Stroke and

Cerebrovascular
Diseases

Regin Filamel Escalada, MD, FPNA

Cerebrovascular Diseases
Ischemic stroke Hemorrhagic stroke
Three main processes: • ICH: chronic hypertension, coagulopathies
that arise endogenously or as a result of
• (i) atherosclerosis with superimposed anticoagulant medications, vascular
thrombosis affecting large cerebral or malformations of the brain, cranial trauma,
extracerebral blood vessels and hemorrhage that occurs within the
area of an ischemic stroke
• (ii) cerebral embolism
• SAH: rupture of a developmental
• (iii) occlusion of small cerebral vessels
aneurysm arising from the vessels of the
within the parenchyma of the brain circle of Willis, cerebral trauma and
arteriovenous malformations, and rarer
processes.
CLINICAL STROKE SYNDROME
• in all forms of stroke the essential feature is
abruptness with which the neurologic deficit develops
– Embolic strokes: occur suddenly and the deficit reaches its
peak almost at once
– Thrombotic strokes: tend to evolve somewhat more slowly
over a period of minutes or hours and occasionally days; in the
latter case, the stroke usually progresses in a saltatory fashion,
i.e., in a series of steps rather than smoothly
– ICH: also abrupt in onset, the deficit may be virtually static or
steadily progressive over a period of minutes or hours
– SAH: almost instantaneous
• second essential feature of stroke is its focal signature
and the size of the infarct or hemorrhage
– Hemiplegia: most typical sign of cerebrovascular diseases,
whether in the cerebral hemisphere or brainstem
Differentiation of Stroke from Other
Neurologic Illnesses
• The three criteria by which the stroke is identified should be reemphasized:
• (1) the temporal profile of the clinical syndrome
• (2) evidence of focal brain disease
• (3) the clinical setting
Epidemiology of Cerebrovascular
Diseases
• third most common cause of death in the United States
• 700,000 cases/ year (600,000 ischemic lesions and 100,000 hemorrhages,
intracerebral or subarachnoid)
• 175,000 fatalities
• 7.8 million deaths yearly throughout the world and represents about 13
percent of all causes of death
• cause significant physical, emotional, and cognitive disabilities among
survivors, accounting for 3.6 percent of the total disability-adjusted life years
(DALYs) and thus placing stroke within the 10 leading causes of disability
Risk Factors for Stroke
• The most important of these are hypertension, atrial fibrillation, diabetes
mellitus, cigarette smoking, and hyperlipidemia.
• Hypertension the most readily recognized factor in the genesis of primary
intracerebral hemorrhage.
• As for embolic strokes, the most important risk factors are structural cardiac
disease and arrhythmias, mostly atrial fibrillation and rheumatic valvular
disease; increase incidence 6x in AF, 18x in RVD
• Diabetic patients to be 2x as liable to stroke as age-matched nondiabetic
groups
• The importance of long-duration cigarette smoking in the development of
carotid atherosclerosis has long been known
Risk Factors for Stroke
• As in the case of coronary artery disease, the level of low-density lipoprotein
(LDL) cholesterol has the most impact on the incidence of stroke but
elevated triglycerides may also confer risk.
• Subsidiary factors, such as low potassium intake and reduced serum levels of
potassium, are associated with an increased stroke rate in several studies,
including one in which we participated, but the mechanism of this effect is
obscure
• Genetics: polymorphism on chromosome 12, encompassing several genes
that have putative connections to vascular disease
The Major Causes of Cerebral Vascular
Occlusion and Ischemic Stroke
1 Atherothrombosis
• The evolution of clinical phenomena in cerebral thrombosis, both of large intracranial
(basilar, carotid) or extracranial (carotid, vertebral) and small vessels (lacunes), is more
variable than that of embolism and hemorrhage
• Half of patients the stroke is preceded by minor signs or one or more transient attacks of
focal neurologic dysfunctionan that of embolism and hemorrhage
• Characteristic is a "stuttering" or intermittent progression of neurologic deficits extending
over several hours or a day or longer
• Several parts of the body may be affected at once or only one part, such as a limb or one side
of the face, the other parts becoming involved serially in step-like fashion until the stroke is
fully developed.
• Also characteristic occurrence during sleep; the patient awakens paralyzed, either during the
night or in the morning
• Atheromatous plaques preferentially form at branching points and curves of
the cerebral arteries. The most frequent sites are:
1. internal carotid artery, at its origin from the common carotid
2. cervical part of the vertebral arteries and at their junction to form the basilar
artery
3. stem or at the main bifurcation of the middle cerebral arteries
4. proximal posterior cerebral arteries as they wind around the midbrain
5. proximal anterior cerebral arteries as they pass anteriorly and curve over the
corpus callosum
2. Cerebral Embolism
• This is the most common cause o f ischemic strokes and of all the types of stroke,
cerebral embolism develops most rapidly, "like a bolt out of the blue“
• As a rule, the full-blown picture evolves within seconds, exemplifying most
perfectly the idealized temporal profile of a stroke
• In most cases, the embolic material consists of a fragment that has broken away
from a thrombus within the heart ("cardioembolic")
• The resultant infarction is pale, hemorrhagic, or mixed; hemorrhagic infarction
nearly always indicates embolism (although venous occlusion can do the same)
• Framingham Heart Study - chronic atrial fibrillation are approximately six times
more liable to stroke than an age-matched population with normal cardiac
rhythm (1%/year in persons younger than age 65 years, and as high as 8%/year
year in those older than age 75 years with additional risk factors)
AF
• The CHADS2 and related systems are
shorthand methods to quantitate the
risk factors that modulate risk for
stroke in a patient with atrial
fibrillation
• CHA2DS2-VASc is purported to
improve these predictions
• Mural thrombus deposited on the damaged endocardium overlying a myocardial infarct in
the left ventricle, particularly if there is an aneurysmal sac, is an important source of cerebral
emboli
• Another source of embolism is the carotid or vertebral artery, where clot forming on an
ulcerated atheromatous plaque may be detached and carried to an intracranial branch
(artery-to-artery embolism)
• Atheromatous plaques in the ascending aorta have been recognized to be a more frequent
source of embolism
• migrating or traveling embolus syndrome is most evident in cases of posterior cerebral artery
occlusion, either from a cardiogenic source or from a thrombus in the proximal vertebral
artery
• Paradoxical embolism occurs when an abnormal communication exists between the right
and left sides of the heart (particularly a patent foramen ovale [PFO] or the alternative route
of connection via a pulmonary arteriovenous fistula
• Embolic material arising in the veins of the lower extremities or pelvis or elsewhere in the
systemic venous circulation bypasses the pulmonary circulation and reaches the cerebral
vessels. Pulmonary hypertension (often from previous pulmonary embolism) favors the
occurrence of paradoxic embolism, but these strokes occur even in the absence of
pulmonary hypertension.
• Diffuse cerebral fat embolism is related to severe bone trauma. As a rule, the emboli are
minute and widely dispersed, giving rise first to pulmonary symptoms and then to
multiple dermal (anterior axillary fold and elsewhere) and cerebral petechial hemorrhages
• Cerebral air embolism is a rare complication of abortion, scuba diving, or cranial, cervical,
or thoracic operations involving large venous structures or venous catheter insertion
Transient Ischemic Attacks (TIAs)
• When brief ischemic attacks precede a stroke but disappear entirely, leaving no clinical or
imaging trace of cerebral infarction, they almost always stamp the underlying process as
atherothrombotic involving a large or small blood vessel
• involvement of virtually any cerebral artery
• present themselves as transient spells of hemiparesis, aphasia, numbness or tingling on one
side of the body, dysarthria, diplopia, ataxia, obscuration of a visual field, or combinations
thereof that replicate the stroke syndromes
• Current opinion holds that TIAs are The consensus had in the past been that their duration
should be brief, reversible episodes of focal ischemic brain disturbance without evidence of
cerebral infarction.ld be less than 24 h
• 20 % of infarcts follow TIAs occur within a month after the first attack, and approximately 50 %
within a year
• In an attempt to provide a predictive tool, various scales have been devised, among them the
"ABCD“ system devised by Rothwell and colleagues (2005) and derivatives of this scale
– Blood pressure, unilateral weakness, speech disturbance, and the duration of symptoms (all less than 1 h)
are added to produce a predictive score for stroke within 1 week
• TIAs is a predictor not only of cerebral infarction but also of myocardial
infarction
• 2/3 of all patients with TIAs are men with hypertension, reflecting the higher
incidence of atherosclerosis in this group
Transient Monocular Blindness
• transient ischemic attack of the eye, transient monocular blindness (also
called amaurosis fugax or TMB)
• visual episodes evolve swiftly over 5 to 30 s, and are described as a horizontal
shade falling (or rising) smoothly over the visual field until the eye is
completely but painlessly blind
• risk of stroke after transient monocular blindness is lower than for cerebral
TIAs from carotid atherosclerotic disease
• size of particulate material that occludes the ophthalmic and its branches'
vessels is so small that a similar event in the cerebral hemispheres would be
less likely to produce symptoms
Lacunar Transient Ischemic Attacks
• caused by occlusion of small penetrating vessels of the brain have a
propensity to be intermittent ("stuttering") at their onset and occasionally to
allow virtually complete restitution of function between discrete episodes
Mechanism of Transient Ischemic Attacks
• whether reduced blood flow or embolic particles are responsible for TIAs
• most cases intimately related to vascular stenosis and, usually, to ulceration
as a result of atherosclerosis and thrombus formation
• single transitory episode, especially if it lasts longer than 1 h, and multiple
episodes of different pattern, suggest embolism and must be distinguished
from brief (2- to 1 0-min) recurrent attacks of the same clinical pattern,
which suggest TIAs from atherosclerosis and thrombosis in a large vessel
• Ophthalmoscopic observations of the retinal vessels made during episodes of
transient monocular blindness may infrequently show either an arrest of
blood flow in the retinal arteries and breaking up of the venous columns to
form a "boxcar" pattern or scattered bits of white material temporarily blocking
the retinal arteries
Pathophysiology of Ischemic Infarction
• two pathophysiologic processes:
• 1. loss of the supply of oxygen and glucose secondary to vascular occlusion
• 2. an array of changes in cellular metabolism consequent to the collapse of
energy-producing processes, ultimately with disintegration of cell structures and
their membranes, a process subsumed under the term necrosis
• At the center of an ischemic stroke is a zone of infarction. The necrotic tissue
swells rapidly, mainly because of excessive intracellular water content
(cytotoxic edema).
• The effects of ischemia, whether functional and reversible or structural and
irreversible, depend on its degree and duration. The margins of the infarct are
hyperemic, being supplied by meningeal collaterals, and here there is only
minimal or no parenchymal damage.
• Implicit in discussions of ischemic stroke and its treatment is the existence of
a "penumbra" zone that is marginally perfused and contains at-risk but viable
neurons
• this zone exists at the margins of an infarction, which at its core has
irrevocably damaged tissue that is destined to become necrotic
• Neurons in the penumbra are considered to be physiologically "stunned" by
moderate ischemia and subject to salvage if blood flow is restored in a certain
period of time
Vascular Factors
- effects of a focal
arterial occlusion
on brain tissue
vary depending
on the location of
the occlusion and
on available
collateral and
anastomotic
channels
Phenomenon of cerebrovascular
autoregulation
• range of mean blood pressures of approximately 50 to 150 mm Hg - small pial
vessels are able to dilate and to constrict in order to maintain cerebral blood
flow (CBF) in a relatively narrow range
• accommodation eventually fails at the extremes of blood pressure, after
which CBF follows systemic pressure passively, either falling precipitously or
rising to levels that damage the walls of small vessels
Metabolic and Physiologic Factors
• critical threshold of CBF, measured by xenon clearance, below which
functional impairment occurs
• several animal species, including macaque monkeys and gerbils, the critical
level was 23 mL/ 100 g/ min (normal is 55)
– after a short period of time, CBF is restored to higher levels, the impairment of function can
be reversed. Reduction of CBF below 10 to 12 mL / 100 g/min causes infarction, almost
regardless of its duration

• critical level of hypoperfusion that abolishes function and leads to tissue

damage is therefore a CBF. between 12 and 23 mL/ 1 00 g/min
• In the region of marginal perfusion, the K level increases (as a result of
efflux from injured depolarized cells ) and adenosine triphosphate (ATP)
and creatine phosphate are depleted
• These biochemical abnormalities are reversible if the circulation is quickly
restored to normal. Disturbance of calcium ion homeostasis and
accumulation of free fatty acids interfere with full recovery of cells
• CBF of 6 to 8 mL/ 100 g/min causes marked ATP depletion, increase in
extracellular K, increase in intracellular Ca, and cellular acidosis, invariably
leading to histologic signs of necrosis.
• Free fatty acids (appearing as phospholipases) are activated and destroy the
phospholipids of neuronal membranes. Prostaglandins, leukotrienes,and
free radicals accumulate, and intracellular proteins and enzymes are
denatured.
• Cells then swell, a process called cellular, or cytotoxic edema
• cells could withstand complete absence of 02 for 20 min. After 30 min of anoxia,
there was irreversible damage, reflected by an inability of the tissue to utilize
glucose and to synthesize protein
• reduction of even 2 to 3°C (3.6 to 5.4°F) reduces the metabolic requirements of
neurons and increases their tolerance to hypoxia by 25 to 30 percent
• One area of interest has focused on the role of excitatory neurotransmitters in
stroke, particularly glutamate and aspartate, which are formed from glycolytic
intermediates of the Krebs cycle
– These neurotransmitters, released by ischemic cells, excite neurons and produce an
intracellular influx of Na and Ca
– Some current attempts at therapy, for example, are directed at limiting the extent of
infarction by blocking the glutamate receptor, particularly the NMDA (N-methyl-o-
aspartate) channel-one of several calcium channels that open under conditions of
ischemia and set in motion a cascade of cellular events eventuating in neuronal death
(apoptosis)
• It is also clear that as ATP production fails, there is significant accumulation of
lactic acid in cerebral tissue, and all the biochemical changes consequent to
the cellular acidosis occur
• The high cerebral glucose level under anaerobic conditions led to increased
glycolysis during the ischemic episode and that the accumulated lactate was
neurotoxic
Hematologic Factors
• Involved in the process of thrombosis are changes in a number of natural
anticoagulant factors such as heparin cofactor 2, antithrombin III, protein C,
and protein S
• Protein C is a vitamin K-dependent protease that, in combination with its
cofactors protein S and antithrombin III, inhibits coagulation
• deficiency of any of these factors may predispose to in situ thrombosis within
either the arterial or venous systems and is a cause of otherwise unexplained
strokes in young persons
• These hematologic factors should be sought when unexplained strokes occur
in children or young adults, in families whose members have had frequent
strokes, in pregnant or parturient women, and in women who are migraineurs
or taking birth control pills
IMAGING TECHNIQUES IN STROKE
• Magnetic resonance imaging
• -able to reveal flow voids in vessels, hemosiderin and iron pigment, and the
alterations resulting
• particularly advantageous in demonstrating small lacunar lesions deep in the
hemispheres and abnormalities in the brainstem (a region obscured by
adjacent bone in CT) from ischemic necrosis and gliosis
• main advance has been the introduction of diffusion-weighted magnetic
resonance techniques, which allow the detection of an infarctive lesion within
minutes of the stroke, i.e., considerablyearlier than CT and other MRI
sequences
• Arteriography
• enhanced by digital processing of images, accurately demonstrates stenoses and
occlusions of the intracranial and extracranial vessels as well as aneurysms,
vascular malformations, and other blood vessel diseases such as arteritis and
vasospasm
• magnetic resonance angiography (MRA), venography, (MRV), and CT
angiography
• MRA depicts the "time of flight" of blood through vessels and is not as accurate as
CT angiography in measuring the degree and morphology of changes within a
cerebral or intracranial vessel
• Vascular imaging by MRI has the advantage that areas of restricted diffusion can
be detected during the same imaging session, while the CT technique, in addition
to better resolution of vascular lumens, is preferable in circumstances requiring
the demonstration of soft tissues and bone adjacent to blood vessels, thereby
providing the surgeon with important anatomic information
• Doppler ultrasound flow studies - demonstrate atheromatous plaques and
stenosis of large vessels, particularly of the carotid but also of the
vertebrobasilar arteries
• transcranial Doppler technique - degree of precision whereby occlusion or
spasm of the main vessels of the circle of Willis can be detected and roughly
quantitated
Neurovascular Examination and Carotid
Artery Bruit
• With severe atherosclerotic stenosis at the level of the carotid sinus
auscultation discloses a bruit, best heard with the bell of the stethoscope
held against the skin just tightly enough to create a seal (excessive pressure
creates a diaphragm of the skin and filters the low-pitched frequencies that
are typical of the bruit of carotid stenosis).
• loudest at the angle of the jaw - stenosis usually lies at the proximal internal
carotid
• lower in the neck - it is in the common carotid o subclavian artery and may be
radiated from the aortic valve
THE STROKE
SYNDROMES
The distinction between vascular occlusion from a local atherosclerotic plaque with
superimposed thrombosis and an embolic occlusion is made largely on the basis of
factors already enumerated:
(1) the temporal profile of the stroke syndrome, an immediate stroke favoring
embolus, and a slowly evolving or "stuttering“ onset or emergence form sleep
with a stroke favoring atherosclerosis
(2) associated medical risk factors such as atrial fibrillation (strongly favoring
embolus) or diabetes, hypertension, hyperlipidemia and smoking, together
favoring atherosclerosis of the small penetrating, or large trunk vessels.
Carotid Artery Syndromes
• carotid system consists of three major arteries: the common carotid, internal carotid, and
external carotid
• right common carotid artery arises at the level of the sternoclavicular notch from the
innominate (brachiocephalic) artery, left common carotid comes directly from the aortic
arch
• Common carotid arteries ascend in the neck to the C4 level, just below the angle of the
jaw, where each divides into external and internal branches (sometimes the bifurcation is
slightly above or below this point).
• Common carotid can be occluded by an atheromatous plaque at its origin in the thorax,
more often on the left side, <1%
• Occlusion of the distal intracranial
portion of the internal carotid artery
(the "T")-for example by an embolus to
its distal part-produces a clinical
picture like that of middle cerebral
artery occlusion:
• contralateral hemiplegia,
• hemihypesthesia, and
• aphasia (with involvement of the
dominant hemisphere).
• Headache
• located as a rule above the eyebrow,
on the side of the infarction, may
occur with thrombosis nor embolism
of the carotid artery, but cranial pain is
not invariable and is usually mild
• with occlusion of the middle cerebral
artery- tends to be more lateral, at the
temple
• posterior cerebral occlusion - located
in or behind the eye
• When the circulation of one carotid artery has been
incompletely compromised, reducing blood flow in both the
middle and anterior cerebral territories on that side, the zone
of maximal ischemia lies between the two vascular territories
("cortical watershed") or, alternatively, in the deep portions of
the hemisphere between the territories of the lenticulostriate
branches and the penetrating vessels from the convexity
("internal" or "deep watershed")
• The infarction in the first instance occupies a region in the high parietal
and frontal cortex and the adjacent subcortical white matter.
• Its size depends upon the adequacy of collateral vessels. Weakness tends
to involve the shoulder and hip more than the hand and face.
• With long-standing carotid stenosis, the cortical watershed zone shifts
downward toward the perisylvian portions of the middle cerebral artery
territory, even to the extent that a stroke may weaken facial movement
or cause a nonfluent aphasia.
• With impaired perfusion of the deep watershed, infarctions of varying
size are situated in the sub frontal and subparietal portions of the
centrum semiovale.
• Signs of carotid occlusion:
• transient monocular blindness or visual loss or dimness of vision with
exercise, after exposure to bright light, or on assuming an upright
position
• retinal atrophy and pigmentation
• atrophy of the iris
• peripapillary arteriovenous anastomoses in the retinae
• claudication of jaw muscles
• cardinal clinical signs of stenoses, ulcerations, and dissections of the
internal carotid artery - TIAs
 Middle Cerebral Artery Stroke
Syndromes
• middle cerebral artery (MCA) has superficial and deep
hemispheral branches that together supply the largest
portion of the cerebral hemisphere
• Cortical branches - supplies the lateral (convexity)
part of the cerebral hemisphere
• (1) the cortex and white matter of the lateral and
inferior parts of the frontal lobe-including motor areas 4
and 6, contraversive centers for lateral gaze and the
motor speech area of Broca (dominant hemisphere)
• (2) the cortex and white matter of the parietal lobe,
including the primary and secondary sensory cortices
and the angular and supramarginal gyri
• (3) the superior parts of the temporal lobe and insula,
including the receptive language area of Wernicke
 Middle Cerebral Artery Stroke
Syndromes
• Deep penetrating or lenticulostriate branches of
the MCA:
– Putamen
– large part of the head and body of the caudate
nucleus (shared with the Heubner artery)
– outer globus pallidus
– posterior limb of the internal capsule
– corona radiata
MCA Stem ( M 1 ) Occlusion Syndrome
• M1 - longitudinal portion, or the stem, that is proximal to its bifurcation
• occlusion at this site blocks the flow in the small deep penetrating vessels as
well as in superficial cortical branches
• occlusion at the distal end of the stem blocks only the orifices of the divisions
of the artery in the sylvian sulcus but leaves unaffected the deep penetrating
vessels
• picture of total occlusion of the stem:
– contralateral hemiplegia (involving the face, arm, and leg as a result of infarction of
the posterior limb of the internal capsule)
– Hemianesthesia
– homonymous hemianopia (because of infarction of LGB) with deviation of the head
and eyes toward the side of the lesion
– variable but usually global aphasia with left hemispheric lesions and anosognosia
and amorphosynthesis with right-sided lesions
Striatocapsular Infarction
• syndromes occur with deep lesions in the territory of the
penetrating, lenticulostriate vessels of the MCA
• most common type - large striatocapsular infarction, all
of their patients had a degree of hemiparesis and one-
fifth had aphasia (limited form of the Broca type) or
hemineglect
• Homonymous hemianopia
• Bilateral cerebral infarctions involving mainly the insular-
perisylvian (anterior opercular) regions manifest
themselves by a diplegia of the face, tongue, and
masseters that results in anarthria without aphasia
 MCA Branch Syndromes
Superior Division Inferior Division
• Supplying the rolandic and prerolandic areas • Supplying the lateral temporal and inferior
parietal lobes
• dense sensorimotor deficit in the
contralateral face, arm, but, to a lesser • usual result in left-sided lesions is a
extent the leg, as well as ipsilateral deviation Wernicke's aphasia
of the head a
• there is usually a superior quadrantanopia
• left-sided lesions there is initially a global or homonymous hemianopia and, with
aphasia, which changes to a predominantly right-sided ones, a left visual neglect and
nonfluent (Broca's) aphasia, with the other signs of amorphosynthesis
emergence of an effortful, hesitant,
grammatically simplified, and dysmelodic
speech
 Anterior Cerebral Artery Stroke
Syndromes
• supplies the anterior three-quarters of the medial surface of the frontal lobe,
including its medial-orbital surface, the frontal pole, a strip of the lateral
surface of the cerebral hemisphere along its superior border, and the anterior
four-fifths of the corpus callosum
• Deep branches, arising near the circle of Willis (proximal and distal to the
anterior communicating artery) supply the anterior limb of the internal
capsule, the inferior part of the head of the caudate nucleus, and the anterior
part of the globus pallidus
• largest of these deep branches is the artery of Heubner ("recurrent artery of
Heubner")
• occlusion of one anterior cerebral artery distal to the anterior communicating
artery (A2 segment) results in a sensorimotor deficit of the opposite foot and
leg and, to a lesser degree, of the shoulder and arm, with sparing of the hand
and face
• left-sided occlusion, there may be a "sympathetic apraxia" of the left arm and
leg or involuntary misdirected movements of the left arm (alien arm or hand)
• cases in which occlusions of the proximal artery (ACA), which included the
Heubner artery; resulted in right hemiplegia (predominant in the leg) with
grasping and groping responses of the right hand and buccofacial apraxia that
were accompanied by a diminution or absence of spontaneous speech,
agraphia, and a limited ability to name objects and compose word lists but
with a striking preservation of the ability to repeat spoken and written
sentences
 Anterior Choroidal Artery Stroke
Syndrome
• long, narrow artery that springs from the internal carotid, just above the
origin of the posterior communicating artery
• supplies the internal segment of the globus pallid us and posterior limb of the
internal capsule and several contiguous structures including (in most patients)
the optic tract
• penetratesthe temporal horn of the lateral ventricle, where it supplies the
choroid plexus and anastomoses with the posterior choroidal artery
 Posterior Cerebral Artery Stroke
Syndromes
• 70% - formed by the bifurcation of the basilar artery and thin posterior
communicating arteries join this system to the internal carotid arteries
• Most are embolic
• Interpeduncular branches - which arise just above the basilar bifurcation,
supply the red nuclei, the substantia nigra bilaterally, medial parts of the
cerebral peduncles, oculomotor and trochlear nuclei and nerves, reticular
substance of the upper brainstem, decussation of the superior cerebellar
peduncles, medial longitudinal fasciculi, and medial lemnisci
• P1 portion of the posterior cerebral artery, giving rise to the interpeduncular
branches (that portion between the bifurcation of the basilar artery and the
ostium of the posterior communicating artery), is also referred to as the
mesencephalic artery or the basilar communicating artery
 Posterior Cerebral Artery Stroke
Syndromes
• thalamoperforate branches (also called paramedian thalamic arteries) - arise slightly more
distally from the stem, nearer the junction of the posterior cerebral and posterior
communicating arteries (P2 segment of the artery) and supply the inferior, medial, and
anterior parts of the thalamus
• thalamogeniculate branches arise still more distally, opposite the lateral geniculate body, and
supply the geniculate body and the central and posterior parts of the thalamus
• terminal or cortical branches of the posterior cerebral artery supply the inferomedial part of
the temporal lobe and the medial occipital lobe, including the lingula, cuneus, precuneus, and
visual Brodmann areas 1 7, 18, and 19
• Occlusion of the posterior cerebral artery produces a greater variety of clinical effects than
occlusion of any other artery because both the upper brainstem, which is replete with
important structures, and the inferomedial parts of the temporal and occipital lobes lie within
its supply
The posterior cerebral and basilar arteries
Posterior cerebral artery syndromes:
three groups
• (1) proximal (involving interpeduncular, thalamic perforant, and
thalamogeniculate branches)
• (2) cortical (inferior temporal and medial occipital)
• (3) bilateral
 Proximal Syndromes
• thalamic syndrome of Dejerine and Roussy - infarction of the sensory relay
nuclei in nthe thalamus, the result of occlusion of thalamogeniculate branches
• Central midbrain and subthalamic syndromes - occlusion of the
interpeduncular branches of the posterior cerebral artery
– clinical syndromes include palsies of vertical gaze, stupor, or coma

• Syndromes of the paramedian arteries, including the proximal posterior

cerebral artery, have as their main feature a third-nerve palsy combined with
contralateral hemiplegia ( Weber syndrome), contralateral ataxic tremor
(Claude syndrome), or homolateral ataxia, hemiplegia with contralateral third-
nerve palsy (Benedikt syndrome)
• Anteromedial-inferior thalamic syndromes follow occlusion of the
thalamoperforant branches. Here the most common effect is an
extrapyramidal movement disorder (hemiballismus or hemichoreoathetosis or
less often, asterixis)
• Hemiballismus is usually a result of occlusion of a small branch to the
subthalamic nucleus (of Luys) or its connections with the pallidum.
• Occlusion of the paramedian thalamic branches to the mediodorsal nucleus
is a recognized cause of an amnesic (Korsakoff) syndrome
Cortical Syndromes of thePosterior Cerebral
Artery
• Occlusion of branches to the temporal and occipital lobes gives rise to a
homonymous hemianopia as a result of involvement of the primary visual
receptive areas (calcarine or striate cortex) or of the converging
geniculocalcarine fibers
• hemianopia may be incomplete and involve the upper quadrants of the visual
fields more than the lower ones
• Macular, or central, vision is often spared because of collateral blood supply of
the occipital pole from distal branches of the middle (or anterior) cerebral
arteries
• visual hallucinations in the blind parts of the visual fields (Cogan) or
metamorphopsia and palinopsia (Brust and Behrens)
Cortical Syndromes of thePosterior Cerebral
Artery
• Occipital infarcts of the dominant hemisphere may cause alexia without
agraphia, anomia (amnesic aphasia), a variety of visual agnosias, and rarely
some degree of impaired memory
Bilateral Posterior Cerebral Artery Stroke
Syndromes
• occur as a result of successive infarctions or from a single embolic or
thrombotic occlusion of the upper basilar artery, especially if the posterior
communicating arteries are unusually small or absent, or from global failure
of circulation
• if extensive, cause "cortical blindness" that is essentially bilateral
homonymous hemianopia, sometimes accompanied by unformed visual
hallucinations
• Sometimes the patient is unaware of being blind and denies the problem
even when it is pointed out to him (Anton syndrome)
• Bilateral mesiotemporal-occipital lesions also cause a lack of recognition of
faces (prosopagnosia)
Vertebral Artery
Stroke Syndromes
• vertebral arteries are the chief
arteries of the medulla
• each supplies the lower three-
fourths of the pyramid, the
medial lemniscus, all or nearly
all of the retroolivary (lateral
medullary) region, the
restiform body, and the
posteroinferior part of the
cerebellar hemisphere through
the posterior inferior
cerebellar arteries
Vertebral Artery Stroke Syndromes
• vertebral arteries are most often occluded by atherothrombosis in their
intracranial portion
• vertebral arteries have a long extracranial course and pass through the
transverse processes of C6 to C1 vertebrae before entering the cranial cavity,
one might expect them to be subject to trauma, spondylotic compression,
and a variety of other vertebral diseases
• Extreme extension of the neck, as experienced by women who are having
their hair washed in beauty salons, or during yoga positions, may give rise to
transient symptoms in the territory of the vertebral artery
• Dissection of the vertebral artery by contrast is well described, it declares
itself by cervicooccipital pain and deficits of brainstem function
Vertebral Artery Stroke Syndromes
• If the occlusion of the vertebral artery is so situated as to block the posterior
inferior cerebellar artery supplying the lateral medulla and inferior cerebellum
(PICA), a characteristic syndrome results with vertigo being a prominent
symptom
• If the subclavian artery is blocked proximal to the origin of the left vertebral
artery, exercise of the arm on that side may draw blood from the right
vertebral and basilar arteries, retrograde down the left vertebral and into the
distal left subclavian arterysometimes resulting in the symptoms of basilar
insufficiency, aka subclavian steal
– vertigo and other brainstem signs coupled with transient weakness on exercise of
the left arm
Vertebral Artery Stroke Syndromes
• medial medullary syndrome - occlusion of the vertebral artery or one of its
medial branches produces an infarct that involves the medullary pyramid, the
medial lemniscus, and the emergent hypoglossal fibers; the resultant
syndrome consists of a contralateral paralysis of arm and leg (with sparing of
the face), contralateral loss of position and vibration sense, and ipsilateral
paralysis and later atrophy of the tongue
 Vertebral Artery Stroke Syndromes:
Lateral Medullary Syndrome
• Aka Wallenberg syndrome
• common stroke is produced by infarction of a wedge of lateral medulla lying posterior to the
inferior olivary nucleus
• The complete syndrome comprises:
– (a) symptoms derived from the vestibular nuclei (vertigo, nystagmus, oscillopsia, vomiting)
– (b) spinothalamic tract (contralateral or, less often, ipsilateral impairment of pain and thermal sense over
half the body)
– (c) descending sympathetic tract (ipsilateral Horner syndrome-miosis, ptosis, decreased sweating)
– (d) issuing fibers of the ninth and tenth nerves (hoarseness, dysphagia, hiccough, ipsilateral paralysis of the
palate and vocal cord, diminished gag reflex)
– (e) utricular nucleus (vertical diplopia and illusion of tilting of vision and rotation of the vertical meridian,
rarely so severe as to produce upside down vision)
– (f) olivocerebellar, spinocerebellar fibers, restiform body and inferior cerebellum (ipsilateral ataxia of limbs,
falling or toppling to the ipsilateral side, and the sensation of lateropulsion)
– (g) descending tract and nucleus of the fifth nerve (pain, burning, and impaired sensation over ipsilateral half
of the face); (h) nucleus and tractus solitaries (loss of taste)
– (i) cuneate and gracile nuclei (numbness of ipsilateral limbs)
Basilar Artery Stroke Syndromes
Branches of the basilar artery may be instructively grouped as follows:
• (1) paramedian, 7 to 10 pairs, supplying a wedge of pons on either side of the
midline;
• (2) short circumferential, 5 to 7 pairs in number, supplying the lateral two-
thirds of the pons and the middle and superior cerebellar peduncles;
• (3) long circumferential, 2 on each side (the superior and anterior inferior
cerebellar arteries), which run laterally around the pons to reach the
cerebellar hemispheresand
• (4) several paramedian (interpeduncular) branches at the bifurcation of the
basilar artery and origins of the posterior cerebral arteries supplying the high
midbrain and medial subthalamic regions
Basilar Artery Stroke Syndromes
• typically because of local thrombosis that is superimposed on a preexisting atherosclerotic
plaque

• can arise in several ways:

– (1) occlusion of the basilar artery itself, usually in the lower or middle third at the site of an
atherosclerotic plaque
– (2) occlusion of both vertebral arteries, which produces the equivalent of basilar artery occlusion if the
circle of Willis is inadequate
– (3) occlusion of a single vertebral artery when it is the only one of adequate size

• When there is embolism, the clot usually lodges at the terminal bifurcation of the basilar
("top-of-the-basilar syndrome") or in one of the posterior cerebral arteries, as the clot, if
small enough to pass through the vertebral artery; easily traverses the length of the basilar
artery, which is of greater diameter than either vertebral artery
• "top of the basilar" artery occlusion is most often embolic and characterized by transient
loss of consciousness, oculomotor disturbances (roving eye movements or eyes looking
downward and inward with inability to reflexly elicit upward movements), hemianopia,
bilateral ptosis, and pupillary enlargement with preserved reaction to light
• locked-in syndrome - patient is mute and quadriplegic but conscious,
reflecting interruption of descending motor pathways in the base of the pons
but sparing of the reticular activating system
– Horizontal eye movements are obliterated but vertical ones and some ability to
elevate the eyelids are spared
– pupils become extremely small but retain some reaction to light
 Basilar Artery Branch Occlusion
• results in a remarkable number of complex syndromes that include, in various combinations,
somnolence or coma, memory defects, akinetic mutism, visual hallucinations, ptosis, disorders of
ocular movement (convergence spasm, paralysis of vertical gaze, retraction nystagmus,
pseudoabducens palsy, retraction of upper eyelids, skew deviation of the eyes), an agitated
confusional state, and visual field defects
• superior cerebellar artery - ipsilateral cerebellar ataxia of the limbs (referable to middle and superior
cerebellar peduncles); nausea and vomiting; slurred speech; and loss of pain and thermal sensation
over the opposite side of the body (spinothalamic tract)
• anterior inferior cerebellar artery (AICA) - vertigo, vomiting, nystagmus,
tinnitus, and sometimes unilateral deafness; facial weakness; ipsilateral cerebellar
ataxia (inferior or middle cerebellar peduncle); an ipsilateral Horner syndrome and
paresis of conjugate lateral gaze; and contralateral loss of pain and temperature
sense of the arm, trunk, and leg (lateral spinothalamic tract)
– most characteristic manifestation of all these basilar branch strokes is the
"crossed" cranial nerve and long tract sensory or motor deficit reflecting a
unilateral segmented infarction of the brainstem
Lacunar Stroke
• small penetrating branches of the cerebral arteries may become occluded,
and the resulting infarcts may be so small or so situated as to cause no
symptoms whatsoever
• As the softened tissue is removed by macrophages, a small cavity, or lacune,
remains
• lacunes are usually caused by occlusion of small arteries, 50 to 200 microns in
diameter, and the cribriform state, to mere thickening of vessels and fraying
of the surrounding tissue-i.e., dilated perivascular spaces (Virchow-Robin
spaces) that do not have a corresponding neurologic disease
• There appear to be three mechanisms for lacunar infarction but variants of
atherothrombosis are foremost
• 1. local type of fibrohyalinoid arteriolar sclerosis that involves the orifice or
proximal part of a small penetrating blood vessel
• 2. atherosclerosis of a large trunk vessel that occludes the origin of these same
small vessels. This is prone to involve several adjacent vessels and cause, at times,
larger lacunes or the atherosclerosis extends from a trunk vessel into a smaller one
• 3. entry of small embolic material into one of the vessels
• LOCATION (descending)
– putamen and caudate nuclei
– Thalamus
– basis pontis
– internal capsule
– deep in the central hemispheral white matter

• cavities range from 3 to 15 mm in diameter

• Fisher, in several papers, has delineated the most frequent symptomatic forms of lacunar stroke:
– 1. Pure motor hemiplegia
– 2. Pure sensory stroke
– 3. Clumsy hand-dysarthria
– 4. Ipsilateral hemiparesis-ataxia
TREATMENT OF ISCHEMIC STROKE
• major goal - reduce the incidence of stroke in the general
population by the control of modifiable risk factors ("primary
prevention")
• divided into three parts:
– management in the acute phase by measures to restore the circulation and
arrest the pathologic process
– physical therapy and rehabilitation
– measures to prevent further strokes and progression of vascular disease
Management in the Acute Phase
• Some units find it advisable to keep patients supine for the first hours or day
after an ischemic stroke, mainly to prevent hypotension and cerebral
hypoperfusion
• Several studies have confirmed the high prevalence of new or enhanced levels
of hypertension immediately following an ischemic stroke and its tendency to
decline over subsequent days even without medications
• As suggested by Britton and colleagues, it is prudent to avoid
antihypertensive drugs in the first few days unless there is active myocardial
ischemia or the blood pressure is high enough t o pose a risk t o other organs,
particularly the kidneys, or there is a special risk of cerebral hemorrhage as a
result of the use of thrombolyticdrugs
Measures to Restore the Circulation and Arrest
the Pathologic Process
• Efforts are directed at establishing a diagnosis of thrombotic stroke at the
earliest possible stage and circumventing the full deficit by all means
available without risking the safety of the patient
• If the patient is under care within 4.5 h of onset of the first symptom and this
time can be established with confidence, thrombolytic therapy with tissue
plasminogen activator (tPA) is usually indicated
Intravenous Thrombolytic Agents
• Tissue plasminogen activators (recombinant tPA) convert plasminogen to
plasmin
• effective in the treatment of coronary artery occlusion (but are associated
with a 1% risk of cerebral hemorrhage) and have a reasonably clear role in the
treatment of acute ischemic stroke
• As an alternative to the usual form of tPA, alteplase and tenecteplase are
genetically engineered mutant form of plasminogen activators
• The benchmark study organized by the National Institute of Neurological and
Communicative Disorders and Stroke (see the NINCDS and Stroke rtPA
StrokeStudy Group in the references) has provided evidence of benefit later
from intravenous tPA when patients were examined months later
• Treatment within 3 h of the onset of symptoms led to a 30 percent increase in
the number of patients who remained with little or no neurologic deficit when
reexamined 3 months after the stroke; this benefit persisted when assessed 1
year later in the study by Kwiatkowski and associates
• tPA in the NIH study was administered in a dose of 0.9 mg/kg, 10 percent of
which was given as an initial bolus, followed by an infusion of the remainder
over 1 h

• Further analysis of the NINCDS trial revealed that patients who were treated
earliest within the 3-h time frame had more benefit than those treated later;
indeed, the administration of tPA in the time period between 2.5 and 3 h after
the stroke was of less value.
Exclusion
• massive infarctions (encompassing more than two-thirds of the territory of
the middle cerebral artery)
• had high scores on a clinical stroke scale that was devised for the National
Institutes of Health study
• had uncontrolled hypertension
• more than 80 years of age
• had recently received anticoagulants (except aspirin)
• An apparently effective ancillary technique has been to supplement
intravenously administered tPA with 2 h of continuously applied transcranial
ultrasound aimed at the occluded vessel
• According to Alexandrov and colleagues, complete recanalization of the
middle cerebral artery or clinical recovery occurred within 2 h but the
outcome at 3 months did not differ from those whodid not receive ultrasound
in part because other similartrials were terminated prematurely as a result of
high rates of cerebral hemorrhage
Intraarterial Thrombolysis
• Thrombolytic substances injected intraarterially, or mechanical lysis for
disruption o r removal o f a n intravascular clot, can in some instances restore
blood flow of the middle cerebral and basilar arteries
Acute Surgical Revascularizatio n
• refers to the opening of the carotid artery or an area of intracranial
atherosclerosis immediately after a stroke with the intention of improving the
clinical outcome
Anticoagulation
• The pivotal issue in prevention of further strokes is whether the stroke or TIA
is atherothrombotic or cardioembolic.
• Heparin Treatment during an Acute Evolving Stroke
• Administration of heparin may be initiated while the nature of the illness is
being clarified; the drug is then discontinued if contraindicated by new
findings
• In the event heparin is used, and assuming tPA has not been used in the
preceding 24 h, heparin may be given intravenously, beginning with a bolus of
100 U / kg followed by a continuous drip (1,000 U /h) and adjusted according to
the partial thromboplastin time (PTT).
• use of low-molecular-weight heparin (enoxaparin or nadroparin) given
subcutaneously within the first 48 h of the onset of symptoms have uncertain
benefit
Warfarin for the Prevention of Recurrent Strokes
from Atrial Fibrillation
• most convincing evidence favoring the efficacy of anticoagulants in the
prevention of embolism comes from the Boston Area Anticoagulant Trial for
Atrial Fibrillation
• Recurrent strokes were reduced by 86 percent in the warfarin group and the
death rate was lower
• studies suggest that an INR between 2 and 3 confers better protection than
levels below 2
• Warfarin therapy, beginning with a dose of 5 to 10 mg daily, is relatively safe
provided that the international normalized ratio (INR) is brought to 2 to 3
(formerly measured as a prothrombin time between 16 and 19 s) and the level
is determined regularly (an approximate plan is once a day for the first 5 days,
then 2 or 3 times a week for 1 to 2 weeks, and finally once every several
weeks).
• Alternatives to warfarin in patients with atrial fibrillation have been explored,
such as the thrombin inhibitor ximelagatran, which has the advantage of not
requiring monitoring by blood tests (Stroke Prevention Using an Oral
Thrombin Inhibitor in Atrial Fibrillation [SPORTIF] trial)
Warfarin for the Prevention of Further Strokes in the
Weeks and Months after a First Stroke Not due to Atrial
Fibrillation
• Warfarin-Aspirin Recurrent Stroke Study (WARSS; not including
cardioembolic stroke) reported by Mohr and colleagues (2001)
– warfarin is of some value in the first 2 to 4 months following the onset of an
ischemic stroke due to atherosclerotic disease. However, the results of
controlled studies have indicated that there is no reason to favor warfarin in
comparison to aspirin in cases of atherothrombotic stroke
• introduction of factor Xa inhibitors has offered an alternative to the vitamin K
antagonist, warfarin, for reducing strokes in patients with atrial fibrillation
• Dabigatran and rivaroxaban confer similar reductions in stroke to apixaban
and warfarin
• These drugs have the advantage over warfarin of not requiring regular blood
tests for the measurement of the INR and of having fewer drug interactions
Antiplatelet Drugs
• Aspirin has proved t o b e the most consistently useful drug in the prevention
of thrombotic and possibly, embolic strokes
• One currently favored approach, based in part on the above-mentioned
WARSS trial, is to simply administer aspirin in all cases of acute stroke
• acetyl moiety of aspirin combines with the platelet membrane and inhibits
platelet cyclooxygenase, thus preventing the production of thromboxane A2,
a vasoconstricting prostaglandin, and also prostacyclin, a vasodilating
prostaglandin
• In patients who cannot tolerate aspirin, the platelet aggregate inhibitor
clopidogrel or a similar drug (such as ticlopidine or dipyridamole) can be
substituted
Other Forms of Medical Treatment
• treatment by hemodilution was popularized by the studies of Wood and
Fleischer, who showed a high incidence of short-term improvement when the
hematocrit was reduced to approximately 33 percent
• lowering blood viscosity improves regional blood flow in the heart had been
known for some time, and a similar effect on the brain has been
demonstrated by CBF studies
• Calcium channel blockers of the types administered for cardiac disease have
also been found to increase CBF and to reduce lactic acidosis in stroke
patients
Closure of Patent Foramen Ovale ( PFO )
• Even if a putative relationship between cryptogenic stroke and PFO were
established, it has been difficult to demonstrate that closing the defect
provides protection against further strokes
• closure of the PFO is recommended only as a component of a clinical trial and
the clinician is left with limited direction regarding the need for, and type of,
anticoagulation
Treatment of lnfarctive Brain Swelling and
Raised Intracranial Pressure
• In the first few days following massive cerebral infarction, brain edema of the
necrotic tissue may threaten life
• Clinical deterioration occurs usually on the third to fifth days, sometimes
later, but may rarely evolve as quickly as several hours after the onset
• Clinical indicators of worsening-drowsiness, a fixed (but not necessarily
enlarged) pupil, a Babinski sign on the side of the infarction (on the preserved
side of the body), and changes in breathing pattern, as well as characteristic
imaging signs-are all a result of secondary tissue shifts
• Intravenous mannitol in doses of 1 g/kg, then 50 g every 2 or 3 h, may
forestall further deterioration
• favored approach has been to perform hemicraniectomy fairly early in the
course of brain swelling, in the first 2 or 3 days, when the patient is drowsy
but before coma supervenes
• large advantage in survival was found favoring the group operated within 48 h
• Hydrocephalus usually develops as a prelude to deterioration and is manifest
as drowsiness and stupor, increased tone in the legs, and Babinski signs; other
sentinel signs of compression of the brainstem are gaze paresis, sixth nerve
palsy, or hemiparesis ipsilateral to the ataxia
Carotid Artery Stenosis
• Here we discuss the patient who has had TIAs or who has passed the acute
period of stroke, when surgery is considered to be safer.
• The region that most often lends itself to such therapy is the carotid sinus (the
bulbous expansion of the internal carotid artery just above its origin from the
common carotid)
• that carotid endarterectomy for symptomatic lesions causing degrees of
stenosis greater than 70 to 80 percent in diameter reduces the incidence of
ipsilateral hemispheral strokes and shows greater benefit with increasing
degrees of stenosis - North American Symptomatic Carotid Endarterectomy
Trial (NASCET) and the European Carotid Surgery Trial (ECST)
Asymptomatic Carotid Stenosis
• bruit - corresponds to the reduction in luminal diameter of the artery to 2 mm
or less and, while found in a large proportion of patients with severe stenosis
Course and Prognosis of Ischemic Stroke
• Characteristically, the paralyzed muscles are flaccid in the first days or weeks
following a stroke; the tendon reflexes are usually unchanged but may be
slightly increased or decreased. Gradually spasticity develops, and the tendon
reflexes become brisker.
• arm tends to assume a flexed adducted posture and the leg an extended one
• Many patients complain of fatigability and are depressed, possibly more so
after strokes that involve the left frontal lobe (Starkstein et al); other studies
implicate an infarct on either side of the brain
• When multiple infarcts occur over a period of months or years, special types
of dementia and gait failure may develop
• arteriosclerosis dementia and Binswanger subcortical leukoencephalopathy -
represents the accumulation of multiple white matter infarcts and lacunes
• White matter that is destroyed tends to lie in the border zones between the
penetrating cortical and basal ganglionic arteries. Large patches of
subcortical myelin loss and gliosis, in combination with small cortical and
subcortical infarcts, are evident with brain imaging
Physical Therapy and Rehabilitation
• beginning within a few days of the stroke the paralyzed limbs
ideally should be carried through a full range of passive
movement several times a day
• purpose is to avoid contracture (and capsulitis), especially at the
shoulder, elbow, hip, and ankle
• Prophylaxis for deep venous thrombosis with compression boots
or anticoagulation is appropriate if the patient cannot be
mobilized
• assessment for swallowing difficulty should be made early during
recovery and dietary adjustments on the insertion of a
nasogastric tube made if there is a risk of aspiration
• Nearly all hemiplegic patients regain the ability to walk to some
extent, usually within a 3- to 6-month period, and this should be
a primary aim in rehabilitation.
Secondary Preventive Measures
• primary objective in the treatment of a therethrombotic disease is
prevention, efforts to control the risk factors must continue after stroke. The
carotid vessels, being readily accessible, may be examined for the presence of
a bruit; the latter often indicates a stenosis
• Ultrasonography, CT, or MRA examination of the cervical and intracranial
vessels is justified in almost all patients with TIAs and ischemic stroke
Stroke from atherothrombotic disease
Preventive measures include the following
(1) aspirin, which reduces the risk of second stroke slightly, but its effect, as
already noted, is modest
(2) Administration of any required antihypertensive agents but with caution in
the first days after ischemic stroke
(3) Administration of cholesterol-lowering drugs as commented below
(4) smoking cessation
(5) during future general surgical procedures, maintenance of systemic blood
pressure and oxygenation, especially in elderly patients.
• Regarding the appropriate dose of aspirin, a consensus has been that 50 to
100 mg is adequate as a preventative measure (typically 81 mg in the United
States) and that higher doses do not offer additional benefit
• Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial -
has shown that secondary stroke prevention is possible in patients with TIA or
stroke in the prior 6 months with the use of high-dose atorvastatin (80 mg)
but the magnitude of benefit was small (approximately 3 percent).
GENERALIZED BRAIN ISCHEMIA AND
HYPOXIA
• constitutes a special type of infarction that follows cardiac arrest and other
forms of prolonged hypotension or hypoxia
• most typical configuration, seen with imaging, is of widespread cortical
infarction affecting also the deep nuclei, i.e., the most metabolically active
regions of the cerebral hemispheres
• there is a tendency for regional infarctions to occur in the areas of lowest
blood flow that lie between the major surface arteries, referred to
metaphorically as a watershed infarction
• Pure hypoxia-anoxia without hypotension produces another type of damage
in areas susceptible to reduced oxygen delivery, mainly affecting the
hippocampi; a Korsakoff syndrome results
LESS-COMMON
CAUSES OF ISCHEMIC
CEREBROVASCULAR
DISEASE
Fibromuscular Dysplasia
• segmental, nonatheromatous, noninflammatory arterial disease of unknown
etiology
• almost exclusively in women
• Uncommon, 10% familial
• internal carotid artery is involved most frequently, followed by the vertebral
and cerebral arteries
• narrowed arterial segments show degeneration of elastic tissue and irregular
arrays of fibrous and smooth muscle tissue in a mucous ground substance
Dissection of the Cervical
and Intracranial Arteries
• Internal Carotid Artery Dissection
• Formerly known as Erdheim' s medionecrosis aortica cystic
• frequency of cerebral stroke with aortic dissection has varied from 10 to 50
percent and that of spinal stroke has been approximately 10 percent
• frequently in men
• late thirties or early forties
• spontaneous event or arises in relation to a whiplash injury, bouts of violent
coughing, or direct trauma to the head or neck, which need not be severe-e.g.,
being struck in the neck by a golf or tennis ball
• Ehlers-Danlos and Marfan syndromes, osteogenesis imperfecta,
Loeys-Dietz syndrome (transforming growth factor [TGF]-,B
receptor mutation), and alpha1 -antitrypsin deficiency are also
associated with an increased risk of vascular dissection
• two distinct syndromes:
• (1) unilateral headache associated with an ipsilateral Horner syndrome,
essentially the Raeder syndrome
• (2) unilateral headache and delayed focal cerebral ischemic symptoms
• dissection of the internal carotid artery can be detected by ultrasonography
and confirmed by MRl and CTA, which show a double lumen within the vessel
on axial MRl sections
• Arteriography by any of these methods, including by conventional
angiography usually reveals an elongated, but variable length, irregular
narrow column of dye, usually beginning 1 .5 to 3 cm above the carotid
bifurcation and extending to the base of the skull, a picture that Fisher has
called the string sign
• pathogenesis of spontaneous carotid dissection is at present uncertain
Vertebral Artery Dissection
• Dissection o f these arteries may originate in the neck and extend into the
intracranial portion
• most common identifiable cause - rapid and extreme rotational movement of
the neck
• dissection most commonly originates in the Cl-C2 segment of the vessel,
where it is mobile but tethered as it leaves the transverse foramen of the axis
and turns sharply to enter the cranium
• Suspected if persistent occipitonuchal pain and vertigo or related medullary
symptoms arise following one of the known precipitants-such as chiropractic
manipulation of the neck, head trauma, or Valsalva straining or coughing
activities
 Intracranial Arterial Dissection
• purely intracranial dissection of the middle cerebral or basilar arteries, there is usually no
preceding trauma, but a few patients have had minor head injuries, extreme coughing, or
other recently Valsalva-producing events (e.g., after childbirth)—or they had used cocaine
• typical picture is of fluctuating symptoms referable to the affected circulation and severe
cranial pain on the side of the occlusion-retroorbital case of middle cerebral
dissection, occipital in the case of basilar dissection, occipital combined with
supraorbital in the case of vertebral dissection
Treatment of Cervical Artery Dissection
• primarily with anticoagulation for several weeks or months and followed up
with some form of arteriography
Moyamoya Disease
• Moyamoya is a Japanese word for a "haze," "puff of smoke“
• it has been used to refer to an extensive basal cerebral rete
mirabile - network of small anastomotic vessels at the base of the
brain around and distal to the circle of Willis, seen in carotid
arteriograms, associated with segmental stenosis or occlusion of
the terminal intracranial parts of both internal carotid arteries
• predominant in, but not limited to the Japanese
• United States, Western Europe, and Australia
• hemoglobinopathies, particularly sickle cell anemia, may cause a
vasoocculsive condition equivalent to moyamoya disease, possibly because of
sickling of red blood cells in the vasa vasorum of the supraclinoid carotid
artery
• association between moya moya, Down syndrome, and certain human
leukocyte antigen (HLA) types favors a hereditary basis
• autosomal dominant pattern with incomplete penetrance due to a site on
chromosome 17q
• symptom that led to medical examination was usually a sudden weakness of
an arm, leg, or both on one side
• symptoms tended to clear
• rapidly but recurred in some instances. Headache, convulsions, impaired
mental clarity, visual disturbance, and nystagmus were less frequent
• In older patients, subarachnoid hemorrhage was the most common initial
manifestation
• Treatment
– surgical measures have been employed, including transplantation of a
vascular muscle flap, omentum, or pedicle containing the superficial
temporal artery to the pial surface of the frontal lobe temporal pial
synangiosis with the idea of creating neovascularization of the cortical
convexity
Binswanger Disease
• denote a widespread degeneration of cerebral white matter having a vascular
causation and observed in the context of hypertension, atherosclerosis of the
small blood vessels, and multiple strokes

• Main features:
– Dementia
– pseudobulbar state
– gait disorder
(alone or in combination)
Familial Subcortical Infarction
(CADASIL and CARASIL)
• imaging appearance of large confluent cerebral white matter changes somewhat similar
to Binswanger leukoencephalopathy
• autosomal dominant familial trait linked in several families to a missense mutation on
chromosome 19
• hereditary multiinfarct dementia
• CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy)
• recurrent small strokes beginning in early adulthood culminate in
a subcortical dementia
• syndrome of early alopecia and lumbar spondylosismwith the
white matter changes typical of CADASIL has been identified as
a recessively inherited disease (cerebral autosomal recessive
arteriopathy with subcortical infarcts and leukoencephalopathy
[CARASIL])
• missense change on chromosome 19 of the NOTCH 3 gene
• interesting mutation of the COL4Al gene for type 4 collagen leads
to familial small vessel disease and intracerebral hemorrhage in
mice and humans
Strokes in Children and Young Adults
• Ischemic nnecrosis of cerebral tissue can occur in utero, resulting stroke is
usually referred to as congenital hemiplegia
• adjacent ventricular region tends to expand into the stroke cavity and may
cause a porencephalic cyst
• stroke is not an uncommon event in young adults (ages 15 to 45 years),
accounting for an estimated 3 percent of cerebral infarctions in typical series
• Most of the strokes could be accounted for by three categories, more or less equal in
size:
• (1) atherosclerotic thrombotic infarction (usually with a recognized risk factor)
• (2) cardiogenic embolism (particularly in the past association with rheumatic heart
disease, infective and noninfective endocarditis, paradoxic embolism through patent
foramen ovale and other cardiac defects, and prosthetic heart valves)
• (3) one of several nonatherosclerotic vasculopathies (arterial trauma, dissection of the
carotid artery, moyamoya, lupus erythematosus, drug-induced vasculitis)
• Hematologically related disorders-use of oral contraceptives the
postpartum state, and other hypercoagulable states-were the
probable causes in 15%
• presence of antiphospholipid or anticardiolipin antibodies (lupus
anticoagulant) - majority of these patients are women in their
thirties without manifest systemic lupus erythematosus
• Wolf and colleagues identified a prolonged aura in young women with an established
history of migraine as a risk for strokes - the posterior circulation
• Overall, in children and young adults with ischemic stroke, the main diagnoses to be
considered are:
–carotid and vertebral dissection
–drug abuse (mainly cocaine)
–thrombosis induced by contraceptive estrogens
–antiphospholipid antibody syndrome
–cardiac disease
–patent foramen ovale (PFO)
Oral Contraceptives, Estrogen,
and Cerebral Infarction
• women who take oral contraceptives in the childbearing years-particularly if
they are older than 35 years of age and also smoke, are hypertensive, or have
migraine--are at increased risk of cerebral infarction
• increased risk of stroke are women taking high-dose (0.50-mg) estrogen pills
Stroke in Pregnancy and the Postpartum
Period
• risk of both cerebral infarction and intracerebral hemorrhage appears to be
mainly in the 6-week period after delivery rather than during the pregnancy
itself
• Most of the focal vascular lesions during pregnancy were a result of arterial
occlusion in the second and third trimesters and in the first week after delivery
• Venous occlusion tended to occur 1 to 4 weeks postpartum
• occurrence of paradoxical embolus is always a consideration in pregnancy
because of a tendency to form clots in the pelvic and leg veins, coupled with
increased right heart pressures
Stroke With Cardiac Surgery
• immediate neurologic disorder consisted of a delay in awakening from the
anesthesia; subsequently there was slowness in thinking, disorientation,
agitation, combativeness, visual hallucinations, and poor registration and
recall of what was happening
• form of a confusional state sometimes verging on delirium or acute psychosis,
usually cleared within 5 to 7 days
• Doppler insonation of the middle cerebral arteries is being studied to detect
transient signals called HITs (high-intensity transients) as a manifestation of
small emboli during surgery but, as for the transients frequently noted during
cerebral arteriogram
INTRACEREBRAL
HEMORRHAGE
• third most frequent cause of stroke, following cerebral embolism and
thrombotic disease
• hypertensive primary ("spontaneous") intracerebral hemorrhage, ruptured
saccular aneurysm and vascular malformation, and hemorrhage associated
with the use of anticoagulants or thrombolytic agents account for the
majority
Primary Intracerebral Hemorrhage
• often devastating
"spontaneous" brain
hemorrhage
• result of chronic hypertension
and degenerative changes in
cerebral arteries
Most common sites of a cerebral
hemorrhage
• 1) the putamen and adjacent internal capsule – 50%
• (2) the central white matter of the temporal, parietal, or frontal
lobes (lobar hemorrhages, not strictly associated with
hypertension)
• (3) the thalamus
• (4) one or the other cerebellar hemisphere
• (5) the pons
• The extravasation of blood into the substance of the brain forms a roughly
circular or oval mass that disrupts the tissue and can grow in volume if the
bleeding continues.
• Adjacent brain tissue is distorted and compressed. If the hemorrhage is large,
midline structures are displaced to the opposite side of the cranium and the
reticular activating and respiratory centers are compromised, leading to coma
and death
• Hydrocephalus may occur as a result of bleeding into the ventricular system
or from compression of the third ventricle.
• On CT, fresh blood is visualized as a white mass as soon as it is shed.
• The "spot sign," the appearance of contrast within the hemorrhage during CT
angiography, is associated with a high rate of hematoma expansion
• After 2 to 3 weeks, the surrounding edema begins to recede and the density
of the hematoma decreases, first at the periphery
• As deoxyhemoglobin and methemoglobin form, the hematoma signal
becomes bright
• If the hemorrhage is large, midline structures are displaced to the opposite
side of the cranium and the reticular activating and respiratory centers are
compromised, leading to coma and death
• Massive refers to hemorrhages several centimeters in diameter, usually larger
than 50 mL; small applies to those 1 to 2 cm in diameter and less than 20 mL
in volume
• The hypertensive vascular lesion that leads t o arteriolar rupture in most cases
appears to arise from an arterial wall altered by the effects of hypertension
Clinical Syndrome
• brain hemorrhage is the most dramatic and from ancient times has been
given its own name, "apoplexy.“
• The prototype was an obese, plethoric, hypertensive male who falls senseless
to the ground-impervious to shouts, shaking, and pinching, breathes
stertorously, and dies in a few hours
• Seizures, usually focal, occur in the first few days in only 10 percent of cases of
supratentorial hemorrhage
• cardinal features and serve most dependably to distinguish hemorrhage
fromischemic stroke: headache, acute hypertension, and vomiting with
hemiplegia
Pontine Hemorrhage
• almost invariably associated with deep coma within a few minutes
• dominated by total paralysis with bilateral Babinski signs, decerebrate
rigidity, and small (1-mm) pupils that react to light. Lateral eye movements,
evoked by head turning or caloric testing, are impaired or absent
Cerebellar Hemorrhage
• usually develops over a period o f 1 or more hours, and loss of consciousness
at the onset is unusual
• Repeated vomiting is a prominent feature, with occipital headache, vertigo,
and inability to sit, stand, or walk
• mild ipsilateral facial weakness, diminished corneal reflex, paresis of
conjugate lateral gaze to the side of the hemorrhage, or an ipsilateral sixth-
nerve weakness occur with larger hemorrhages that compress the pons or
extend into the cerebellar peduncle
• Other infrequent ocular signs include blepharospasm, involuntary closure of
one eye, skew deviation, "ocular bobbing," and small, often unequal pupils
that continue to react until very late in the illness.
• Contralateral hemiplegia and ipsilateral facial weakness occur if there is
marked displacement and compression of the medulla against the clivus.
Lobar Hemorrhage
• Bleeding in areas other than those listed above, specifically in the subcortical
white matter of one of the lobes of the cerebral hemisphere
• Causes:
– Anticoagulation
– Thrombolytic therapy
– acquired coagulopathies
– cranial trauma
– Arteriovenous Malformation
– Trauma
– in the elderly, amyloidosis of the cerebral vessels

• Most lobar hemorrhages are spherical or ovoid, but a few follow the contour
of the subcortical white matter tracts and take the form of a slit
Laboratory Findings
• rapid diagnosis o f intracerebral hemorrhage, the CT occupies the foremost
position
• spot sign on CT angiography has been mentioned above in relation to
hematoma expansion
• MRI is particularly useful for demonstrating brainstem hemorrhages and
residual hemorrhages, which remain visible long after they are no longer
detectable on the CT (after 4 to 5 weeks)
• lumbar puncture is ill advised, for it may precipitate or aggravate an
impending shift of central structures and herniation
• white cell count in the peripheral blood may rise transiently to 15,000/mm3, a
higher figure than in thrombosis, but it is most often normal
• lumbar puncture is ill advised, for it may precipitate or aggravate an
impending shift of central structures and herniation
• white cell count in the peripheral blood may rise transiently to 15,000/mm3, a
higher figure than in thrombosis, but it is most often normal
Course and Prognosis
• immediate prognosis for large and medium-sized cerebral clots
is grave; some 30 to 35 percent of patients die in 1 to 30 days
• A formula that predicts outcome of hemorrhage based on clot
size was devised by Broderick and coworkers (1993); it is mainly
applicable to putaminal and thalamic clots
• A volume of 30 mL or less, calculated by various methods from the CT
predicted a generally favorable outcome

• A clot 60 mL in volume is almost uniformly fatal if situated in the

basal ganglia but may allow reasonably good outcome if located in the frontal
or occipital lobe
• There is no need to administer anticonvulsive
medication unless a seizure has occurred
Treatment
• Management of patients with large intracerebral hemorrhages and coma
includes the maintenance of:
– adequate ventilation
– selective acute use of controlled hyperventilation to a Pco2 of
25 to 30 mm Hg
– Monitoring of intracranial pressure in some cases
– Control by the use of tissue-dehydrating agents such as
mannitol (osmolality kept at 295 to 305 mOsm/L and Na at 145
to 150 mEq)
– limiting intravenous infusions to normal saline
• Rapid reduction of moderately elevated blood pressure (between 140 and 160
mm Hg systolic), in the hope of reducing further bleeding, is not
recommended, because it risks compromising cerebral perfusion in cases of
raised intracranial pressure.
• Sustained blood pressures of greater than 110 mm Hg (generally above 1 60
mm Hg systolic) may exaggerate cerebral edema and perhaps enhance the
risk extension of the clot
• approximately this level of acute hypertension that the use of beta-blocking
drugs (esmolol, labetalol) or angiotensin-converting enzyme (ACE) inhibitors is
recommended
• A large, multicenter, randomized study involving 1 ,033 patients
with supratentorial hemorrhage, under the auspices of the
Surgical Trial in Intracerebral Haemorrhage (STICH) study
reported by Mendelow and colleagues, has failed to show a
benefit from early surgery on survival or neurologic functioning
at 6 months
• clots that were small and close to the surface of the brain may
have benefited from evacuation
• Mayer and coworkers studied the promising approach
of administering clotting factor VII within 4 h of
hemorrhage.
– In a preliminary study, survival was improved and there was a
reduction in enlargement of the hematoma, but their
subsequent series has failed to confirm the benefit on survival
so that infusion of factor VII is not currently part of routine
practice.
• If acute hydrocephalus has resulted from a centrally placed
hemorrhage or rupture into the ventricular system, a drain is
needed
• an ongoing study of the reduction of intraventricular
hemorrhage size by the use of infused tissue plasminogen
activator through a ventricular catheter.
– Preliminary results suggest that this approach may reduce mortality, and
similar practices have been adopted for some time on many neurosurgical
services.
• issue often arises of the appropriate timing of restarting
anticoagulation in patients whose hemorrhage
occurred on warfarin.
• In some instances, such as a prosthetic heart valve
requires warfarin, medication is often reintroduced
after a week or two
Surgical Evacuation of Cerebellar
Hematoma
• surgical evacuation of cerebellar hematomas is a
generally accepted treatment and is a more urgent
matter because of the proximity of the mass to the
brainstem and the risk of abrupt progression to coma
and respiratory failure
• hydrocephalus from compression of the fourth ventricle
more often complicates the clinical picture and further
raises intracranial pressure
• As a rule, a cerebellar hematoma less than 2 cm in
diameter leaves most patients awake and infrequently
leads to deterioration, therefore generally not requiring
surgery
• Hematomas that are 4 cm or more in largest diameter,
especially if located in the vermis, pose the greatest risk
SPONTANEOUS SUBARACHNOID
HEMORRHAGE AND RUPTURED
SACCULAR ANEURYSM
• fourth most frequent cerebrovascular disorder
• also have been called "berry" aneurysms
• take the form of small, thin-walled blisters protruding from arteries of the
circle of Willis or its major branches
• rupture causes a flooding of the subarachnoid space with blood under high
pressure
• As a rule, the aneurysms are located at vessel bifurcations and
branchings and are generally presumed to result from
developmental defects in the media and elastica of the arteries
• alternate theory - aneurysmal process is initiated by focal destruction of the
internal elastic membrane, which is produced by hemodynamic forces at the
apices of bifurcations (Ferguson)
• those that rupture usually have a diameter of 10 mm or more
• site of rupture is usually at the dome of the aneurysm, which may have one or
more secondary sacculations
• Although hypertension is more frequently present than in the general
population, aneurysms most often occur in persons with normal blood
pressure
• 90 to 95 percent of saccular aneurysms lie on the anterior part of the circle of
Willis
Four most common sites:
• (1) the proximal portions of the anterior communicating artery
• (2) at the origin of the posterior communicating artery from the stem of the
internal carotid
• (3) at the first major bifurcation of the middle cerebral artery
• (4) at the bifurcation of the internal carotid into middle and anterior cerebral
arteries
• Mycotic aneurysm - caused by a septic embolus that
weakens the wall of the vessel in which it lodges,
almost always at a site in a distal cerebral vessel, well
beyond the circle of Willis
SAH Clinical Syndrome
Three patterns
(1) the patient is stricken with an excruciating
generalized headache and vomiting and falls
unconscious almost immediately
(2) severe generalized headache develops in the same
instantaneous manner but the patient remains
relatively lucid with varying degrees of stiff neck-the
most common syndrome
(3) rarely, consciousness is lost so quickly that there is no
preceding complaint
• Rupture of the aneurysm usually occurs while the patient is active rather than
during sleep, and in a few instances during sexual intercourse, straining at
stool, lifting heavy objects, or other sustained exertion
• Convulsive seizures, usually brief and generalized, occur in 10 to 25 percent of
cases according to Hart and associates (but far less often in our experience) in
relation to acute bleeding or rebleeding.
• These early seizures do not correlate with the location of the aneurysm and
do not appear to alter the prognosis.
• a cavernous or anterolaterally situated aneurysm on the first part
of the middle cerebral artery, the pain may be projected to the
orbit
• aneurysm on the posteroinferior or anteroinferior cerebellar
artery may cause unilateral occipital or cervical pain
• Partial oculomotor palsy with dilated pupil may be indicative of
an aneurysm of the posterior communicating-internal carotid
junction or at the posterior communicating-posterior cerebral
junction
• large aneurysms just anterior to the cavernous sinus
compress the optic nerves or chiasm, third nerve,
hypothalamus, or pituitary gland
• monocular visual field defect may also develop with a
supraclinoid aneurysm near the anterior and middle
cerebral bifurcation or the ophthalrnic - carotid
bifurcation
• “sentinel headache" - used in an imprecise way
to refer to both a headache that precedes subarachnoid
hemorrhage and to a small leakage prior to a major
rupture
SAH Laboratory Findings
• A C T will detect blood locally or diffusely in the subarachnoid
spaces or within the brain or ventricular system in more than 90
percent of cases and in practically all cases in which the
hemorrhage has been severe enough to cause momentary or
persistent loss of consciousness
• CSF becomes grossly bloody within 30 min or sooner of the
hemorrhage, with RBC counts up to 1 million/ mm3 or even
higher
• diagnosis of ruptured saccular aneurysm is essentially excluded if
blood is not present in the CSF, provided the spinal fluid is
examined more than 30 min after the event
• To determine whether xanthochromia is present, fresh CSF
must be centrifuged in a tube with a conical bottom and the
supernatant compared to clear water in good light or examined
by spectrophotometric techniques
• CSF in the first days is under increased pressure, as high as 500 mm Hp-but
usually closer to 250 mm h20-an important finding in differentiating
spontaneous subarachnoid hemorrhage from a traumatic tap
• Bilateral carotid and vertebral ("four-vessel") angiography - most
dependable means of demonstrating an aneurysm and does so in essentially
all patients who harbor an aneurysm, but in addition to other causes of
subarachnoid hemorrhage, approximately 5 to 10 percent of patients with
aneurysmal rupture will not have an aneurysm evident
Vasospasm
• Delayed hemiplegia and other deficits because of focal
vasospasm usually appear 3 to 10 days after rupture and rarely
before or after this period
• reduction in the caliber of blood vessels (vasospasm) appears to
be a direct effect of some blood product on the adventitia of the
adjacent artery
• clinical features of delayed cerebral vasospasm depend on the affected blood
vessel but typically include a fluctuating hemiparesis or aphasia and
increasing confusion that must be distinguished from the effects of
hydrocephalus
• Transcranial Doppler ultrasonography measurements provide an indirect
way of following, by observations of blood flow velocity, the caliber of the
main vessels at the base of the brain but they are somewhat imprecise for this
purpose
Hydrocephalus
• large amount of blood ruptures into the ventricular system or
floods the basal subarachnoid space, it may find its way into the
ventricles through the foramina of Luschka and Magendie
• Delayed and subacute hydrocephalus as a result of blockage of
the CSF pathways by blood may appear after 2 to 4 weeks and is
managed similarly
Anatomic-Clinical Corrrelations of
Aneurysms
• Collection of blood in the anterior interhemispheric
fissure - anterior communicating artery aneurysm
• sylvian fissure - middle cerebral artery aneurysm
• anterior perimesencephalic cistern - posterior
communicating or distal basilar artery aneurysm
Localization
• (1) third-nerve palsy (ptosis, diplopia, dilatation of
pupil, and divergent strabismus) - indicates an
aneurysm at the junction of the posterior
communicating artery and the internal carotid artery,
the third nerve passes immediately lateral to this point
or at the posterior cerebral-posterior communicating
arteryjunction
• 2) transient paresis of one or both of the lower limbs at the
onset of the hemorrhage – anterior communicating aneurysm
that has interfered with the circulation in the anterior cerebral
arteries
• (3) hemiparesis or aphasia - aneurysm at the first major
bifurcation of the middle cerebral artery
• 4) unilateral blindness - aneurysm lying anteromedially in the
circle of Willis (usually at the origin of the ophthalmic artery or at
the bifurcation of the internal carotid artery
• (5) state of retained consciousness with akinetic mutism or
abulia - anterior communicating artery
• (6) the side on which the aneurysm lies may be indicated by a
unilateral preponderance of headache or by unilateral preretinal
(subhyaloid) hemorrhage (Terson syndrome)
• occurrence of monocular pain, or, rarely, lateralization of an
intracranial sound heard at the time of rupture of the aneurysm
• Sixth-nerve palsy, unilateral or bilateral, is usually attributable to
raised intracranial pressure and is less often of localizing value
• Bilateral Babinski signs are found in the first few days following rupture if
there is hydrocephalus
• Fever up to 39°C (102.2°F) may be seen in the first week, but most patients
are afebrile.
Systemic Changes Associated
With Subarachnoid Hemorrhage
• Acute subarachnoid hemorrhage is associated with several
characteristic responses in the systemic circulation, water
balance, and cardiac function
• ECG changes include symmetrically large peaked T waves
("cerebral T waves") and other alterations, suggesting
subendocardial or myocardial ischemia
Rebleeding and Prognosis
• tendency for the hemorrhage to recur from the same site in
more than one-third of patients, often catastrophically
Treatment
• influenced b y the neurologic and general medical state of the patient as well
as by the location and morphology of the aneurysm
Hunt and Hess
• Grade I. Asymptomatic or with slight headache and stiff neck
• Grade II. Moderate to severe headache and nuchal rigidity but no focal or
lateralizing neurologic signs
• Grade III. Drowsiness, confusion, and mild focal deficit
• Grade IV. Persistent stupor or semicoma, early decerebrate rigidity and
vegetative disturbances
• Grade V. Deep coma and decerebrate rigidity
Giant Cerebral Aneurysms
• congenital anomalies
• by definition greater than 2.5 cm in diameter, but sometimes
twice or more as large
• Most are located on a carotid, basilar, anterior, or middle
cerebral artery, but also are found on the vertebral artery
• Treatment of saccular aneurysms is surgical if the lesion is
symptomatic and it is accessible; endovascular techniques have
been employed if the lesion is in the vertebral or midbasilar
artery
Mycotic Aneurysm
• term mycotic aneurysm designates an aneurysm caused by a localized
bacterial or fungal inflammation of an artery
• Osler introduced the misnomer mycotic aneurysm to describe an infectious
process in the wall of a vessel
• Peripheral arteries are involved more often than intracranial ones; about two
thirds of the latter are associated with bacterial endocarditis caused by
streptococcal infections
• usual pathogenic sequence is an embolic occlusion of a small artery, which
may announce itself clinically by an ischemic stroke with white blood cells in
the CSF
• Antibiotic or antifungal treatment is usually continued for at least 6 weeks
Convexity Subarachnoid Hemorrhage
• causes for this bleeding are numerous, the most obvious being cranial trauma
but a diversity of processes may be responsible including cerebral amyloid
angiopathy, reversible cerebral vasoconstriction syndrome, cortical vein
thrombosis, the use of cocaine, cavernous angioma, dural arteriovenous
fistula, and posterior reversible leukoencephalopathy
ARTERIOVENOUS MALFORMATIONS
OF THE BRAIN
• consists of a tangle of dilated vessels that form an abnormal communication
between the arterial and venous systems
• developmental abnormalities represent persistence of an embryonic pattern
of blood vessels and not a neoplasm
• Venous malformations, consisting purely of distended veins deep in the white
matter, are a separate entity; they may be the cause of seizures and
headaches but seldom of hemorrhage
• True vascular malformations vary in size from a small blemish a few
millimeters in diameter lying in the cortex or white matter to a huge mass of
tortuous channels constituting an atrioventricular (AV) shunt of sufficient
magnitude to raise cardiac output
• When hemorrhage occurs from an AVM, blood may enter the subarachnoid
space, producing a picture almost identical to that of a ruptured saccular
aneurysm, but generally less severe
• AVMs are about one-tenth as common as saccular aneurysms
• equally frequent in males and females
• two lesions-AVM and saccular aneurysm (on the main feeding artery of the A
VM)-are associated in approximately 5 percent of cases; the conjunction
increases with the size of the AVM and the age of the patient
Clinical Features
• Bleeding or seizures are the main modes of presentation
• lesion is present from birth
• onset of symptoms is most common between 10 and 30 years of age
• first clinical manifestation is a cerebral subarachnoid hemorrhage; in 30
percent, a seizure is the first and only manifestation; and in 20 percent,
the only symptom is headache
• Most of the malformations associated with migraine-like headaches lie in
the parietooccipital region patients have a family history of migraine
• "intracerebral steal“ can result in hypoperfusion of the surrounding brain
• the size, location, and venous drainage characteristics of a cerebral AVM for
surgical planning, Spetzler and Martin devised a widely used grading
scale
• summed score gives guidance as to the difficulty in surgical removal and has a
less certain relationship to the clinical behavior of the lesion
– Lesions 1 to 3 mm are considered small, and give 1 point
– 3 to 6 mm are medium sized and 2 points
– over 6 mm are large and assigned 3 points
– location in an eloquent site gives 1 point and
– venous drainage to the deep veins gives another point (the summed score is
between 1 and 5)
Treatment
• preferred approach in most centers is surgical excision
• Spetzler-Martin Scale gives guidance as to the surgical difficulty and risk
• Grades IV and V - not resected
• Grade III - approached surgically but often with preceding interventional
embolization of parts of the lesion
• Inaccessible lesions, attempts have been made to obliterate the malformed
vessels by ligation of feeding arteries or by the use of endovascular
embolization with liquid adhesives or particulate material that is injected via a
balloon catheter that has been navigated into a feeding vessel
• radiosurgery are used to decrease the size of the lesion
• utilized most often with A VMs of 3 cm or smaller located in an
area of the brain in which resection would be likely to produce a
serious neurologic disability
• technique of radiosurgery has been adopted by others using
photon radiation sources, such as a linear accelerator, gamma
Knife, and other modes of focused x-ray radiation as accepted
alternatives to operative treatment of lesions situated in deep
regions
• Two types of complications of radiation:
– delayed radiation necrosis, which is predictable based on the
radiation dose
– venous congestion that occurs several weeks or months after
treatment
Dura l Arteriovenous Fistula
• curious vascular abnormalities, occurring in both the cranial and spinal dura,
have different presentations at each site
Spinal form:
• more common in general experience
Cranial type:
• detected with increasing frequency as refinements continue to be made in
imaging of the cerebral vessels
• defining features are radiologic-a nidus of abnormal arteries and veins with
arteriovenous shunting contained entirely within the leaflets of the dura
• lesion is usually fed by dural arterial vessels derived from the internal cranial
circulation and often, more prolifically, from the external cranial circulation
(external carotid artery and muscular branches of the vertebral artery)
• Venous drainage of these lesions is often complex and is largely directed to
the dural venous sinuses
Cavernous Malformations (Cavernoma)
• Vascular malformations composed mainly o f clusters of thin-
walled veins without important arterial feeders and with little or
no intervening nervous tissue make up a significant group, some
7 to 8 percent of AVMs
• one-half of all cavernous angiomas lie in the brainstem
Treatment
• can be plucked out like blackberries, with low morbidity and mortality
• that cause recurrent bleeding and are surgically accessible with little risk are
often removed
Deep (Developmental) Venous Anomaly
• most common cerebral vascular malformation,
estimated to occur in almost 3 percent of large
autopsy series
• defining characteristics are of a caput medusa
draining into a small collecting vein
Other Causes of Intracranial Bleeding and
Multiple Cerebral Hemorrhages
• anticoagulant therapy - next in frequency to hypertension, is currently the
most common cause of cerebral hemorrhage
• When the bleeding is precipitated by warfarin therapy, treatment with fresh-
frozen plasma and vitamin K, sometimes prothrombin complex concentrate
(PCC) and similar products, which contains clotting factors, is recommended.
• Thrombolytic drugs in the treatment of stroke or myocardial infarction is
complicated by intracranial hemorrhage in 6 - 20 percent of cases
• primary hematologic disorders - leukemia, aplastic anemia, and
thrombocytopenia
• liver disease - uremia that is being treated with dialysis, and lymphoma
• Hemorrhage into primary and secondary brain
tumors - Choriocarcinoma, melanoma, renal
cell and bronchogenic carcinoma, pituitary
adenoma, thyroid cancer, glioblastoma
multiforme, intravascular lymphoma, carcinoid,
and medulloblastoma may present in this way
• brain purpura (pericapillary encephalorrhagia) -
incorrectly referred to as "hemorrhagic encephalitis,"
consists of multiple petechial hemorrhages scattered
throughout the white matter
Cerebral Amyloid Angiopathy
• consists of the deposition of amyloid in the media and adventitia of small
vessels, predominantly in the meninges, cortex, and cortical penetrating
vessels
• There is a propensity for hemorrhages in the posterior parts of the brain. A
strong association has been found with the homozygous APOE £4/£4
genotype
HYPERTENSIVE ENCEPHALOPATHY
POSTERIOR REVERSIBL ENCEPHALOPATHY SYNDROM [PRES], REVERSIBLE
POSTERIOR LEUKOENCEPHALOPATHY [RPLE] )
• term applied to a relatively rapidly evolving syndrome of severe hypertension
in association with headache, nausea and vomiting, visual disturbances,
confusion, and-in advanced cases-stupor and coma
• Neurologic syndrome is usually dominated by symptoms referable to the
occipital and adjacent parietal region
• Clustering of multiple
microinfarcts and
petechial hemorrhages
(the basic
neuropathologic changes
in hypertensive
encephalopathy) in one
region may occasionally
result in a mild
hemiparesis, aphasic
disorder, or rapid failure or
the above-noted
distortion of vision

Main feature is a bilateral increase in T2 signal intensity in the white matter on

MRI and a corresponding reduced density on CT, usually concentrated in the
posterior part of the hemispheres
DIFFUSE CEREBRA L VASOSPASM
• (REVERSIBLE CERE BRAL VASOCONSTRICTIO N SYN DROM E [RCVS],
CALL-FLE M I N G SYN DROM E)
CEREBRAL VASCULITIS
• Infectious Vasculitis
• Inflammatory diseases of the blood vessels that are of infectious origin
• meningovascular syphilis, tuberculous meningitis, fungal meningitis, and the
subacute (untreated or partially treated) forms of bacterial meningitis may be
accompanied by inflammatory changes in the walls of vessels that pass
through the subarachnoid space and result in occlusion of the arteries or veins
• Typhus, schistosomiasis, mucormycosis, aspergillosis , malaria, a n d
trichinosis are infrequent causes o f inflammatory arterial disease, which,
unlike the above-mentioned infections, are not secondary to meningeal
infections
• typhus and other rickettsial diseases - capillary and arteriolar changes and
perivascular inflammatory cells are found in the brain; presumably they are
responsible for the seizures, acute psychoses, cerebellar syndromes, and
coma
• Mucormycosis - internal carotid artery may be secondarily occluded in
diabetic patients as part of the orbital and cavernous sinus infections
• Trichinosis
• Cerebral malaria - convulsions, coma, and, sometimes, focal symptoms
appear to be due to the blockage of capillaries and precapillaries by masses of
parasitized red blood corpuscles
• Schistosomiasis - invade cerebral or spinal arteries
Noninfectious Inflammatory Diseases
of Cranial Arteries
• Included under this heading is a diverse group of arteritides that have little in
common except their tendency to involve the cerebral vasculature
• larger caliber vessels - giant cell arteritides-extracranial (temporal) arteritis,
granulomatous arteritis of the brain, and aortic branch arteritis, one form of
which is known as Takayasu disease
• medium- and smaller-sized vessels - polyarteritis nodosa, the Churg-Strauss
type of arteritis, Wegener granulomatosis, systemic lupus erythematosus,
Behcet disease, hypersensitivity angiitis, Kohlmeier-Degos disease, and the
small vessel disorder of Susac syndrome
Temporal Arteritis (Giant Cell Arteritis,
Cranial Arteritis)
• common among older persons
• arteries of the external carotid system, particularly the temporal
branches, are the sites of a subacute granulomatous
inflammatory exudate consisting of lymphocytes and other
mononuclear cells, neutrophilic leukocytes, and giant cells
• most severely affected parts of the artery usually become
thrombosed
• Occlusion of branches of the ophthalmic artery (mainly those to the posterior
ciliary artery and the choroidal circulation that supply the anterior optic
nerve) results in blindness in one or both eyes, is the most feared
complication, often unpredictably
• administration of prednisone, 50 to 75 mg/ d, provides striking relief of the
headache and polymyalgic symptoms within days and sometimes within
hours, and also prevents blindness
Intracranial Granulomatous Arteritis
• clinical aspects
have taken diverse
forms, sometimes
presenting as low-
grade, nonfebrile
meningitis with
sterile CSF followed
by infarction of one
or several parts of
the cerebrum or
cerebellum
• most important considerations in this disease is the cerebral arteritis caused
by varicella zoster virus of the ophthalmic division of the trigeminal nerve; it
simulates in radiographic appearance granulomatous arteritis and giant cell
arteritis.
Takayasu Disease ( "Pulseless Disease " )
• nonspecific chronic arteritis involving mainly the aorta and the large arteries
arising from its arch
• Most of the patients have been young Asian women, but there are now numerous
reports of similar cases from the United States, Latin America, and Europe
• Constitutional symptoms such as malaise, fever, anorexia, weight loss, and night
sweats usually introduce the illness
• erythrocyte sedimentation rate is elevated in the early and active stages
• Later there is evidence of occlusion of the brachiocephalic, subclavian, carotid,
vertebral, and other arteries that may be asymptomatic or cause neurologic
ischemic symptoms
• The affected arteries no longer pulsate, hence the descriptive term pulseless
disease.
• Coolness of the hands and weak radial pulses are common indicators of the
disease and headaches are frequent. Blurring of vision, especially upon
physical activity or fever, dizziness, and hemiparetic and hemisensory
syndromes are the usual neurologic manifestations
• patients die in 3 to 5 years
Polyarteritis Nodosa and Churg-Strauss
Angiitis of Cerebral Vessels
• inflammatory necrosis o f arteries and arterioles throughout the body in this
disease rarely affects the central (in contrast to frequent involvement of the
peripheral) nervous system
• lungs are usually spared, which is the basis of distinguishing polyarteritis
vasculitis from the Churg-Strauss granulomatous angiitis
• clinical manifestations vary and have included headache, confusion and
fluctuating cognitive disorders, convulsions, hemiplegia, and brainstem signs
Wegener Granulomatosis
• rare disease o f unknown cause, affecting adults as a rule and favoring males
slightly
• subacutely evolving vasculitis with necrotizing granulomas of the upper and
lower respiratory tracts followed by necrotizing glomerulonephritis are its
main features
Neurologic complications:
• 1) a peripheral neuropathy either in a pattern of polyneuropathy or, far more
frequently, in a pattern of mononeuropathy multiplex
• (2) multiple cranial neuropathies as a result of direct extension of the nasal
and sinus granulomas into adjacent upper cranial nerves and from adjacent to
pharyngeal lesions to the lower cranial nerves
• degree of therapeutic success in this formerly fatal disease has been achieved
by the use of cyclophosphamide, chlorambucil, rituximab, or azathioprine
Systemic Lupus Erythematosus
• central nervous system (CNS) was affected in 75 percent of cases
• Hemiparesis, paraparesis, aphasia, homonymous hemianopia, movement
disorders (chorea), and derangements of hypothalamic function occur but
have been infrequent in our experience
• Larger infarcts are usually traceable to emboli from Libman-Sacks (a form of
nonbacterial thrombotic) endocarditis
Arteritis Symptomatic of Underlying Systemic
Disease and Sympathomimetic Drug Ingestion
• True cerebral or spinal cord vasculitis can occur in association
with systemic lymphoma, particularly with Hodgkin disease
• Seizures and death may occur as a result of a syndrome of
delirium and extreme hyperthermia.
• distinction should be made between the complications of
cocaine hydrochloride (the usual form of ingestible cocaine) and
the alkaloid form, or "crack cocaine."
• The former, when injected intravenously more so than when
used intranasally, is prone to cause cerebral hemorrhage as a
result of acute hypertension, similar to the bleeding
• Strokes with crack cocaine, however, are more often ischemic,
typically involving the territory of a large vessel
Susac Syndrome
• another poorly understood form of vasculitis, consisting of a microangiopathy
affecting mainly the brain and retina
• Psychiatric symptoms, headache, dementia, sensorineural deafness, vertigo,
and impairments of vision
• Funduscopy (multiple retinal artery branch occlusions) and retinal
angiography manifest evidence of the vasculopathy
Behcet Disease
• chronic, recurrent vasculitis, involving small vessels, with
prominent neurologic manifestations
• most common in Turkey, where it was first described, in other
Mediterranean countries, and in Japan
• triad of relapsing iridocyclitis and recurrent oral and genital ulcers,
but it is now recognized to be a systemic disease with a much
wider range of symptoms, including erythema nodosum,
thrombophlebitis, polyarthritis, ulcerative colitis, and a number
of neurologic manifestations, some of them encephalitic or
meningitic in nature
• neurologic symptoms usually have an abrupt onset and are
accompanied by a brisk spinal fluid pleocytosis (lymphocytes or
neutrophils may predominate), along with elevated protein but
normal glucose values (in one of our patients, 3,000 neutrophils
per cubic millimeter were found at the onset
• A pathergy skin test - formation of a sterile pustule at the site of a needle
prick-is listed as an important diagnostic test
THROMBOSIS OF CEREBRAL VEINS
AND VENOUS SINUSES
• Thrombosis of the cerebral venous sinuses, particularly of the superior
sagittal or lateral sinus and the tributary cortical and deep veins, gives rise to
a number of important neurologic syndromes
• Cerebral vein thrombosis may develop in relation to infections of the adjacent
ear and paranasal sinuses or to bacterial meningitis
• Occlusion of cortical veins that are the tributaries of the dural sinuses takes
the form of a venous infarctive stroke
• Hypercoagulable conditions • factor V Leiden mutation,
• cancer (particularly of the pancreas protein S or C deficiency
and colon and other
adenocarcinomas) • Antithrombin ill deficiency

• cyanotic congenital heart disease • resistance to activated protein C

• cachexia in infants • primary or secondary

polycythemia
• sickle cell disease
• Thrombocythemia
• Antiphospholipid antibody syndrome
• paroxysmal nocturnal
• Behcet disease
hemoglobinuria.
• administration of drugs such as tamoxifen, bevacizumab, and erythropoietin,
and even the hypercoagulable reaction to heparin that is associated with
thrombocytopenia have all been cited as risks for cerebral venous thrombosis
Cortical Vein Thrombosis (Superficial
Thrombosis of Cortical Veins)
• signature features of isolated thrombosis of superficial cortical veins are the
presence of large superficial (cortex and subjacent white matter) hemorrhagic
infarctions and a marked tendency to focal seizures
Dural Sinus Thrombosis
• Sagittal and Transverse (Lateral) Sinus Thrombosis
• intracranial hypertension with headache, vomiting, and papilledema may
constitute the entire syndrome
• this is the main consideration in the differential diagnosis of pseudotumor
cerebri
• common imaging feature - bilateral superficial paramedian parietal or frontal
hemorrhagic infarctions or edematous venous congestion
• CT with contrast infusion in axial images, a lack of dye opacification in the
posterior sagittal sinus can be observed with careful adjustment of the
viewing window ("empty delta sign").
• Once a venous thrombosis becomes established for several days or longer,
the tributary surface veins take on a "corkscrew" appearance that is
appreciated on the venous phase of an angiogram
Cavernous Sinus Thrombosis
• marked chemosis and proptosis, corresponding to a clot in the anterior
portion of the sinus and there may be disordered function of cranial nerves III,
IV, Vl, and the ophthalmic division of V when the posterior portion is affected
• Spread:
• inferior petrosal sinus - palsies of cranial nerves Vl, IX, X, and XI may result
• superior petrosal sinus - fifth nerve palsy
Deep Cerebral Vein Thrombosis
• Occlusion of the vein of Galen and of the internal cerebral veins is the least
common and clinically most obscure of the venous syndrome
Treatment of Cerebral Venous Thrombosis
• Anticoagulant therapy beginning with heparin or an equivalent for several
days, followed by warfarin, and combined with antibiotics if the venous
occlusion is infectious
• overall mortality rate remains high, with large hemorrhagic venous
infarctions found in 10 to 20 percent of cases
• local infusion of tPA has been used, but not subjected to the same
randomized testing
• Thrombolytic therapy by local venous or systemic infusion has been
successful in small series of cases
STROKE DUE TO HYPERCOAGULABLE
STATES
• Non-bacterial Thrombotic ( Marantic) Endocarditis
– Sterile vegetations, referred to also as nonbacterial thrombotic endocarditis, consist
of fibrin and platelets and are loosely attached to the mitral and aortic valves and
contiguous endocardium
– common source of cerebral embolism
Stroke as a Complication of
Hematologic Disease
• Disseminated Intravascular Coagulation
• most common and most serious disorder of coagulation
affecting the nervous system
• release of thromboplastic substances from damaged tissue,
resulting in the activation of the coagulation process and the
formation of fibrin, in the course of which clotting factors and
platelets are consumed
• essential pathologic change in DIC is the occurrence of widespread fibrin
thrombi in small vessels, resulting in numerous small infarctions of many
organs, including the brain
• main reason for the hemorrhage is the consumption of platelets and various
clotting factors that occurs during fibrin formation, fibrin degradation
products have anticoagulant properties of their own
Antiphospholipid Antibody (Hughes)
Syndrome
• Phospholipids are a family of lipoproteins that influence clotting
• Some of the phospholipids with which the antibodies react are
shared with clotting factors, particularly prothrombin.
Autoantibodies directed at the binding protein of phospholipids
thereby induce blood clotting.
• first of the antibodies to be described were lupus anticoagulant
and anticardiolipin
• Most classifications of the anti phospholipid syndrome also
include antibodies to p2-glycoprotein 1, a protein that may be
necessary for the binding and procoagulant effect of
anticardiolipin antibodyformal
• criteria for the diagnosis of the syndrome require that an
ischemic event be accompanied by the detection of
autoantibodies on two occasions at least 6 weeks apart
• Testing for this disease consists of detection of IgM, IgG, and mixed
antibodies to each of these three main
– 80 percent of patients with lupus anticoagulant have anticardiolipin antibody but
fewer than 50 percent of those with anticardiolipin antibody have lupus
anticoagulant

• main laboratory feature of the illness is a prolonged partial thromboplastin

time (ptt)
• most frequent neurologic abnormality is a TIA, often taking the form of
amaurosis fugax (transient monocular blindness), with or without retinal
arteriolar or venous occlusion
• mechanism of stroke is not entirely clear and may derive from emboli
originating on mitral valve leaflets similar to nonbacterial thrombotic
endocarditis; alternatively, and more likely in our view, there is a
noninflammatory in situ thrombosis of medium-sized cerebral vessels, as
suggested by the limited pathologic material
Treatment
• Warfarin - definitive therapy, alters the testing for antibodies and several
guidelines recommend confirming the presence of antibodies after an interval
of two weeks before starting treatment
• important to eliminate smoking and estrogen containing compounds, as
these greatly raise the risk of stroke in this syndrome. Aspirin and heparin are
favored in women with recurrent fetal loss related to antiphospholipid
antibody
Thrombotic Thrombocytopenic Purpura

• (TTP, Moschcowitz Syndrome) and Hemolytic Uremic Syndrome

• serious diseases of the small blood vessels combined with microangiopathic
hemolytic anemia characterized by widespread occlusions of arterioles and
capillaries involving practically all organs of the body, including the brain
• Sporadic TTP is caused by an acquired circulating IgG inhibitor of the von
Willebrand factorcleaving protease (termed "a disintegrin and
metalloproteinase with thrombospondin type 1 motif, member 13
[ADAMTS13]“
• A rarer familial form (The UpshawShulman syndrome) is caused by an
inherited deficiency of ADAMTS13.
Main features:
• Fever
• Anemia
• Symptoms of renal and hepatic disease, and thrombocytopenia
– the latter giving rise to the common hemorrhagic manifestations (petechiae and
ecchymoses of the skin, retinal hemorrhages, hematuria, gastrointestinal bleeding,
etc.)
• diagnosis is made by finding a microangiopathic hemolytic anemia in the
context of the characteristic clinical picture
• An assay for ADAMTS13 activity is available using an enzyme-linked
immunosorbent assay but the initiation of treatment usually cannot await
confirmation of the diagnosis
• recommended treatment for TTP is plasma exchange or plasma infusion
Polycythemia Vera, Thrombocytosis, and
Thrombocythemia
• a myeloproliferative disorder of unknown cause, characterized
by a marked increase in RBC mass and in blood volume and often
by an increase in WBCs and platelets
• must be distinguished from the many secondary or symptomatic
forms of polycythemia (erythrocytosis), in which the platelets
and white cells remain normal
• majority of patients with cerebrovascular manifestations have
TIAs and small strokes, but we have seen one case of sagittal
sinus thrombosisplatelet counts above 800,000/mm3 are
• considered to be a form of myeloproliferative disease allied with
polycythemia vera
Sickle Cell Disease
• inherited disease is related to the presence of the abnormal hemoglobin S in
the red corpuscles
• practically limited to persons of central African and certain Mediterranean
origins
• begins early in life and is characterized by "crises“ of infection (particularly
pneumococcal meningitis), pain in the limbs and abdomen, chronic leg ulcers,
and infarctions of bones and visceral organs. Ischemic lesions of the brain,
both large and small, are the most common neurologic complications, but
cerebral, subarachnoid, and subdural hemorrhage may also occur, and the
vascular occlusions may be either arterial or venous
• develop progressive stenosis of the supraclinoid intracranial carotid artery
with consequent collateral formation, producing a syndrome akin to
moyamoya

• In the stroke prevention trial of sickle cell anemia, the risk of first stroke was
reduced by 90 percent in 63 children who received periodic transfusions as
compared to 67 children who received only supportive care
SPECIAL CLINICAL PROBLEMS
IN CEREBROVASCULAR DISEASE
• The following are some of the situations encountered by the authors that
may be of value to students and residents and to nonspecialists in the field
The Patient With a History of an Ischemic
Attack or Small Stroke in the Past
• patient may be functioning normally when examined, but it has been ascertained by the
history or radiologic procedures that a stroke or TIA occurred in the pastis particularly
problematic
• if a surgical procedure is planned
• Initial approach is to establish the patency of the carotid arteries by ultrasonography or
MRA
• If there is a reduction in diameter of greater than 70 percent when compared with an
adjacent normal segment of vessel, and probably if there is a severely ulcerated but not
critically stenotic plaque, carotid surgery (or angioplasty with stenting) is advisable
• a single TIA lasted more than an hour or the neurologic
examination discloses minor signs referable to the region of the
hemisphere affected by the TIA, a search for a source of embolus
is indicated
• The mistake is to ignore the potential significance of a prior
small stroke or TIA
The Patient With a Recent Stroke That May
Not Be Complete
• If hours have passed since the first symptoms of stroke but the syndrome is
fluctuating or advancing, the basic problem is whether:
– a thrombotic infarction (venous or arterial) will spread and involve more brain
tissue
– or if embolic, whether the ischemic tissue will become hemorrhagic or another
embolus will occur
– or if there is an arterial dissection, whether it will give rise to emboli
• Therapies are controversial in most of these circumstances
• In some centers, it is the practice to try to prevent propagation of a thrombus
by administering heparin (or low-molecular-weight heparin) followed by
warfarin
• Attention to adequate cerebral perfusion by omitting the patient's usual
blood pressure medications, assuring adequate hydration and avoiding
hemoconcentration, and potentially utilizing a head-down position may all
assist in stabilizing the situation.
The lnevident or Misconstrued Syndromes
of Cerebrovascular Disease
• Although hemiplegia is the typical manifestation of stroke, cerebrovascular
disease may manifest itself by signs that spare the motor pathways but have
the same serious diagnostic and therapeutic implications
• disregarded is a leaking aneurysm presenting as a sudden and intense
generalized headache lasting hours or days and unlike any headache in the
past
– Examination may disclose no abnormality except for a slightly stiff neck and raised
blood pressure. Failure to investigate such a case by imaging procedures and
examination of the CSF may permit the occurrence of a later massive subarachnoid
hemorrhage
• second nonobvious stroke is one caused by occlusion of the
posterior cerebral artery, usually embolic
– This may not be recognized unless the visual fields are carefully tested at
the bedside. The patient himself may not be aware of the difficulty or will
complain only of blurring of vision or the need for new glasses
• Inapparent stroke that may be mistaken for psychiatric disease
– an attack of paraphasic speech from embolic occlusion of a
branch of the left middle cerebral artery. The patient talks in
nonsensical phrases, appears confused, and does not fully
comprehend what is said to him
– He may perform satisfactorily at a superficial level and offer
socially appropriate greetings and gestures
– Only scrutiny of language function and behavior will lead to the
correct diagnosis
– Infarction of the dominant or nondominant temporal lobe and
rarely of the caudate may produce an agitated delirium with few
focal findings. This may be mistaken for a toxic or withdrawal
state
• Parietal infarctions on either side (usually nondominant
hemisphere) are often missed because the patient is entirely
unaware of the problem or the symptoms create only a subtle
confusional state, drowsiness, or only subtle problems with
calculation, dialing a phone, reaching accurately for objects, or
loss of ability to write
• Extinction of bilaterally presented visual or tactile stimuli gives a
clue; marked asymmetry of the optokinetic nystagmus response
is sometimes the only definite sign.
• cerebellar hemorrhage may at first be difficult to recognize as a
stroke
• An occipital headache and complaint of dizziness with vomiting
may be interpreted as a labyrinthine disorder, gastroenteritis, or
myocardial infarction
• A slight ataxia of the limbs, inability to sit or stand, and mild
gaze paresis may not have been properly tested or have been
overlooked. The entire syndrome may be missed if the patient is
not asked to get off the gurney and walk
The Comatose Stroke Patient
• most common causes of vascular coma are intracranial
hemorrhage-usually deep in the hemisphere, less often in the
cerebellum or brainstem, extensive subarachnoid hemorrhage,
and basilar artery occlusion
• brain edema surrounding a large infarction in the territory of the
middle cerebral artery or adjacent to a hemorrhage may
compress the midbrain and produce the same effect
• Certain remedial surgical measures are still available in these
circumstances:
– drainage of blood from the ventricles, shunting of the ventricles in
cases of secondary hydrocephalus due to obstruction of the third
ventricle or aqueduct, evacuation of a cerebral hemorrhage in cases
of recent decline into stupor and coma, and hemicraniectomy in the
case of massive stroke edema
Seizures Following Stroke
• seizures are quite infrequent as the initial manifestation of an ischemic stroke,
and when they do occur in this fashion, an embolus is usually the causative
mechanism
• More often, they are delayed by months or years after the infarction or
hemorrhage
Dementia With Cerebrovascular Disease
• Dementia of the Alzheimer type is often ascribed, on insufficient and
conceptually incorrect grounds, to the occurrence of multiple small strokes
• If vascular lesions are responsible, evidence of an acute stroke episode or
episodes and of focal neurologic deficits to account for at least part of the
syndrome are evident
• there is a process in which diffuse white matter changes on the basis of
vascular disease lead to a less saltatory decline in cognitive function-vascular
dementia
• Several studies have shown an increased incidence or an acceleration of
Alzheimer dementia if there are concurrent vascular lesion