic and
Other Known
Cause (30%)

Subarachnoid Hemorrhage (41%)

Lacunar (25%) Embolism (20%)

Small vessel disease

Albers GW, et al. Chest. 1998;114:683S-698S.

Rosamond WD, et al. Stroke. 1999;30:736-743.
STROKE ISKEMIK
 Stroke Iskemik
• Berasal dari tidak adekuatnya aliran darah ke otak
dikarenakan penyumbatan pembuluh darah
komplit/parsial
• 85% dari semua stroke adalah stroke iskemik
(stroke non hemorrhagic)
• Sebagian besar pasien dengan stroke iskemik
tidak mengalami penurunan kesadaran pada 24
jam pertama
• Gejala memberat mulai 72 jam pertama
diakibatkan edema cerebral
 Apa Penyebab Stroke Iskemik?
• Atherothrombosis
• Embolus:
– Material: merah (kaya fibrin) atau putih (kaya
platelet)
– Sumber: Jantung? Aorta? Carotid Artery?
• Small artery disease
• Hipoperfusi: Hemodynamic
• Others: arterial dissection, arteritis, etc.
 Klasifikasi Stroke Iskemik

• Berdasarkan teritori vaskular

– Sirkulasi anterior: a.carotis
– Sirkulasi posterior: vertebrobasilar
• Berdasarkan etiologi
– Trombotik
– Embolik
 Suplai Darah Otak:
Anterior Circulation
• Internal Carotid A.
– Cabang dari a. carotis
communis
– Cabang: anterior
cerebral, anterior
communicating, middle
cerebral, posterior
communicating
Blood Supply to the Brain:
Posterior Circulation
Circulus Willisi
 Common areas in the brain for stroke

• Middle Cerebral Artery

(MCA)
• 2. Basilar Artery
• 3. Posterior Cerebral
Artery

The deficits the person

experiences is determined by the
LOCATION of the infarct
 Lokasi Lesi dan Klinis
Carotid territory Vertebrobasilar
• Amaurosis fugax • Hemianopia
• Dysphasia • Quadraparesis
• Hemiparesis • Cranial N dysfunction
• Hemi-sensory loss • Cerebellar syndrome
• Crossed deficit
• Loss of consciousness
 Stroke Iskemik Trombotik
• Stroke trombotik
– Thrombosis muncul sehubungan dengan kerusakan
dinding pembuluh darah → blood clot
– Menyebabkan thrombosis atau penyempitan pembuluh
darah
– Penyebab stroke paling banyak
– 2/3 kasus berhubungan dengan hipertensi dan diabetes
– Sering didahului TIA (transient ischemic attack)
 What is a thrombus?
• Is NORMAL in cases of injury

• ABNORMAL :
– a blood clot that forms in a blood vessel
– may be arterial or venous

– Pathological thrombus = THROMBOSIS

• May be caused by fatty deposits that build up in arteries

• Damage to the endotheilum (often r/t poorly controlled HTN) fosters buildup of fatty deposits
and cholesterol
– Body responds to the vessel wall injury by forming plaque which can rupture and form clots
 Normal Arterial Wall
(intima, Media, Adventitia)

Intima:
Endothelium
Internal elastic laminae

Media:
Smooth muscle cell
Lumen
Collagen proteins

External elastic laminae

Endothelial dysfunction in atherosclerosis
(Early changes)

up-regulation of endothelial
adhesion molecules

Leucocyte migration into the arterial wall

Penetration of lipoproteins

greater permeability of the

endothelium

Leucocyte adhesion
Lipid core formation (fatty streak) in atherosclerosis

Platelets’ adhesion and coagulation

Migration of smooth muscle cells

Foam cells formation

T cells activation

Adhesion and penetration of

leucocytes
 Formation of atherosclerotic plaque
(death & rupture of foam cells in fatty streak)

Formation of necrotic core

Accumulation of macrophages

Formation of fibrous cap

Rupture of plaque and thrombus formation (supsequent luminal occlusion)

Intravascular thrombus

Lipid layer

Thrombus inside the plaque

 Progression of atherosclerosis
Threshold

Decades Years-Months Months-Days

Healthy Subclinical Symptomatic

Intima
Lumen
Media

Plaque

Threshold

Thrombus
Intima
Lumen
Media

Plaque

HEALTH
HEALTH POLICY
POLICY PRIMARY
PRIMARY PREVENTION
PREVENTION SECONDARY
SECONDARY PREVENTION
PREVENTION
Diet
Diet and
and lifestyle
lifestyle changes
changes Drug
Drug treatment
treatment Aggressive
Aggressive drug
drug therapy
therapy
 Stroke Iskemik Embolik
• Stroke Embolik
– Embolus lepas, kemudian masuk dan menyumbat arteri
cerebral
– Sebagian besar emboli berasal dari jantung, dimana plak
terlepas dari endokardium kemudian memasuki sirkulasi
darah sistemik
– Berhubungan dengan gejala klinis yang muncul secara tiba-
tiba dan cepat
– Sering berulang kecuali jika penyebabnya dapat diobati
secara adekuat
Atherosclerosis: Hyperlipidemia/High
cholesterol
 Etiologi dan Patofisiologi
• Otak memerlukan suplai O2 dan glukosa
secara terus menerus agar neuron dapat
berfungsi dengan baik
• Jika aliran darah terhambat:
– Metabolisme neurologi berubah dalam 30 detik
– Metabolisme berhenti dalam 2 menit
– Kematian sel otak muncul dalam 5 menit
 TIME
IS BRAIN!
Pada kasus large vessel
acute ischemic stroke…

- 1.9 juta neurons

- 14 miliar sinaps
- 12 km myelinated fibers

Rusak setiap menitnya …

(JL Saver, 2006)
Patofisiologi Ischemic Brain Injury
• Otak:
– 2% dari total massa tubuh manusia
– Menerima 20% darah dari cardiac
output
• Perfusi inadekuat: kematian jaringan dan
deficit fungsional
• Ischemic brain injury:
– The “ ischemic thresholds ”
 Effects of Reduced CBF

Ischemia
Infarction
Penumbra

50 – 55 25 20 15 8

Normal Edema Loss of Na/K+

ml/100g/min electrical pump
↑lactate activity failure; ↓ ATP Cell Death
 Penumbra
ISCHEMIC PENUMBRA: PATHOPHYSIOLOGY
OF THERAPEUTIC WINDOW Core

CEREBRAL Normal
BLOOD 20 function
FLOW
(ml/100g/min) 15
Neuronal CBF
PENUMBRA dysfunction 8-18
10

5 Neuronal CBF
CORE death <8

1 2 3
TIME (hours)

Identification of penumbra through MRI perfusion-diffusion mismatch or

perfusion CT may replace time as the major indication for emergency acute
ischemic stroke therapies.
Patofisiologi Ischemic Brain Injury
• Sekitar area inti dari iskemia adalah batas zona dari
kurangnya aliran darah dimana iskemia masih bisa
reversibel (area penumbra)
• Jika aliran darah adekuat dapat kembali dengan
cepat(< 3 jam),kaskade iskemik dapat berhenti
– Mengurangi kerusakan otak dan mengurangi kehilangan
fungsi neurologis
Patogenesis Stroke Iskemik

Penumbra

Infarction
Ischemic Penumbra: Current Concept
STROKE HEMORRHAGIC
 Stroke Hemorrhagic
• Penyebab dari 15% stroke
• Disebabkan dari pendarahan ke jaringan otak
atau spatium subarachnoid atau ventrikel otak
 Stroke Hemorrhagic
• Intracerebral hemorrhage
– Perdarahan di dalam otak yang disebabkan
rupturnya pembuluh darah
– Hipertensi adalah penyebab utama
– Sering muncul saat beraktivitas
– Gejala muncul secara mendadak dan
berlangsung selama beberapa menit hingga
berjam-jam (selama perdarahan berlangsung)
– Manifestasi klinis: defisit neurologis, nyeri
kepala, penurunan kesadaran, dan hipertensi
 Hemorrhagic Stroke
• Subarachnoid hemorrhage
– Pendarahan di spatium subarachnoidea,
diantara arachnoid mater dan pia mater
– Umumnya disebabkan rupture dari
aneurisma cerebri
 Manifestasi Klinis Stroke

• Mempengaruhi beberapa fungsi tubuh

– Aktivitas motorik
– Eliminasi
– Fungsi intelektual dan kognitif
– Spatial-perceptual alterations
– Personality
– Afek
– Sensasi
– Komunikasi
Fungsi Hemispheres Cerebri

PHOTO: Courtesy of National Stroke Association

Manifestations of Right-Brain and Left-Brain
Stroke

Fig. 56-6
RIGHT sided stroke vs LEFT sided stroke

Hemiparesis vs Hemiplegia

weakness paralysis
 FAST Test
• Use the FAST test for recognizing and responding to
stroke symptoms.
• Facial Droop: Ask the person to smile. Does one side
of the face droop?
• Arm Drif: Ask the person to raise both arms. Does
one arm drift downward?
• Slurred Speech: Ask the person to repeat a simple
sentence. Does the speech sound slurred or strange?
• Time: If you observe any of these signs, it’s time to
call a senior doctor.
CVA Recognition
Assess
 Facial droop
(have patient smile)
 Normal: Both sides of
the face move equally
 Abnormal: One side of
face does not move
as well
Assess
 Arm drift
(have patient hold arms out
for 10 seconds)
 Normal: Both arms move
equally or not at all
 Abnormal: One arm drifts
compared to the other,
or does not move at all
Assess
 Abnormal speech
(Have the Pt. say)
“you can’t teach an old dog new
tricks”
 Normal: Patient uses correct
words with no slurring
 Abnormal: Slurred or
inappropriate words, or mute
 Stroke Warning Signs
• Kelemahan atau mati rasa/perasaan kebas pada
wajah, lengan atau tungkai, terutama pada salah satu
sisi tubuh
• Timbul gelisah, bicara tidak jelas dan tak dapat
dipahami
• Permasalahan pada penglihatan satu atau kedua mata
• Kesulitan berjalan, vertigo, kehilangan
keseimbangan dan koordinasi
• Sakit kepala berat yang muncul tanpa sebab yang
jelas (hemorrhagic stroke)
 Stroke Diagnostic Tests
• Brain imaging: CT, MR
• Cardiac Imaging: TTE, TEE, heart monitoring
• Lipid, coagulation testing
• Vascular Imaging:
Noninvasive
 MR angiography (MRA)
Intracranial, extracranial
 CT angiography (CTA)
Intracranial, extracranial
 Ultrasound: Carotid, TCD
Invasive
 Conventional cerebral angiography
Image courtesy of Regional Neurosciences Unit,
Newcastle General Hospital, Newcastle, UK.
 Diagnosis: CT Scan
– Distinguishes reliably between haemorrhagic and
ischemic stroke
– Detects signs of ischemia as early as 2 h after
stroke onset
– Identifies haemorrhage immediately
– Detects acute SAH in 95% of cases
– Helps to identify other neurological diseases (e.g.
neoplasms)
CT: Cerebral infarction

Brain swelling

Focal cortical effacement

Ventricular compression
 STROKE EMERGENCY BRAIN IMAGING:
NONCONTRAST CT SCAN
Acute (4 hours) Subacute (4 days)
Infarction Infarction
R L R L

Subtle blurring of gray-white Obvious dark changes &

junction & sulcal effacement “mass effect” (e.g.,
ventricle compression)
 STROKE EMERGENCY BRAIN IMAGING:
NONCONTRAST CT SCAN
Intracerebral Hemorrhage Subarachnoid Hemorrhage

CT detects all ICHs CT detects 90% of SAHs;

immediately if SAH suspected &
CT negative, must LP
 Management of Cerebrovascular Disease:
Current Strategies
• Treatment of risk factors in large populations
• Treatment of highest risk persons
• Management of acute stroke
• Prevention and treatment of medical and neurological
complications
• Rehabilitation
• Prevention of recurrent stroke
 Stroke Therapy: Overview

• Risk Factors:
– Lifestyle modification
– Risk factor management
• Acute stroke therapy
• Prevention of stroke:
– Primary prevention
– Secondary prevention
 Strategies for Preventing Stroke and
Reducing Stroke Disability

stroke
blood pressure mortality
glucose
smoking mass popl.
lipids strategy acute treatment

First stroke Secondary recurrent

prevention stroke
high risk strategy
Rehabilitation
hypertension
TIA
Atrial fibrillation
other vascular disease Stroke related
disability
 Management: Improved CBF

Cerebral arterial Decreased CBF Brain tissue

Cerebral autoregulation
stenosis/occlusion (endothelial function etc) ischemia
LAA/CE/SVD/others

• Prevention: endarterectomy, stenting

• Acute management: thrombolytics – medical and mechanical
• Targeting endothelial cell functions (ACEI, calcium blocker,
statins, etc.)
 Antithrombotic Therapies to Prevent
Ischemic Stroke
• Oral anticoagulants
• Antiplatelet agents
– Aspirin 50-325 mg/day
– Ticlopidine 250 mg twice daily
– Clopidogrel 75 mg/day
– Aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice a
day
 Time Target

• Door to doctor 10 min

• Access to neurologic expertise 15 min
• Door to CT scan completion 25 min
• Door to CT scan interpretation 45 min
• Door to treatment 60 min
 AIS ED STROKE CARE 24/7:
1-H EVALUATION, 1-H INFUSION

I. Triage–10 min III. CT & Labs–45 min

– Review t-PA criteria – Obtain lab results
– Page acute stroke team – Read CT
– Draw pre t-PA labs* – Return pt to ED
II. Medical Care–25 min IV. Treatment–60 min
– Place O2 , 2 NS IVs
– Start IV t-PA
– Obtain BP, weight,
– Monitor for ICH sxs
NIHSS
• HTN, headache
– Obtain 12-lead ECG
– Send patient to CT • N/V,  neuro
status
*CBC, platelets, PT/INR, PTT, chem 7, cardiac panel
 What is the Penumbra device?
• The Penumbra is a
recently approved device
(2008) that can be used to
“vacuum” out the cerebral
blood clot
– A tiny vacuum cleaner for the
brain

• Can be tried up to 8 hours

after a stroke strikes or after
failure of thrombolytic
therapy
– FDA approved 12/08
 Management of Risk Factors

• Non-pharmacological intervention:
– Life style modification: cessation of smoking,
drinking
– Exercise, weight reduction
• Pharmacological intervention:
– DM, HTN, hyperlipidemia, cardiac diseases,
 Perceptions of Stroke
Reality :
Myth – Stroke: Up to 80 percent of strokes
Is not preventable are preventable
Stroke requires emergency
Cannot be treated treatment
Only strikes the elderly Anyone can have a stroke
Happens in the heart Stroke is a “Brain Attack”
Recovery ends after 6 Stroke recovery can last a
months lifetime
© 2011 National Stroke Association
TERIMA KASIH