Stroke
Chih-Ping Chung, MD PHD
Department of Neurology, Taipei Veterans General Hospital
National Yang Ming University
腦中風 : 定義
• 腦中風 :
快速發展之腦部功能局部或全面障礙, 症狀持
續 24 小時以上,或造成死亡. 除了血管病變外,
無其他明顯原因.
• 種類:
– 阻塞性 (ischemic stroke)
– 出血性 (hemorrhagic stroke)
CI: cerebral infarction
ICH: intracerebral hemorrhage
Ischemic Stroke
• Cerebral vessel anatomy and collaterals
• Ischemic stroke classification (etiology-based)
• Cerebral microvessel
• Brain tissue ischemia
• Management: increased cerebral blood flow
(CBF)
Major Arteries supplying Brain:
Anterior Circulation vs. Posterior Circulation
Anterior Circulation
Collateral circulation
Circle of Willis
Extracranial arterial collateral
circulation
• facial (a), maxillary (b),
and middle meningeal
(c) arteries to the
ophthalmic artery
• dural arteriolar
anastomoses from the
middle meningeal
artery (d) and occipital
artery through the
mastoid foramen (e)
and parietal foramen (f)
Intracranial arterial collateral
circulation
• leptomeningeal anastomoses between anterior
and middle cerebral arteries (b) and between
posterior and middle cerebral arteries (c)
Ischemic Stroke
• Cerebral vessel anatomy and collaterals
• Ischemic stroke classification (etiology-based)
• Cerebral microvessel
• Brain tissue ischemia
• Management: increased cerebral blood flow
(CBF)
Etiologies of ischemic stroke
• Large artery atherothromboembolism
• Cardioembolism
• Small vessel occlusion (Lacunar infarction)
• Others
Atherosclerosis
Etiologies of ischemic stroke
• Large artery atherothromboembolism
• Cardioembolism
• Small vessel occlusion (Lacunar infarction)
• Others
High risk source of cardiogenic emboli
History Cardiovascular evaluation
• Mechanical prosthetic heart • Echo: dilated
valve cardiomyopathy, atrial
• Af myxoma, infective
• Sick sinus syndrome endocarditis, akinetic left
ventricular segment, left
• MI within 4 weeks atrial thrombus, left
• Dilated cardiomyopathy ventricular thrombus
• Atrial myxoma • ECG: Af demonstrated at
• Infective endocarditis any time during
• Akinetic left ventricular hospitalization, AMI
segment • Holter monitor: Af
• Left ventricular thrombus demonstrated at any time
during hospitalization, sick
sinus syndrome
Etiologies of ischemic stroke
• Large artery atherothromboembolism
• Cardioembolism
• Small vessel occlusion (Lacunar infarction)
• Others
Small vessel disease
• 1965, CM Fisher – clinico-
pathological studies of
lacune (Fisher 1969, 1977,
1978, 1979, Fisher and
Caplan 1971, Fisher and
Tapia 1987)
• He coined the term “lacune”:
specific pathological and
radiological presentations
Small vessel disease
• Subcortical small
infarction
• Long penetrating
arterioles: from the pial
network located on the
surface of the brain
Perforating arteries
Perforating arteries
Small vessel disease: lacune
Fisher’s theory: from the observations of
parenchyma and vessel pathology
Lipohyalinosis & microatheroma
Microemboli
Ischemic Stroke
• Cerebral vessel anatomy and collaterals
• Ischemic stroke classification (etiology-based)
• Cerebral microvessel
• Brain tissue ischemia
• Management: increased cerebral blood flow
(CBF)
Microvessels
• Arteriole: An arteriole is a small diameter blood vessel that
extends and branches out from an artery and leads to capillary.
Blood-brain barrier
Thin muscular walls (usually only one to two layers of smooth
muscle) and are the primary site of vascular resistance.
• Capillary: 5 – 10 um; composed of only a single layer of cell, the
endothelium.
• Venule: A little vein. Venules go from capillaries to veins. Thin
muscular walls
Capillary
• Enable the interchange of water, oxygen, carbon dioxide, and
many other nutrient and waste chemical substances between
blood and surrounding tissues.
• Perfusion pressure: the net pressure gradient causing blood
flow to the brain. It must be maintained within narrow limits
because too little pressure could cause brain tissue to become
ischemic (having inadequate blood flow), and too much could
raise intracranial pressure (ICP) or/and BBB damage and
vasogenic edema.
• CPP = MAP − ICP (if ICP is higher than JVP)
Or
CPP = MAP − JVP (if JVP is higher than ICP).
• Cerebral blood flow (CBF) is driven by cerebral perfusion
pressure (CPP)
Microangiopathy
• Ischemia (perfusion pressure)
• Increased vascular permeability: BBB
damage – vasogenic edema –
IICP/hemorrhage
Arteriole:
Cerebral autoregulation
• CBF is regulated by a complex system influenced by multiple
factors: CPP, brain metabolic activity, autonomic innervation,
vasodilators (CO2, NO), and drugs (acetazolamide)
• CA: The CBF is kept relatively constant within a wide range of
the CPP.
• Endothelium and smooth muscle
CPP = ABP – ICP (JVP)
Cerebral autoregulation is maintained by
different hypothesized control pathways
• Vasogenic
• Metabolic
Vasogenic mechanism
Intrinsic ability of cerebral vessels to responses to changes in transmural
pressure.
Stroke 2003;34:1645-1649 Stroke
1994;25:793-797 Stroke
1995;26:1014-1019
Vasogenic mechanism
Animal study
• Intraluminal pressure:
controlled by smooth muscle,
modulated by endothelium
(intracellular signals – Ca2+
influx)
• Flow: controlled by
endothelium, mediated by
NO
These counteracting mechanisms assure optimal adjustment of the
vessel diameter to CPP at any time.
Circ Res 1995;77:832-840 Nuclear Medicine Review 2007;10:29-42 Circ Res
1990;66:1445-1448 Stroke 1998;29:1194-1200
Metabolic regulation
• Arteriolar resistance is
modified by waste products
of energy metabolism (CO2),
partial pressure of O2, and
release of specific
vasoactive substances such
as adenosine and potassium
ions from neurons in
response to insufficient
blood supply.
Stroke 1977;8:358-360 Stroke
2002;33:844-849
Cerebral microvascular pathology
HTN
Aging
• Hyaline
arteriosclerosis
• Lipohyalinosis
• Atherosclerosis
Cerebral hypoperfusion (acute ischemia
Obstruction
and chronic ischemia) in aging/HTN
Impaired autoregulation function subjects
BBB damage Vasogenic edema, microbleeding
Cerebral small vessel disease
1. Lacunar infarction
Cerebral small vessel disease
2. Leukoaraiosis (age-related white matter changes)
Leukoaraiosis
• Risk factors:
aging and HTN
• Chronic cerebral
hypoperfusion
(decreased CBF
globally)
• BBB
Vessel pathology in LA: fibrosis
• Hyaline arteriosclerosis: Degeneration of the media
associated with depositions of collagens type I, III, IV, V, as
well as other components of extracellular matrix in media and
adventitia; increased amounts of basal lamina components
• Pericapillary sclerosis: the proliferation of collagen fibrils in
the media and adventitia of the blood vessels is not specific to
small arteries and arterioles but also occurred in the
pericapillary spaces
• Capillary and arteriolar loss
• Venous collagenosis
Ischemic Stroke
• Cerebral vessel anatomy and collaterals
• Ischemic stroke classification (etiology-based)
• Cerebral microvessel
• Brain tissue ischemia
• Management: increased cerebral blood flow
(CBF)
Brain tissue ischemia
Ischemic Stroke
• Cerebral vessel anatomy and collaterals
• Ischemic stroke classification (etiology-based)
• Cerebral microvessel
• Brain tissue ischemia
• Management: increased cerebral blood flow
(CBF)
Management
Cerebral arterial Decreased CBF Brain tissue
stenosis/occlusion Cerebral autoregulation
ischemia
LAA/CE/SVD/others (endothelial function etc)
• Improved CBF
• Neuroprotection
Neuroprotection
Management: improved CBF
Cerebral arterial Decreased CBF Brain tissue
stenosis/occlusion Cerebral autoregulation
ischemia
LAA/CE/SVD/others (endothelial function etc)
• Prevention: endarterectomy, stenting
• Acute management: thrombolytics – medical
and mechanical
• Targeting endothelial cell functions (ACEI,
calcium blocker, statins, etc.)
Take home messages
• Ischemic stroke is a heterogeneous disease
• Cerebral microvessel: specific structures and
functions
• How to improve CBF