AACN Clinical Issues

Volume 16, Number 4, pp. 421–440

C 2005, AACN

Acute Stroke
Pathophysiology, Diagnosis, and Treatment
Joan Parker Frizzell, PhD, RN

It is most often due to either cellular

ischemia/infarction or intracranial hemor-
Stroke, a neurologic event due to altered rhage. Since it occurs in adults in the mid-
cerebral circulation, is the third leading dle and later years of life, it is responsible
cause of death in the United States. Risk for considerable morbidity and mortality of
factors for stroke include hypertension, older individuals. Risk factors for the occur-
family history, and diabetes mellitus. The rence of a stroke include: hypertension, car-
subtypes of stroke are ischemia, diac arrhythmias, alcohol abuse, and cocaine
infarction, and hemorrhage. Ischemia and abuse. Although stroke can and does occur in
infarction are the result of atherosclerotic infants and children, the focus of this article
development of thrombi and emboli. is the adult population.
Decreased and/or absent cerebral Cerebral ischemia is reduction in blood
circulation causes neuronal cellular injury flow that can last from several seconds to
and death. Intracerebral hemorrhage minutes. Symptoms occur in about 10 sec-
occurs from rupture of cerebral vessels onds due to hypoxia and energy depletion.1,2
often as the result of hypertension. Patient The return of function can occur if blood flow
assessment and diagnosis include the is restored within a few minutes. When the
use of computed tomography scans, symptoms are only transient (ie, less than 24
magnetic resonance imaging, and the hours), this would be considered a transient
National Institute of Health Stroke Scale, ischemic attack (TIA). Infarction or death of
and treatment depends on the etiology of brain tissue occurs if the lack of blood flow
the stroke. Thrombolytic therapy is the lasts for more than a few minutes. In cerebral
mainstay of treatment for thrombotic and infarction, the symptom duration persists due
embolic events. Current recommendations to cell death and often results in permanent
for future stroke care include the disability. The symptoms of cerebral hemor-
development of designated stroke rhage are due to either pressure on surround-
centers. Directions for research in stroke ing tissues or the toxic effects of blood on the
treatment includes examining tissue. The extent of the cellular damage and
neuroprotective therapies. (KEYWORDS: neurologic deficit is determined by actual de-
cerebral hemorrhage, cerebral infarction, struction of neural tissue.3
cerebral ischemia, stroke diagnosis,
stroke pathophysiology, stroke treatment)

From the School of Nursing, La Salle University,

Philadelphia, Pennsylvania.
Reprinted requests to Joan Parker Frizzell, Assis-
tant Professor, School of Nursing, La Salle Univer-
Stroke is an abrupt disturbance in cere- sity, 1900 Olney Ave, Philadelphia, PA 19141 (Frizzell@
bral circulation causing neurological deficits. Lasalle.edu).

421
422
FRIZZELL AACN Clinical Issues

 Epidemiology skull is the foramen magnum, an opening

through which the spinal cord forms a con-
Stoke is the third leading cause of death in the tinuous connection with the brain. The brain
United States accounting for 1 out of every has 3 coverings. They are the pia mater (the
15 deaths. The direct and indirect costs as- innermost layer), the arachnoid (the middle),
sociated with stroke are about $56.8 billion.4 and the dura mater (the outermost, tough
Approximately 700,000 people are diagnosed layer). Pia is directly continuous with the
with a stroke each year, and approximately brain and spinal cord. It is a vascular layer
200,000 of them are experiencing their sec- through with blood vessels pass to the inter-
ond stroke. Men have strokes at a younger nal central nervous system (CNS) to nourish
age than women, therefore the age adjusted the neural tissue. The area between the pia
incidence of stroke is 1.25 times greater for and the avascular arachnoid is the subarach-
men than for women.4 The risk of stroke for noid space, and it contains the cerebral arter-
blacks is almost double that of whites, and ies. The dura is composed of two layers; the
Hispanics have a greater incidence hemor- inner most is referred to as the meninges. The
rhagic stroke at a younger age.5 Most strokes brain contains gray matter and white matter.
(88%) are ischemic events, while other etiolo- Gray matter is external and the myelinated
gies include intracerebral hemorrhage (9%) white matter is internal.
and subacrachnoid hemorrhage (3%).4,6
CEREBRUM: The cerebrum is the largest part of
the brain and is divided into 2 hemispheres
 Risk Factors and consists of 4 lobes: frontal, parietal, tem-
poral, and occipital. On its surface, or cor-
The major or more common risk factors tex, are located the centers from which mo-
for cerebral ischemia and infarction include tor impulses are carried to the muscles and to
family history, hypertension, smoking to- which sensory impulses come from the vari-
bacco, diabetes mellitus, higher body mass ous sensory nerves. It contains an area in its
index, and other risk factors for the develop- inner core referred to as the thalamus. The
ment of atherosclerosis such as hypercholes- thalamus is composed of 2 ovoid structures
terolemia. Smoking increases the risk of a and is an important relay station in the brain.
stroke due to either arterial wall damage and All the main sensory pathways form synapses
atherosclerosis or formation and rupture of with the thalamic nuclei on their way to the
aneurysms. Cardiac risk factors of stroke in- cerebral cortex. These pathways also serve as
clude atrial fibrillation and a recent myocar- vehicles for transmitting pain, emotions, etc.
dial infarction. Evidence of a prior TIA also The location of specific functions within
increases the risk of a stroke. Additionally, the brain is related to the concept of comple-
the risk of having a stroke increases with mentary specialization. The cerebral hemi-
age.7–9 The use of hormonal contraceptives sphere associated with language comprehen-
can also increase the risk of cerebral ischemia sion skills and sequential analytic processes
or infarction.10 The risk of hemorrhagic stroke is referred to as the categorical hemisphere.
is increased in persons of Asiatic or African This was previously referred to as the domi-
decent. Other risk factors include hyperten- nant hemisphere; however, the other cerebral
sion, trauma, advanced age, heavy alcohol hemisphere is not considered to be nondomi-
consumption, and cocaine and amphetamine nant, it just has a different type of specializa-
abuse.4 tion. The other hemisphere focuses primar-
ily on recognition of faces, music, and visual
spatial relationships; therefore, it is referred
 Overview of Anatomy and to as the representational hemisphere.1
Physiology of the Brain For approximately 96% of right-handed in-
dividuals, the left hemisphere is the categor-
ical hemisphere. Thus, the left hemisphere
The Brain
contains areas for language comprehen-
The brain is divided into the cerebrum, cere- sion (Wernicke’s area) and speech and
bellum, and the brain stem. At the base of the word formation (Broca’s area). Injury to
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
423

this hemisphere is associated with language lular structures found in many cells, such as
disorders.1 the nucleolus, microtubules, golgi apparatus,
and rough endoplasmic reticulum. Intracel-
CEREBELLUM AND BRAIN STEM: The cerebellum lular structures specific for neurons include
regulates coordinated activities such as gait neurofilaments, synaptic vesicles, and Nissl
and performance of motor tasks.8 The brain substance.11 Neurons use glucose as their en-
stem includes the midbrain, pons, and ergy source and are dependent on oxidative
medulla oblongata. The midbrain connects metabolism. They produce and release neu-
the pons and the cerebellum with the cere- rotransmitters.
bral hemispheres. The cerebellum is located Neurotransmitters are chemicals synthe-
below and behind the cerebrum. The pons is sized in the neurons that are stored in synap-
located in front of the cerebellum between tic vesicles in the axon terminals. They are re-
the midbrain and the medulla. It serves a leased from the axon terminal by exocytosis
bridge between the 2 halves of the cere- and are also reabsorbed and recycled. These
bellum as well as between the medulla and chemicals cause changes in the cell perme-
the cerebrum. It contains important centers ability of neuron, making it more or less able
for controlling the heart, respiration, and to conduct an impulse.
blood pressure and gives rise to 4 cranial
nerves.2
NEUROGLIA: Neuroglia are the supporting cells
for the neurons of the CNS, whereas Schwann
CEREBRAL CORTEX: Cells appear quite similar,
cells have this function in the peripheral ner-
but functions will vary depending on their
vous system (PNS). The neuroglia comprise
location within the cortex. There are 4 lobes:
about 40% of the brain and spinal cord. They
frontal, parietal, occipital, and temporal. The
outnumber the neurons approximately 4 to 1.
frontal lobes are thought to contain areas as-
Four distinct neuroglia cell types have been
sociated with emotional attitudes and the de-
identified: microglia, ependyma, astroglia,
velopment of thought processes. Nerve fibers
and oligodendroglia. Microglia have phago-
from all portions of the cortex converge in
cytic properties to ingest and digest tissue de-
each hemisphere and make their exit in the
bris. They are found throughout out the CNS
form of tight bundles (“internal capsule”).
and are also believed to have a role in fight-
These cross the corresponding bundle from
ing infection. Ependyma line the ventricular
the opposite side; therefore, a right stroke
system and are involved in the production
means left-sided weakness.
of CSF. Oligodendroglia are the glial cells re-
sponsible for myelin production within the
Cerebrospinal Fluid CNS. Astroglia (astrocytes) are located be-
tween blood vessels and neurons, possi-
Each cerebral hemisphere has a central cav-
bly controlling movement of macromolecules
ity, a ventricle that is filled with clear cere-
between the blood, CSF, and brain as the
brospinal fluid. It traverses from the ventri-
blood-brain barrier. When there is death of
cle through narrow tubular openings to the
neurons due to injury, astrocytes proliferate
subarachnoid space to bathe the entire sur-
and fill in the space formerly occupied by the
face of the brain and spinal cord. The aver-
nerve cell body and its processes. This activ-
age amount of cerebrospinal fluid (CSF) is
ity is known as replacement gliosis.
150 mL.

MYELIN: Myelin is a white lipid-protein com-

Neural Tissue
plex that provides insulation along a nerve
NEURONS: The neuron is the structural, ge- process. It prevents the flow of sodium and
netic, and functional unit of the nervous sys- potassium ions across the neuronal mem-
tem and is composed of cell bodies, den- brane almost completely where it is present.
drites, and axons. The cell bodies are lo- Within the CNS, nerve fibers with myelin
cated in layers on the surface of the brain, sheaths are found within the white matter.
or cortex, and comprise what is referred to Fibers that have no myelin are found within
as gray matter. The neurons contain intracel- the gray matter.
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FRIZZELL AACN Clinical Issues

Cerebral Circulation considered to be continuations of the internal

carotid arteries (see Figure 1).12
The CNS, like all body tissue, is dependent
upon an adequate blood supply for its nu- VERTEBRAL-BASILAR ARTERIAL SUPPLY: Right and
trients and for removal of metabolic waste left vertebral arteries originate from the sub-
products. The arterial blood supply to the clavian arteries of their respective sides. The
brain is complex. However, an understand- vertebrals enter the skull via the foramen
ing of blood flow enables some correlation magnum. At the level of the brainstem, they
of area of injury with symptoms. fuse to form the basilar artery. This continues
to the level of the midbrain where it branches
CAROTID ARTERIAL SUPPLY: On the right, the bra- to form the posterior cerebral arteries.
chiocephalic trunk (innominate) artery di-
vides into the right common carotid and CEREBRAL ARTERIES: Cerebral arteries are clas-
the right subclavian. On the left, the left sified as either penetrating or conducting.
common carotid and left subclavian arter- The conducting arteries form an extensive
ies each arise directly from the aortic arch. network over the surface of the brain. The
There are both internal and external carotid penetrating arteries are nutrient vessels that
arteries that branch off from the common are derived from the conduction arteries.
carotids at about the level of the thyroid They enter the brain at right angles and pro-
gland (carotid sinus). The carotid sinuses re- vide the blood supply for the deep cerebral
spond to changes in arterial blood pressure structures.
to reflexively maintain blood supply to the
brain and the rest of the body. The external ARTERIAL CIRCLE OF WILLIS:The internal caro-
carotids branch off into vessels that supply tids and the vertebral-basilar arteries are 2
the face. The internal carotids enter the skull separate systems delivering blood to the
and divide into the anterior and middle cere- brain. They do however, unite to form the
bral arteries. The middle cerebral arteries are crcle of Willis through a specialized system

Figure 1. Carotid circulation. Reprinted with permission from Book D. Disorders of brain function. In: Porth CM,
ed. Pathophysiology Concepts of Altered Health States. Philadelphia: Lippincott Williams & Wilkins; 2005, 1243.
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
425

Figure 2. Circle of Willis. Reprinted with permission from Book D. Disorders of brain function. In: Porth CM, ed.
Pathophysiology Concepts of Altered Health States. Philadelphia: Lippincott Williams & Wilkins; 2005, 1244.

of communicating arteries. There is usually ergy source.1 Neurons do not store glycogen,
only slight blood flow through these arteries; so energy depletion is rapid.3
however, they serve as a fail-safe mechanism Although glutamate is an excitatory neu-
in case of dramatic changes in arterial blood rotransmitter within the brain, metabolically,
pressure. Collateral circulation may gradually it has a neuroprotective action. It aids in
develop when there is an alteration in normal the removal of the ammonium ion through
blood flow. Most cerebral collateral circula- conversion to glutamine. Since ammonia is
tion is between major arteries via the circle very toxic to brain cells, this glutamate-
of Willis (see Figure 2).12 glutamine conversion serves as a detoxifying
mechanism.1
Brain Metabolism Autoregulation of Blood Flow
Brain metabolism is steady and continuous The normal brain has the ability to regulate its
with no rest periods, requiring a continuous own blood supply to maintain arterial pres-
supply of glucose and oxygen. It is highly sure between 65 and 140 mm Hg.1,2 Factors
depended upon oxygen and accounts for that affect this can be viewed as extrinsic
20% of the body’s oxygen usage.1,2,11 Con- (outside the brain) and intrinsic (inside the
sciousness may be lost in as little as 10 sec- brain).
onds once blood flow has ceased. Dependent The extrinsic factors affecting cerebral
upon oxygen, the brain does not switch to blood flow (CBF) are related primarily to
anaerobic metabolism, and a lapse of even the cardiovascular system and include blood
a few minutes may cause irreversible dam- pressure (BP), cardiovascular function, and
age. Sustained hypoglycemia may also dam- blood viscosity. If systemic mean BP drops
age brain tissue, since glucose is its major en- below 60 mm Hg, the brain’s autoregulatory
426
FRIZZELL AACN Clinical Issues

mechanism becomes less effective. The brain 80% with the blood volume and CSF each
will initially attempt to compensate by ex- comprising 10%. Together, they maintain nor-
tracting more oxygen from the available mal ICP of 50 to 200 mm H2 O (4 to 15 mm
blood supply. If BP continues to drop, signs Hg). Changes in one will cause a compen-
of cerebral ischemia will occur. Alterations satory change in the other to maintain normal
in cardiovascular function that affect cardiac ICP. This is referred to as the Monro-Kellie hy-
output also can reduce CBF. If the cardiac pothesis. The ICP will remain within normal
output is decreased by more than one third, range as long as any increase that occurs does
there is often a fall in CBF. Cerebral blood not exceed the compensatory displacement
flow increases with anemia, but the increased of blood or CSF. If an overcompensatory dis-
viscosity of polycythemia may reduce it by placement occurs, the ICP will rise, result-
50%. ing in cerebral hypoxia, or brain herniation,
The intrinsic factors are influenced by or sideways or downward movement of the
cerebral perfusion pressure. This is the pres- brain. If the CPP falls below 50 mm Hg, cel-
sure difference between the cerebral arter- lular death occurs.2,11
ies and veins. The goal is that cerebral per- When the pressure in the ICP exceeds
fusion pressure will remain constant despite MAP, tissue perfusion falls and demand ex-
changes in systemic BP. Cerebral vascular re- ceeds supply, and cellular hypoxia occurs.
sistance increases or decreases in response The neurons of the cortex are the most sen-
to systemic BP to maintain a constant flow of sitive to changes in oxygenation. That is why
blood to the brain. Cerebral blood vessels are one of the earliest and most reliable signs is
important because of their response in main- “changing level of consciousness.”2
taining constancy of flow. Cerebral blood Increases in ICP cause the CNS ischemic
vessels are under the control of the sympa- response. This is evidenced by a marked in-
thetic nervous system or sympatho-adrenal crease in MAP, reflexive slowing of heart rate,
response. Sympathetic reflexes are believed and widened pulse pressure. This triad of
to cause vasospasm in some types of brain signs, Cushing reflex, is an important but a
damage.1,2 late indicator of increased ICP.2
Intracranial pressure (ICP) is also an im-
portant regulatory mechanism. An increase
 Stroke Subtypes
in ICP will increase cerebrovascular resis-
tance, reducing cerebral blood flow. Cerebral
Ischemia and Infarction
blood flow will not decrease until there is a
considerable increase in ICP.1 ICP is affected Cerebral ischemia and infarction occur from
by these 3 metabolic factors: CO2 concentra- decreased or disrupted blood flow. Ischemia
tion, H+ concentration, and O2 concentration. occurs when there is a decrease in blood flow
High CO2 tension is a strong vasodilator and to less than 20 mL/100 g of brain tissue per
can produce a marked increase in cerebral minute. Reduction of blood flow to less than
blood flow.1 A decreased pH (increased H+ 16 mL/100 g of brain tissue per minute leads
levels) will increase blood flow. Low O2 ten- to tissue death within one hour. In the ab-
sion is a powerful vasodilator, and high O2 sence of blood flow, death of brain tissue
Levels are a moderate vasoconstrictor.2 occurs within 4 to 10 minutes.3
The most common etiology that results
Cerebral Perfusion Pressure
in cerebral ischemia or infarction is local
damage to a vessel wall from atheroscle-
Cerebral perfusion pressure (CPP) is the dif- rosis. This may occur in the aortic arch,
ference between mean arterial blood pres- carotid arteries, or cerebral vessels. The de-
sure (MAP) and the ICP. The normal range is velopment of atherosclerosis begins with en-
60 to 80 mm Hg. dothelial injury and inflammation, leading
to plaque formation. The plaque becomes
MAP − ICP = CPP thick and fibrous with loss of muscle cells.
The sclerotic material partially fills and/or oc-
The cranial cavity contains the brain, cludes the lumen of the vessel. Platelets ad-
blood, and CSF. Of this, the brain takes up here to this, releasing factors that initiate the
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
427

coagulation-clotting cascade, forming a clot

or thrombus. The clot may either break off
as an embolus traveling to a distal vessel or
remain in place, occluding the vessel.8 Lacu-
nar infarcts occur with complete occlusion of
end-arteries that supply a small area of brain
tissue.3 Symptoms from ischemic events oc-
cur fairly rapidly since the brain is very de-
pendent upon adequate oxygen and circu-
lation. Lack of adequate oxygenation to the
cerebral cortex can produce unconsciousness
in a little as 10 seconds.1
Thrombotic events most often affect the
internal carotids, middle cerebral, or basilar
arteries.8,11 Strokes that are the result of em-
boli are frequently considered to be cardiac
in origin. Referred to as cardioembolic stroke,
these account for about 20% of all strokes.3
Although the embolus is from a thrombus
in the either the atria or the ventricle, the
actual thrombus is often not observed. The
diagnosis of a cardiac origin is based on
known cardiac etiology of emboli, such as
atrial fibrillation or recent myocardial infarc-
tion. Cardioembolic strokes most often oc-
clude the middle cerebral artery or the pos-
terior cerebral artery.3 However, emboli may
also develop from the aortic arch or carotid
arteries.8
In contrast to an atherosclerotic event,
symptoms due to an embolus are often
sudden with immediate, noticeable maximal
neurological deficits. In embolic events, the
effected tissue often contains petechial hem-
orrhages, or red infarction (see Figure 3).
The appearance of brain tissue in thrombotic
events is different. With thrombotic ischemia,
the tissue is often paler, or non hemorrhagic
infarct.11
Since atherosclerotic occlusion of the ves-
sel can occur gradually, symptoms are pro-
gressive. The symptoms or deficits increase

−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−→
Figure 3. Gross anatomy of hemorrhagic infarction.
A, Sections of the brain showing a large, discolored,
focally hemorrhagic region in the left middle cere-
bral artery distribution (hemorrhagic, or red, infarc-
tion). B, A hemorrhagic infarction is present in the in-
ferior temporal lobe of the left side of this brain. C,
A bland infarct with punctate hemorrhages, consistent
with ischemia-reperfusion injury, is present in the tem-
poral lobe. Reprinted with permission from Robbins &
Cotran Pathologic Basis of Disease,
c 2005 Elsevier.
428
FRIZZELL AACN Clinical Issues

over several hours to several days. There intracellular calcium levels.3 With depolar-
is a large area of tissue ischemia that in- ization, there is the release of neurotrans-
creases over time. Survival of this ischemic mitters into the synaptic space. Glutamate,
tissue is dependent upon 2 major factors: an excitatory neurotransmitter, accumulates
(1) the availability of collateral circulation at excitatory synapses and in the extracellular
and (2) the duration of the ischemia.11 If space. Glutamate further damages the neu-
the blood flow is not restored, the ischemic rons through overstimulation and opening of
tissue becomes necrotic and cell death oc- membrane channels. The increased influx of
curs. As cerebral blood flow falls to zero, calcium ions and overstimulation ultimately
death of brain tissue can occur within 4 to 10 lead to cell death.1,8,11
minutes.3 Anoxic encephalopathy may occur Cellular death occurs either through irre-
with cerebral thrombosis. The brain distal to versible neuronal cellular damage or through
the clot becomes swollen. There may discol- the apoptotic pathway of programmed cell
oration, with the appearance being “muddy- death. Altered mitochondrial function with
looking” due to changes in the line between increased release of free radicals damages
gray and white matter. As nerve cells disin- cell membranes and alters cellular func-
tegrate, they are replaced by the neuroglia tions. Once the necrotic changes begin,
(gliosis). there is currently no treatment to stop the
At the onset of the cerebral ischemic process.3
event, there is a gradation in brain perfusion. Irreversible changes accompanying cell
Whereas the central area may become in- death include shrinkage of the cell body,
farcted, the surrounding tissue exhibits zones disappearance of the nucleolus, and loss of
of ischemia and injury, the ischemic penum- Nissl substance. Since the cytoplasm stains
bra. The area of ischemia and injury is “at- red with hematoxylin and eosin (H & E) stain-
risk” tissue. The normal cerebral autoregula- ing preparations, they are referred to as red
tion of circulation is not operating and is un- neurons (see Figure 4).11
able to restore blood flow to the area. Unless
treatment is begun immediately, that tissue CLINICAL PRESENTATION: Regardless of the eti-
will become necrotic as well.3 ology, the clinical presentation of symptoms
Ischemia affects both gray and white mat- in a cerebral ischemic/infarction event de-
ter portions of the brain equally, thus the size pend upon: (1) the location of the vessels
of ischemic area is equally distributed. How- and (2) the presence of collateral circula-
ever, the volume of at-risk tissue is greater in tion (see Table 1). However, embolic strokes
gray matter than in white matter. Despite this, have a greater risk of subsequent bleed-
it appears that more white matter is poten- ing into the infarcted area than thrombotic
tially viable and responsive to therapy than strokes.3
gray matter.13
Cerebral infarction is also associated with Lacunar infarcts: These are small cavity in-
cerebral edema. About 5 to 10 stroke patients farcts (usually <15 mm wide) are usu-
develop severe cerebral edema, increasing ally associated with hypertension. They can
the risk of brain herniation.3 be either silent with no associated clini-
cal symptoms or present with very obvious
CELLULAR CHANGES: Acute neuronal injury is symptoms.11 The most common symptoms
the result of CNS hypoxia and ischemia. In- seen with lacunar infarcts are either pure mo-
jured cells respond with a series of reversible tor deficits or pure sensory deficits.8
and irreversible changes. These responses in-
clude recruitment of white blood cell release, The middle cerebral artery:Complete occlusion
inflammatory mediators, and elevation in C of the middle cerebral artery results in loss
reactive protein levels.11,14 of movement and sensation on the contralat-
During ischemic injury, there is failure eral or opposite side of the infarction. How-
of the ion pumps. Potassium flows out of ever, there may be a gaze preference to the
the cell into the extracellular space. The al- ipsilateral or same side as the injury. If this
tered potassium gradient causes depolariza- is the categorical hemisphere, there is also a
tion of neuronal membranes and increased global aphasia.3 If it is the representational
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
429

Figure 4. Cellular changes with cerebral infarction. A, At low magnification, it is possible to see the demarcated
areas of an acute infarction. In the underlying white matter, the areas of infarction are well shown by the myelin stain.
B, Acute ischemic injury causes diffuse eosinophilia of neurons, which are beginning to shrink. C, Infiltration of a
cerebral infarct by neutrophils begins at the edges of the lesion where vascular supply has remained intact. D, After
about 10 days, an area of infarction is characterized by the presence of macrophages and surrounding reactive
gliosis. E, Remote small intracortical infarcts are seen as areas of tissue loss with a small amount of residual gliosis.
Reprinted with permission from Robbins & Cotran Pathologic Basis of Disease,
c 2005 Elsevier.

hemisphere, there is a neglect syndrome, or There are 2 syn-

The posterior cerebral artery:
forgetting that there are 2 sides of the body. dromes observed with occlusion of the pos-
Partial occlusion of the middle cerebral artery terior cerebral artery: P1 and P2. The P1
could include weakness of a hand or arm, fa- syndrome includes the midbrain, subthala-
cial weakness, and partial aphasia.8 mic, and thalamic regions of the brain. The
430
FRIZZELL AACN Clinical Issues

TABLE 1
Clinical Presentation in Ischemic Stroke

Artery Symptoms
Anterior cerebral Weakness and loss of sensation of the contralateral leg and foot
Middle cerebral Contralateral sensory loss and weakness; Loss of the nasal half of vision on the opposite
side and loss of the temporal half of vision on the same side
Categorial hemisphere: aphasia
Representational hemisphere: neglect syndrome
Vertebral Lid lag, with papillary contraction; Ataxia, vertigo, hiccupping, and difficulty swallowing
Basilar Dizziness, double vision, ataxia, hemi- or quadriparesis
Posterior cerebral Memory loss, visual hallucinations, dyslexia, sensory loss, ataxia, altered level of
consciousness

Adapted with permission from Messing RO. Nervous system disorders. In: McPhee SJ, Lingappa VR, Ganong WF, eds.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 4th ed. New York: Lange Medical Books/McGraw-Hill
Medical Publishing Division; 2003:183.

symptoms include a third-nerve palsy with trauma and may occur several hours after the
weakness and ataxia. Extensive infarction initial injury. Subarachnoid hemorrhage can
in this area can result in coma, unreactive occur either as a result of trauma or from the
pupils, and decerebrate rigidity. The P2 syn- rupture of an aneurysm. Intraparenchymal
drome results in injury to the medial temporal hemorrhages usually occur from the rupture
and occipital lobes. This results in memory of small penetrating arteries. They are most
loss, disturbances, or loss of vision on the often the result of hypertension. They usually
contralateral or opposite side of the infarct. occur in the basal ganglia, thalamus, pons,
In some individuals, visual disturbances can and cerebellum. However, they can also oc-
produce hallucinations.3 cur from vascular malformations. Substance
abuse of cocaine and amphetamines results
The basilar artery:The clinical presentation in a rapid increase in blood pressure, leading
seen with occlusion of the basilar artery in- to vessel rupture.8
cludes the “locked-in” state of preserved con- Ruptured cerebral arteries are the usual
sciousness with total quadriplegia. A TIA in source of the bleed.11 Extravasation of blood
this area may produce dizziness or a feeling occurs in the brain and/or the subarach-
of light-headedness.3 noid space. The adjacent tissue may be
displaced and compressed. Movement of
Occlusion of this
Superior cerebellar artery: the blood into the ventricles is associated
vessel causes cerebellar ataxia, partial deaf- with increased morbidity and mortality.3 Ex-
ness, nausea, vomiting, and loss of pain posure to blood irritates and causes va-
and temperature sensation on the opposite sospasms of adjacent vessels. A clot will form
extremities.3 that will eventually resolve and decrease in
size. However, the brain tissue next to the
The symp-
Anterior inferior cerebellar artery: clot can become swollen and necrotic (see
toms seen with occlusion of this vessel in- Figure 5).8
clude ipsilateral deafness, facial weakness, Neurological deficits depend upon the site
and vertigo.3 and severity of the hemorrhage. The onset
is usually abrupt and rapid developing over
30 to 90 minutes. This is often seen in hy-
Cerebral Hemorrhage
pertensive intraparenchymal hemorrhage. In
Cerebral hemorrhage is the third most com- contrast to this rapid onset, bleeding associa-
mon cause of stroke and is associated with tion with anticoagulant therapy will develop
about a 50% mortality rate.3 In addition to in- slowly over 24 to 48 hours. The clinical pre-
traparenchymal hemorrhage, symptoms can sentation can include complaints of: severe
occur from subdural or epidural hematomas. headache, vomiting, nuchal rigidity, stupor,
These are usually the result of some sort of coma, and convulsions. However, almost one
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
431

Figure 5. Hypertensive intraparenchymal hemorrhage. A, Massive hypertensive hemorrhage rupturing into a

lateral ventricle. B, Hypertensive hemorrhage in the pons, with extension to fill the fourth ventricle. Reprinted with
permission from Robbins & Cotran Pathologic Basis of Disease,
c 2005 Elsevier.
432
FRIZZELL AACN Clinical Issues

half of the patients with hypertensive cerebral Stroke, as part of the National Institutes of
hemorrhage die.3 Health, has developed specific criteria to aid
in categorizing deficits due to a stroke.
CELLULAR CHANGES: In acute hemorrhage, the Differential diagnosis should identify the
volume of blood pushes against and com- presence of a TIA or stroke while ruling out
presses the adjacent tissue, ultimately lead- other pathologic processes with symptoms
ing to ischemic injury of that tissue. Even- that could mimic a TIA or stroke. The most
tually, the tissue will be come swollen and common factors would be hypoglycemia,
necrotic. Macrophages begin to phagocytize hyperglycemia, vasculitis, migraine, seizure
the hemorrhagic area within 48 hours of on- disorders, metabolic encephalopathy, recent
set. Both the blood and necrotic tissue are head trauma, and tumors. Thus, diagnostic
phagocytized by the macrophages. As part of blood work would include: complete blood
the inflammatory response, the area is lique- count with platelet count, electrolyte levels,
fied and a cavity is formed. Astrocytes begin blood glucose level, blood urea nitrogen, cre-
to fill in the cavity and new capillaries are atinine, and coagulation studies.3,9,15
formed.11
Computed Tomographic Scan
 Assessment and Diagnosis Computed tomography scans can identify or
exclude a hemorrhage as the cause of the
Any patient with a sudden alteration in neu- stroke. They can also identify neoplasms,
rologic function should be evaluated for a abcesses, or other conditions that can pro-
TIA or stroke. With ischemia or infarction, duce similar symptoms. However, ischemia
it is imperative that thrombolytic therapy be and infarctions may not be evident on a CT
given within 180 minutes of onset of symp- scan during the first 24 hours of the stroke.
toms. Therefore, patients should use the 911 Some infarcts are not evident on CT scan
Emergency Medical Service system for trans- even 48 hours after onset of symptoms. The
port to the nearest hospital that can deter- use of contrast enables visualization of larger
mine the need for and administer tissue plas- cerebral vessels (see Figure 6).3,16 The use of
minogen activator (t-PA).9 a CT scan is often preferred during the acute
There is no reliable clinical presentation phase.15
to differentiate between ischemia, infarc-
tion, and hemorrhage. However, a more de-
Magnetic Resonance Imaging
pressed level of consciousness with an el-
evated blood pressure is more suggestive New advances in imaging studies have en-
of hemorrhage. Improvement of neurologic abled the magnetic resonance imaging (MRI)
deficits would most often indicate ischemia.3 to become an ultrafast imaging method that
Diagnostic criteria are used to provide op- is able examine some of the physiologic as-
timal patient care and treatment during a pects of brain disorders. Diffusion-weighted
stroke. Patients can then be classified ac- imaging (DWI) methods, used as part of the
cording to symptoms and disease progres- MRI study, provide additional information as
sion as well as the underlying etiology of to the extent of the ischemia and irreversible
the event. The initial examination should in- injury.17,18 Therefore, an MRI is able to iden-
clude a full neurological and cardiovascular tify the presence of an infarction within the
assessment. This would include auscultation brain as well as hemorrhagic transformation
of carotid arteries for bruits, comparison of or an ischemic infarct.19 In the future, it will
blood pressure in both arms, and ophthalmo- also be possible to use the MRI to distin-
scopic examination of retina for effects of hy- guish between reversible or irreversible tis-
pertension. Diagnostic testing would include sue injury.17,18
an electrocardiogram (EKG), chest X-ray, uri- An MRI can also be used to determine
nalysis, blood work, and brain imaging in- the presence of a clot or dissection of a
cluding computed tomographic (CT) scan or vessel wall. This can be particularly use-
magnetic resonance imaging (MRI). The Na- ful in diagnosing severe carotid occlusive
tional Institute of Neurological Disorders and disease.18 Additional modification of MRI
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
433

Figure 6. Neuroimaging of middle cerebral artery infarction. A, Computed tomography (CT) scan of the brain of
a patient with a left middle cerebral artery (MCA) stroke of 3 hours duration. As an earliest indicator of infarction,
the “insular ribbon sign” is caused by edema (darker signal) within the left insular cortex and basal ganglia (arrow).
B, Embolic occlusion of the MCA imaged with CT angiography during the acute stroke (arrow). C, Cerebral blood
flow measured with CT perfusion; blood flow is reduced over a wider region of brain than appeared edematous
in A. D, CT angiogram of a carotid artery showing high-grade stenosis (arrow) from atheroma in another patient.
Reprinted with permission from Smith WS, Johnston S, Easton JD. Cerebrovascular diseases. In: Kasper DL, Fauci
AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine, 16th ed. New
York: McGraw-Hill Medical Publishing Division; 2005, 2386.
434
FRIZZELL AACN Clinical Issues

stimulation relaxation rates can provide dif- Of those patients who scores ranged from
ferent types of information about stroke dam- 3 to 4, 57% recovered from the stroke. As
age. These modifications are referred to as expected, only 7% of patient with scores
T1W and T2W. T1W images are more sensi- ranging from 0 to 2 recovered from the
tive for identifying subacute hemorrhage and stroke.21–23
fat structures. T2W images are used to iden-
tify edema, demyelination, infarctions, and
 Treatment
chronic hemorrhage.16 Thus, an MRI is a bet-
ter option for studying cerebral ischemia and
Treatment goals include stabilization of the
infarction.
patient and prevention of further brain in-
jury by improving cerebral perfusion to is-
National Institutes of Health Stroke Scale chemic tissue. The treatment should include
supportive medical therapy. Of utmost im-
The National Institutes of Health Stoke Scale
portance is to maintain a patent airway in the
(NIHSS) was developed as a graded neuro-
event that the patient suffers a loss of con-
logic examination to rate deficits that occur as
sciousness. Both blood pressure and cardiac
a result of a stroke (see Table 2).20 The exami-
rhythm need to be stabilized as well.3 The
nation evaluates motor function, visual fields,
next step in treatment protocol is based on
ataxia, speech, language, cognition, and mo-
the determination as to whether the stroke
tor and sensory impairments. Points are given
is due to a hemorrhage versus a thrombus
for levels of functioning in each of these ar-
or embolus. Therefore, a CT scan should be
eas. The points are then combined for a to-
obtained as soon as possible.
tal score. The higher the score on the scale,
Supportive medical therapy should in-
the greater neurologic deficits present follow-
clude β 1 adrenergic antagonists to reduce
ing a stroke. Training methods have been
the workload of the heart and maintain blood
developed in order to ensure valid and re-
pressure. Since fever and hyperglycemia
producible results when this scale is used to
have been shown to be detrimental to re-
quantify neurologic deficits. Therefore, this
covery, regulation of glucose level and body
score is a fairly reliable measure that can be
temperature is important as well. Blood glu-
used to both evaluate treatment and research
cose levels should be below 200 mg/dL.3
new treatment modalities. It is possible to
correlate the score with the patients’ clinical
Ischemic/Infarction
presentation. Scores <5 indicate mild neuro-
logic impairment, between 5 and 15 indicate Upon determination that the patient is suf-
mild to moderately severe impairment, be- fering from an ischemic event, treatment will
tween 15 to 25 indicate severe impairment, involve the used of thrombolytic therapy,
and scores >25 indicate very severe neuro- anticoagulants, antiplatelet agents, and neu-
logic impairment.20,21 roprotection. It is important to maintain ade-
The NIHSS score in combination with the quate cerebral perfusion pressure. Even mi-
volume of the ischemia as measured with nor drops in blood pressure could effect the
DWI-MRI, and the time since onset of symp- recovery of the area of ischemic penumbra. It
toms until obtaining the MRI enables the is therefore recommended that the patient’s
identification of patients who have the best blood pressure should not be lowered unless
potential for a good recovery from a stroke it is greater than 185/110 mm Hg and throm-
(see Table 3). Essentially, the smaller the bolytic therapy is being used.3 However, pa-
size of the infarct, the better the potential tients with the following conditions should
of recovery; additionally, those patients with have their blood pressure reduced: acute my-
lower NIHSS scores did better as well. Com- ocardial infarction, hypertensive crises or en-
bining the information from the NIHSS and cephalopathy, renal failure, aortic dissection,
the DWI-MRI resulted in a 7-point score. or retinal hemorrhage. When antihyperten-
Analysis of this scoring system demonstrated sive therapy is begun, blood pressure reduc-
the following: scores of 5 to 7 had the best tion should be done gradually to prevent fur-
outcome, with 87% demonstrating recovery. ther ischemia.3,11,23–25
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
435

TABLE 2
National Institute of Health Stroke Scale

1.a. Level of consciousness: 0: Alert
1: Not alert, but arousable with minimal stimulation
2: Not alert, requires repeated stimulation to attend
3: Coma
1.b. Ask patient the month and their age: 0: Answers both correctly
1: Answers one correctly
2: Both incorrect
1.c. Ask patient to open and close eyes and 0: Obeys both correctly
to grip and release hand 1: Obeys one correctly
2: Both incorrect
2. Best gaze (only horizontal eye movement): 0: Normal
1: Partial gaze palsy
2: Forced deviation
3. Visual field testing: 0: No visual field loss
1: Partial hemianopia
2: Complete hemianopia
3: Bilateral hemianopia (blind including cortical blindness)
4. Facial paresis (ask patient to show teeth or 0: Normal symmetrical movement
raise eyebrows and close eyes tightly): 1: Minor paralysis (flattened nasolabial fold, asymmetry on
smiling)
2: Partial paralysis (total or near total paralysis of lower face)
3: Complete paralysis of one or both sides (absence of facial
movement in the upper and lower face)
5. Motor function—arm (right and left): 0: Normal (extends arms 90 (or 45) degrees for 10 seconds
Right arm without drift)
Left arm 1: Drift
2: Some effort against gravity
3: No effort against gravity
4: No movement
9: Untestable (joint fused or limb amputated)
6. Motor function—leg (right and left): 0: Normal (hold leg 30 degrees position for 5 seconds)
Right leg 1: Drift
Left leg 2: Some effort against gravity
3: No effort against gravity
4: No movement
9: Untestable (joint fused or limb amputated)
7. Limb ataxia: 0: No ataxia
1: Present in one limb
2: Present in two limbs
8. Sensory (use pinprick to test arms, legs, 0: Normal
trunk and face—compare side to side): 1: Mild to moderate decrease in sensation
2: Severe to total sensory loss
9. Best language (describe picture, name 0: No aphasia
items, read sentences) 1: Mild to moderate aphasia
2: Severe aphasia
3: Mute
10. Dysarthria (read several words): 0: Normal articulation
1: Mild to moderate slurring of words
2: Near unintelligible or unable to speak
9: Intubated or other physical barrier
11. Extinction and inattention: 0: Normal
1: Inattention or extinction to bilateral simultaneous stimulation
in one of the sensory modalities
2: Severe hemi-inattention or hemi-inattention to more than
one modality

Reprinted from the National Institute of Health. Available at: http://www.ninds.nih.gov/doctors/index.htm.

436
FRIZZELL AACN Clinical Issues

cious use of t-PA demonstrated improvement

TABLE 3
Three-item Scale for the
of 4 or more points on the NIHSS score.24–26
Prediction of Stroke Recommended criteria for treatment with
Recovery t-PA includes: (1) an ischemic stroke with
a clearly defined time of onset of no more
Factor Assigned Points
than 180 minutes, (2) evidence of neurologic
DWI-MRI volume (mL) deficit measurable on the NIHSS, and (3) a
≤14:1 1 CT scan of the brain with no evidence of in-
>14:1 0 tracranial hemorrhage. Additionally, patients
NIHSS should not be given thrombolytic therapy if
≤3 4
4–15 2
they have had: (1) a stroke or serious head
>15 0 trauma within the past 3 months, (2) have
Time from onset (hours) had major surgery within the past two weeks,
≤3 0 (3) have a prior history of intracranial hem-
3–6 1 orrhage or bleeding from any other body
>6 2 site such as a gastrointestinal hemorrhage,
and (4) have a systolic blood pressure above
Adapted with permission from Baird AE, Dambrosia J, Janket
SJ, Eichbaum Q. A three-item scale for the early prediction 185 mm Hg or diastolic blood pressure above
of stroke recovery. Lancet. 2001;357(9274):2095–2100. 110 mm Hg.27
DWI-MRI, diffusion weighted imaging-magnetic resonance
imaging; NIHSS, National Institutes of Health Stroke Scale.
When appropriate guidelines are followed
for the administration of t-PA, the rate of
hemorrhage as a result of thrombolytic use
Improvement of blood flow to the is- was approximately 5.2% in one study28 and
chemic area of the brain involves the use of 6.5%24 in another. However, for patients who
thrombolytic therapy, which should be ini- did not receive t-PA, the risk of hemorrhage
tiated as soon as possible. However, there after cerebral infarction was 0.6%. The Na-
are several caveats associated with the use of tional Institute of Neurologic Disorders and
this therapy, the most serious being the risk Stroke has identified these factors related to
of hemorrhage. Therefore, recombinant t-PA an increase risk of hemorrhage following the
is the preferred treatment for acute ischemic administration of t-PA: over the age of 70,
stroke.3,23 NIHSS score of more than 20 points, blood
It is extremely important to identify the glucose levels greater than 300 mg/dL, and
patients who will benefit most from the ad- evidence of cerebral edema on CT scan. The
ministration of t-PA. Certain types of stroke, risk of hemorrhage was greater in those pa-
such as lacunar infarcts, have not shown tients who had more than one risk factor.24
any major improvement in outcome with the There have been studies that have ex-
use of t-PA. Therefore, diagnostic imaging amined intracranial administration of throm-
needs to be reviewed to identify the presence bolytics. Although these studies demon-
of ischemic tissue that could be reperfused strated reversal of ischemia with less systemic
through thrombolysis.18 bleeding, this method is not yet approved by
The risk of hemorrhage following the the Food and Drug Administration for use in
use of thrombolytic agents increases with the United States.3
larger strokes, higher doses of medication, Other agents that are used in the treatment
and longer time intervals from the onset of of stroke include antiplatelet therapy and the
symptoms.3 Since timing is an important is- use of anticoagulants. Aspirin used within
sue, it is recommended that the thrombolytic 48 hours of onset of symptoms have been
agent be administered within 180 minutes of shown to reduce risk and mortality. The use
the onset of symptoms. Prompt administra- of the anticoagulant heparin is also beneficial
tion of thrombolytic agents decreases the risk in preventing further clot formation. Current
of disability following stroke by as much as research is being done to develop neuropro-
30%. The patients with the most improve- tective agents that would block amino acid
ment were younger, had smaller ischemic ar- pathways and decrease neurotransmitter ac-
eas and lower NIHSS scores. Overall, judi- tivity of injured tissue.3
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
437

Cerebral Hemorrhagic is a much greater risk of having a stroke

in smokers, with the risk increasing with
Most cerebral hemorrhages develop rapidly
the number of cigarettes smoked per day.7
over 30 to 90 minutes, often with rapid
Patients can also find further information
loss of consciousness. Therefore, it is im-
from the following organizations’ Web sites:
perative to maintain a patent airway. Ini-
(1) National Instituted of Neurological Dis-
tial treatment includes intubation, hyperven-
orders and Stroke at: http://www.ninds.nih.
tilation, elevation of the head of the bed,
gov/, (2) National Institute of Health
and administration of intravenous mannitol
Stroke Scale at: http://www.ninds.nih.gov/
to prevent and reduce elevated intracranial
doctors/index.htm, (3) American Stroke As-
pressure.3
sociation: A Division of American Heart Asso-
Other than reversal of pre-existing antico-
ciation at: http://www.strokeassociation.org,
agulation, nothing can be done to stop the
and (4) National Stroke Association at:
hemorrhage once it begins. If ICP is elevated,
http://www.stroke.org.
osmotic agents and hyperventilation are used
Medications may be needed to control
to reduce it. Cerebral spinal fluid can also be
blood pressure. Adequate control of blood
removed from the ventricles in an attempt to
pressure has been shown to reduce the risk
lower ICP.3
of stroke in older adults. The use of ACE
Patients who survive a cerebral hemor-
inhibitors appears to be helpful in prevent-
rhage have the potential for good recovery.
ing strokes, possibly through the reduction
However, the prognosis is dependent upon
of C reactive protein levels. Treatment goals
the size of the hemorrhage. A hemorrhage
should include maintaining blood pressure
volume <30 mL may have a good progno-
<130/80 mm Hg.3,14,25 Additional research is
sis, whereas a volume >60 mL has a much
also examining the use of angiotensin re-
poorer prognosis.3
ceptor blocking agents, such as losartan, for
Recovery Phase
stroke prevention.29
Elevated cholesterol levels are a risk fac-
Blood pressure levels usually stabilize dur- tor for the development of atherosclerosis
ing the first 2 weeks following a stroke. For and can be viewed as a risk factor for is-
many patients, their blood pressure is lower chemic stroke. Elevated high-density lipopro-
and then gradually increases. Any patient tein (HDL) levels and lower total cholesterol
with persistent elevation in blood pressure (TC) HDL ratios have been associated with
should be evaluated for end-organ damage.25 a decreased incidence of stroke. However,
Patients whose blood pressure is controlled for many people, diet and exercise do not
with angiotensin-converting enzyme (ACE) sufficiently lower the TC-HDL ratio. There-
inhibitors have done better than those treated fore, the use of 3-hydroxy-3-methylglutaryl-
with other antihypertensive medications.14 coenzyme A (HMG-C0-2A) reductase in-
hibitors, such as pravastatin, is recommended
to reduce the risk of ischemic stroke.30
 Prevention Medical therapy also includes the use of
antiplatelet agents. The most frequently used
Prevention of a stroke involves lifestyle agents are aspirin, clopidogrel, and the com-
changes as well as medication and surgery. bination of aspirin plus dipyridamole. The
It is important to review the risk factors with use of antiplatelet agents is currently pre-
patients to be able to identify areas that need ferred rather than using anticoagulants such
to be addressed. Additionally, it is hoped that as warfarin. For patient with atrial fibrillation,
by discussing these issues with patients, they warfarin is preferred. However, the Inter-
will be more likely to comply with the thera- national Normalized Ratio measurement for
peutic regimen. Both diet and exercise can anticoagulant action should be maintained
be used to help control both blood pres- at 2.0 or greater for the best effect. Sur-
sure and cholesterol levels. Smoking cessa- gical intervention with endarterectomy can
tion and reduction of alcohol intake also improve circulation in patients with carotid
must be part of lifestyle modifications. There stenosis.3,24,31
438
FRIZZELL AACN Clinical Issues

 Future Directions for Stroke Care for research. Anti-excitatory agents can be
and Research developed with the goal of blocking of glu-
tamate activity,1 although it was postulated
Just as designated trauma centers have im- that the administration of magnesium, since
proved treatment and outcome for patients it normally blocks the glutamate receptor,
involved in major trauma, the hope for the would provide neuroprotective effects. Early
future is the development of specific stroke studies have only demonstrated a reduction
centers. Since not all hospitals are equipped in patient blood pressure.35 However, more
with advanced radiological imaging meth- research still needs to be done on neuropro-
ods such as DWI-MRI, transport of patients tective agents. Most of the studies36,37 exam-
to hospitals that do have them can aid in ining the role of neuroprotective agents have
rapid diagnosis and early intervention and not used them in combination with throm-
treatment. Thus, the National Institute of bolytic therapy to examine their effectiveness
Neurological Disorders and Stroke is devel- with concurrent effective reperfusion.
oping guidelines for the establishment of Additional suggested research would ex-
designated stroke centers.32 amine the role of other imaging techniques
In addition to the development of stroke such as perfusion-weighted MRI (PWI) in
centers, The National Institute of Neurologi- providing information about the status of mi-
cal Disorders and Stroke is identifying new crovascular perfusion and in the clinical set-
avenues of research for stroke prevention ting is an index of cerebral blood flow. This
and treatment. Specific areas of interest in- would enable the identification of patients
clude defining the biology of stroke through who will derive greatest benefit with the least
the examination of genetic factors, inflam- risk from t-PA.33,37
matory mediators, and the process of stroke Currently research is being done examin-
recovery.32,33 ing the use of endovascular photoacoustic re-
Genetic research can be a valuable part canalization. This new technology uses laser
of the biology of stroke research. There are technology for mechanical clot fragmenta-
genetic responses involved in cellular adap- tion. The goal of this therapy is to rapidly
tation to injury in ischemic events. Further open cerebral vessels and reduce the use of
research into their role can provide addi- thrombolytjcs.38
tional insight into mechanisms of neuronal New treatment options also need to be
survival during hypoxia and ischemia. This explored. This includes direct intra-arterial
could be used to minimize the negative ef- injection of thrombolytic agents, use of de-
fects of ischemia.6,33 fibrinogenating agents such as ancrod, and
Since the inflammatory response plays an carotid artery stenting. Additionally, work is
integral role in the stroke injury, further re- being done to determine of ultrasound tech-
search should examine the relationship be- nology can be used to enhance clot lyses in
tween BP levels, inflammatory mediators, combination with thrombolytic agents.3,33,37,39
and C reactive protein levels. Initial studies of
patients taking ACE inhibitors have demon-
strated that levels of C reactive protein levels  Conclusion
are reduced.14 Thus, further study could de-
termine if there are neuroprotective effects Cerebrovascular disease and its sequelae are
from the action of ACE inhibitors.14 a significant cause of morbidity and mor-
Agents such as abciximab (ReoPro), an an- tality among older adults. Although lifestyle
tiplatelet agent that exerts its effects through modifications can reduce the risk of develop-
the glycoprotein IIb/IIIa receptor, are being ing a stroke, for many individuals, medica-
studied. It is hoped that administering them tions are part of their risk reduction regimen.
during the first 6 hours following the onset of Once a stroke has occurred, there needs to
symptoms will also be beneficial. Current re- be rapid identification of the type and extent
search is examining their role either alone or of the event so that immediate and appropri-
in conjunction with thrombolytic therapy.34 ate treatment can be initiated. Future designa-
The role of neuroprotective agents in the tion of specific stroke centers would be a sig-
treatment of stroke is also an important area nificant step in improving patient outcome.
Vol. 16, No. 4, Oct-Dec 2005 ACUTE STROKE
439

However, much research still needs to be 13. Falcao ALE, Ruetens DC, Maarkus R, Koga
done to promote the best level of neurologi- M, Read SJ, Tochon-Danguy H, Sachinidis J,
cal recovery following a stroke. Howells DW, Donnan GA. The resistance of
ishemia of white and gray matter after stroke.
Ann Neurol. 2004;56:695–701.
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