Introduction

Bornstein NM (ed): Stroke. Basel, Karger, 2009, pp 1–8

Anatomy and Pathophysiology of Stroke

Eitan Auriel
Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Anatomy of Stroke

Stroke is defined as a sudden neurological deficit caused by impairment in perfu-

sion to the brain. The clinical manifestations of ischemic and hemorrhagic stroke are
direct consequences of the territory of the vessels involved. Stroke in the posterior
circulation, for instance, may result in diplopia, vertigo and dysphagia while stroke
involving the left anterior circulation may manifest itself as aphasia and right hemi-
paresis. In order to understand the clinical impact of stroke, it is highly crucial for the
treating physician to be familiar with neurovascular anatomy.
Although the average brain weighs 1.3 kg, as much as 20% of the cardiac output is
delivered to it. The brain is supplied in the anterior aspect by the two internal carotid
arteries and posteriorly by the two vertebral arteries which lie within the subarach-
noid space. The anastamoses of the four arteries create the circle of Willis [1, 2].
The neurovascular anatomy of the brain blood supply and the physiology of stroke
are summarized in this chapter.

Anterior-Carotid Circulation

The internal carotid artery begins at the bifurcation of the common carotid artery
to the external and internal carotids [1–4]. The right common carotid arises from
the brachiocephalic (innominate) artery and the left common carotid arises directly
from the aortic arch. While the external carotid supplies the face, the internal carotid
directly penetrates the base of the skull, with no other branches till there, through
the carotid canal to supply the anterior aspect of the cerebrum. The first branch
of the internal carotid artery at the level of the cavernous sinus is the ophthalmic
artery, which enters the orbit through the optic canal together with the optic nerve
and supplies the retina and choroid via its terminal branches – the central retinal
artery and the posterior ciliary arteries. Occlusion of the ophthalmic artery results
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in monocular blindness. The vision loss caused by temporal arteritis, a condition
in the elderly characterized by headache, jaw claudication, diplopia and systemic
manifestations including fever, weight loss, anemia and elevated sedimentation rate,
is the result of vasculitis involving the posterior ciliary artery. The sudden onset of
painless monocular blindness lasting several minutes with complete resolution, a
condition known as amaurosis fugax, is a consequence of a transient ischemia in
the retinal artery. The second branch of the internal carotid is the posterior com-
municating artery which is a small artery that runs posteriorly to join the posterior
cerebral artery of the posterior circulation forming a very important connection
between the anterior (carotid) and posterior (vertebro-basilar) circulation and part
of the circle of Willis. An aneurysm of this artery is the second most common aneu-
rysm in the circle of Willis and may manifest itself as third (oculomotor) nerve palsy
with involvement of the pupil (diplopia, ptosis and mydriasis) [4]. The next branch
is a small artery called the anterior choroidal artery which supplies, among others,
the optic tract and the posterior limb of the internal capsule. Occlusion of the ante-
rior choroidal may result in contralateral weakness or paralysis of the limbs due to
an infarct in the motor pathways of the internal capsule. Some patients with stroke
in the territory of the anterior choroidal artery also present with some degree of sen-
sory visual field deficits [5]. After the rising out of the anterior choroidal artery, the
internal carotid bifurcates into its two main branches, i.e. the anterior and middle
cerebral arteries which supply most of the cerebrum. The anterior cerebral artery
(ACA) is the smaller of the two and provides blood supply to the medial surface of
the hemisphere as far as up to the parieto-occipital sulcus. Since the medial aspect
of the hemispheres, due to the structure of the homunculus, contains the motor and
sensory cortex of the foot and leg, infarct in the territory of the ACA may result in
various degrees of weakness and sensory loss of the contralateral leg with no, or only
mild, involvement of the contralateral hand. An important branch of the ACA is the
medial striate artery (artery of Heubner) which supplies part of the internal capsule
and the basal ganglia. Its occlusion may cause contralateral hemiparesis. The two
ACAs, the right and the left, are connected by the anterior communicating artery
which serves as the anterior connection between the right and left carotid circula-
tions and may compensate as a collateral in the case of occlusion in one of the inter-
nal carotid arteries by ‘cross-filling’. The anterior communicating artery is the most
common site of aneurysm in the circle of Willis that may result in bleeding into the
subarachnoid space [4].
The middle cerebral artery (MCA) is the largest branch of the internal carotid
artery, it runs laterally and supplies most of the lateral surface of the hemisphere and
provides blood to the motor and sensory cortex of the face, arm and hand; therefore,
stroke in the MCA territory results in any degree of motor and sensory deficit mainly
involving the contralateral side of the face and upper extremity with lesser involve-
ment of the contralateral lower extremity. The upper division of the MCA in the dom-
inant hemisphere also supplies the Broca language area in the frontal lobe. A stroke
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 Anterior
Middle Anterior
communicating
cerebral cerebral
artery
artery artery
Ophthaimic
artery

Internal
carotid
artery Anterior
choroidal
artery
Posterior
communicating
artery
Posterior
cerebral
artery

Pontine Superior
arteries cerebral
Basilar artery
artery

Anterior
inferior
cerebellar
artery

Vetebral
artery

Posterior
Anterior infenor
Spinal cerebellar
artery artery

Fig. 1. The circle of Willis.

involving this branch may result in motor aphasia characterized with nonfluent, tele-
graphic speech and intact comprehension. The lower division of the MCA supplies
the Wernicke language area in the temporal lobe. Damage to this area results in sen-
sory aphasia characterized by nonfluent speech and poor comprehension. If both the
Broca and the Wernicke areas are damaged by ischemia due to a massive MCA stroke,
the aphasia may be global and the patient is mute [2, 4]. Another strategic area sup-
plied by the MCA is the frontal eye field (FEF) in the frontal lobe which is responsible
for the saccadic eye movements toward the contra-lateral direction. Infarct in this ter-
ritory may, therefore, cause eye deviation to the side of the lesion. In its proximal part,
also known as the M1 segment, the MCA gives rise to its penetrating arteries, the
lateral striate arteries, which supply some of the basal ganglia and internal capsule.
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Occlusion of these arteries causes contralateral hemiparesis or hemiplegia to an equal
extent in the face, hand and leg due to an infarct in the internal capsule.

Posterior Vertebro-Basilar Circulation

The brain stem, cerebellum and the posterior aspect of the cerebrum are supplied by
the two vertebral arteries [1–4]. The vertebral arteries arise from the first part of the
sub-clavian artery, ascend in the neck through the two vertebral canals in the transverse
processes of the upper six cervical vertebras, and enter the skull through the foramen
magnum. In the lower pons, the two vertebral arteries join together to form the basilar
artery. Before doing so, the vertebral arteries branch off the anterior and posterior spi-
nal arteries which supply the upper part of the spinal cord and the posterior inferior
cerebellar artery (PICA) which supply the dorsolateral aspect of the medulla and the
inferior surface of the cerebellum. Although rare, stroke involving the spinal arteries
causes the loss of motor and sensory functions below the level of the occlusion. Infarct
in the territory of the PICA results in the classic Wallenberg syndrome (lateral medul-
lary syndrome) [4] which presents with sudden onset of vertigo, vomiting, dysphagia,
dysarthria, ipsilateral hemiataxia, ipsilateral Horner syndrome (including ptosis and
miosis) and sensory loss over the ipsilateral face and contralateral limbs.
The basilar artery gives rise to the pontine arteries, anterior inferior cerebellar
artery and the superior cerebellar artery, all of which supply the upper brain stem
and cerebellum. The anterior inferior cerebellar artery also forms the labyrinth artery
which supplies the cochlea and labyrinth of the inner ear. In some cases, the labyrinth
artery is a direct branch of the basilar artery. One should consider vascular origin in
the differential diagnosis of sudden deafness.
The terminal branches of the basilar artery are the two posterior cerebral arteries
(PCA) which are connected to the anterior circulation by the posterior communicat-
ing artery forming the circle of Willis. Rarely, the PCAs or one of them arise directly
from the internal carotid artery. The PCAs supply the midbrain, thalamus, occipi-
tal lobe and part of the temporal lobe. Since the occipital lobe includes the primary
visual cortex, infarct in one of the PCAs results in contralateral visual field defect –
homonymous hemianopia [4]. Because the macula is supplied by divisions from the
MCA of the anterior circulation, the homonymous hemianopia spares the macula
(macular-sparing phenomena). Stroke involving the two PCAs, due to occlusion at
the top of the basilar artery, causes cortical blindness seldom combined with psy-
chiatric manifestations because of thalamic involvement which is also supplied by
perforants arising from the proximal parts (P1) of the PCAs. Note that patients with
cortical blindness have an intact pupillary response to light since the light reflex is not
mediated through the cortex. In some cases, the patients with cortical blindness may
not be aware of their vision loss and even deny it. This rare and interesting phenom-
ena is known as Anton’s syndrome.
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Venous Circulation

The venous drainage from the brain is mainly into the sinuses which are vascular canals
lying on the surface of the dura and draining into the internal jugular veins which leave
the skull through the jugular foramens [1–4]. There are two venous drainage systems
in the brain: the superficial system and the deep system. The superficial system cortical
veins drain mostly to the great anastamostic vein of Trolard and the small anastamos-
tic vein of Labbe. The great cerebral vein of Galen drains the deep cerebral veins into
the straight sinus where it meets the inferior sagittal sinus. The strait sinus joins the
superior sagittal sinus to form the confluence of sinuses, from there the blood drains
through the transverse sinus and the sigmoid sinus into the internal jugular veins. The
cavernous sinuses are venous spaces on either side of the sella turcica. They receive
blood from the ophthalmic veins which draine the blood from the orbit into the pet-
rosal sinuses. They contain cranial nerves 3, 4 and 6, the ophthalmic and maxillary
branches of cranial nerve 5, the post-ganglionic fibers of the oculosympathetic path-
way and the siphon of the internal carotid artery. Hypercoagulable states, pregnancy,
post-partum period, malignancy and infections involving the skull may predispose to
sinus vein thrombosis characterized by headache, papilledema and focal neurological
deficits. Thrombosis of the cavernous sinus may result in proptosis and loss of visual
acuity due to disruption of venous drainage from the orbit combined with ophthalmo-
paresis and diplopia results from compression of the cranial nerves [4].

Pathophysiology of Cerebral Ischemia and Infarct

It has been estimated that the brain accounts for about 18–20% of blood and oxygen
consumption of the body. Cerebral blood flow (CBF) is a result of several variables
including mean arterial pressure, resistance to the flow which depends on the size
of cerebral arteries, and blood viscosity [6]. CBF remains constant despite alterna-
tions in systemic blood pressure due to the ability of the cerebral arteries to respond
by vasodilatation to decreased blood pressure and by vasoconstriction to elevated
blood pressure. This capacity of the cerebral blood vessels to react is called autoregu-
lation [6]. Cerebral autoregulation involves several complex mechanisms adapting
blood flow to fluctuations of systemic blood pressure and is impaired after stroke so
that CBF depends mainly on systemic blood pressure. Metabolic mechanisms such
as alternations in pH and CO2 and neural control mediated by the sympathetic and
parasympathetic pathways regulate regional CBF and maintain autoregulation.
Many factors may influence CBF. Hypothermia, for instance, is associated with
decrease CBF while hyperthermia causes an increased CBF. Elevation in PCO2 results
in vasodilatation and markedly elevated CBF and vice versa [7]. In order to maintain
CBF in the setup of increased intracranial pressure (ICP), there is a compensatory
increase in the arterial blood pressure up to a limit.
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 90

Cerebral blood flow

(ml/min/100g)
50

20
20 60 100 140 160
Fig. 2. Cerebral autoregula- Mean arterial pressure (mmHg)
tion.

The normal CBF is 55 ml/100 g brain tissue/min [1, 4]. In vascular ischemia there
is secondary lack of oxygen and glucose which causes changes in intracellular metab-
olism and finally neuronal death. The critical level of cerebral ischemia is set at 23
ml/100 g/min. In the case of rapid reperfusion up to normal values, the functional
damage is reversible. When the CBF drops below 12 ml/100 g/min, an infarction is
caused and the structural and functional damage incurring is irreversible. EEG in this
case is found to be isoelectric. The peri-infarct tissue in which there is still reversible
functional impairment with CBF ranges between 12 and 23 ml/100 g/min is called
the ischemic penumbra. In order to compensate the impaired perfusion, the ischemic
brain reduces its metabolic demands and decreases the level of energy-producing
substances [6]. EEG in this territory demonstrates decreased amplitude and flatten-
ing but is not isoelectric as in the infarcted tissue. In animal models of focal cerebral
ischemia, infarct size correlates with the number of peri-infarct-spread depressions
like depolarizations [8, 9]. These depolarizations are generated in the border zone
of the ischemic lesion and spread into the peri-infarct tissue. Rapid reperfusion to
this region may salvage this tissue. This rationale stands on the basis of thrombolytic
therapy in the phase of acute stroke. The metabolic changes in the ischemic penum-
bra include increased extracellular K levels and depletion in ATP, but these biochemi-
cal changes are still reversible if reperfusion occurs. If the ischemia persists there is
marked ATP depletion, suspension in protein synthesis, increased intracellular Ca
levels, decreased pH (acidosis), accumulation of free radicals and lactic acid, cell swal-
lowing due to increased intracellular water content, and eventually neuronal death [4,
10]. This cascade of events is mediated by several neurotransmitters especially gluta-
mate. These subjects will discussed in detail in the chapter on the mechanism of brain
ischemia.
The mechanisms of ischemic neuronal death have not been fully defined and the
relative contribution of apoptotic ‘programmed cell death’ and necrotic processes
remains controversial. Necrotic cell death is characterized by cell swelling, membrane
disruption, and random DNA breaks, whereas apoptotic death involves DNA frag-
mentation and the appearance of apoptotic bodies [11].
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 Diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI,
PWI) are imaging modalities which are able to detect the ischemic lesion within min-
utes after the onset of circulatory impairment and have found wide application in the
study and management of acute stroke. These functional imaging techniques have
the advantage of giving a quantitative estimate of CBF as well as information on how
metabolic changes develop in the ischemic tissue [12, 13].
The many attempts to inhibit this cascade in vivo in human acute brain ischemia
with neuroprotective drugs such as anti-glutamenergic agents and free radical scav-
engers have failed to date, although glutamate antagonists inhibit peri-infarct-spread
depressions and reduce infarct size in animal models [14]. This may be due to the
complexity and involvement of many processes in the ischemic cascade, inappropri-
ate time window in which the drugs were administrated, and the fact that only less
then 5% of the brain tissue is consists of neurons, while the other 95% consists of glia
cells which are also damaged by the ischemia. Other explanations for the failure of
neuroprotection in human studies may include insufficient drug dose and slow drug
availability at the target area, too small sample sizes in trials, and imbalance of impor-
tant baseline variables [15].
Several studies recently emphasized the role of inflammation in the acute phase
and the correlation between inflammation and early and late clinical outcomes, early
clinical worsening, and extent of brain damage. Variables which were found to be
predictors of worse stroke outcome include erythrocyte sedimentation rate, levels of
C-reactive protein, interleukin-6, tumor necrosis factor-α and intercellular adhesion
molecule-1. Current data indicate that inflammation participates in the pathophysi-
ology of arteriosclerosis and can act as the link between arteriosclerosis and athero-
thrombosis [16].
Edematous complications of stroke in the brain consist of cytogenic and vasogenic
edemas. Cytogenic edema occurs immediately after the acute ischemic attack due
to interruption to the NA/K pump and increased intracellular osmolarity and water
content, and at a later phase, vasogenic edema appears due to disruption of the blood-
brain barrier. Vasogenic edema is characterized by brain swallowing which is visible
on neuroimaging and may end with herniation of the brain, a severe and life-threat-
ening complication occurring in the first days after stroke onset [4, 17].

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Eitan Auriel, MD
Department of Neurology
Tel Aviv Sourasky Medical Center
6 Weitzman St
IL- 64239 Tel Aviv (Israel)
Tel. +972 3 6973424, Fax + 972 3 6973158, E-Mail eitanman1@gmail.com
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