You are on page 1of 12

Vol. 102 No.

2 August 2006

ORAL MEDICINE Editor: Martin S. Greenberg

Stroke: epidemiology, classification, risk factors, complications, diagnosis,

prevention, and medical and dental management
Mahnaz Fatahzadeh, DMD,a and Michael Glick, DMD,b Newark, NJ

Cerebrovascular accident, or stroke, refers to an acute onset of neurologic deficits lasting more than 24 hours or
culminating in death caused by a sudden impairment of cerebral circulation. Stroke is the third leading cause of death and
a major cause of long-term disability in the United States. This article provides the dental community with an up-to-date
understanding of the epidemiology, classification, risk factors, complications, diagnosis, prevention, and medical and dental
management issues pertaining to stroke. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:180-91)

Cerebrovascular accident (CVA), stroke, or brain PATHOGENESIS AND CLASSIFICATION

attack refers to an acute onset of neurologic deficit The underlying pathogenic mechanism for cerebro-
lasting more than 24 hours or culminating in death vascular accidents is the interruption of blood flow
caused by a sudden impairment of cerebral circulation.1 and delivery of essential oxygen and glucose to the brain
Stroke is the third leading cause of death in the United tissue. The brain does not store glycogen and requires
States, Europe, and most countries in the world.1-4 In 60-70 mL of perfusion per 100 g of tissue per minute
2005, nearly 700,000 strokes and 160,000 stroke-related for normal function.14 A drop in the blood flow to
deaths will occur in the United States,5,6 which com- 25 mL/100 g/min leads to neuronal ischemia, energy
putes to 1 stroke every minute.7 In addition, magnetic failure, and neurologic symptoms, followed by irrever-
resonance imaging (MRI) studies reveal that nearly sible tissue damage within minutes should ischemia
22 million asymptomatic strokes occur every year.8 continue.11,14,15
Stroke is also a major cause of prolonged neurologic Four neurologic phenomena have been defined for
disability in adults,2,3,5,7,9 with an annual economic stroke based on their duration: transient ischemic at-
burden of nearly $45 billion in the United States.10,11 tacks (TIAs), reversible ischemic neurologic defect
Incidences of stroke-related deaths and disability are ex- (RIND), stroke in evolution, and completed stroke. A
pected to rise even higher as the population ages.1,3,4,11-13 TIA is a sudden, short-lasting, focal neurologic deficit
In fact, extrapolation of the current data predicts that or mini stroke caused by transient and localized brain
the mortality rate from stroke will double by 2020,1 ischemia.11 These neurologic deficits are reversible
which highlights the significance of stroke-prevention within 24 hours11 but often signal an impending stroke
measures.3 The preceding discussion reviews relevant within days.7,16 RIND refers to a neurologic impairment
topics with regard to the stroke focusing on the medical that is reversible but recovery from which will exceed
and dental management issues of concern to dental 24 hours.16 A stroke in evolution is defined as stroke-
practitioners. associated symptoms that progressively worsen over
time.11,16 In contrast, neurologic signs and symptoms
that have been stable for more than 24 hours define a
Assistant Professor, Division of Oral Medicine. completed stroke.11
Professor and Chairman. Strokes are subclassified into ischemic and hemor-
Received for publication Dec 8, 2004; returned for revision Jul 15, rhagic types, based on the underlying pathogenesis.11
2005; accepted for publication Jul 29, 2005.
1079-2104/$ - see front matter
Eighty-five percent of strokes are ischemic in nature
2006 Mosby, Inc. All rights reserved. and involve the occlusion of a cerebral vessel with sub-
doi:10.1016/j.tripleo.2005.07.031 sequent brain ischemia and infarction distal to the site of

Volume 102, Number 2 Fatahzadeh and Glick 181

obstruction, which may be caused by either atherscler- of collateral circulation, blood pressure (BP), and body
otic thrombi or distant emboli.11,14,17 temperature are factors that affect the final dimension of
Embolic strokes are classified into arterial, cardioem- brain infarct.11,18 Clinical manifestations of stroke vary,
bolic, and cryptogenic subtypes, depending on the site depending on the site and size of the brain lesion.9,11
of embolic origin.11 Common sources of cerebral embo- Signs and symptoms of stroke are numerous and may
lism include atherothrombi in the carotid bifurcation or include variable sensorimotor dysfunctions, such as
aortic arch, cardiac disease, and spontaneous thrombo- hemiplegia, hemiparesis, hypoesthesia, compromised
sis in hypercoagulable conditions.11,17 Multiple septic eye movements, visual defects, deafness, and language
cerebral emboli may also arise from valvular vegeta- problems, as well as memory disturbance, headache, al-
tions in bacterial endocarditis.11,17 Diagnosing the exact tered mental status, dizziness, nausea, and vomiting.9,11
source of embolism may be challenging, but this in- Of these, progressive neurologic impairment, early
formation is critical for reduction of stroke-related changes in mental status, abrupt headaches, seizures,
deaths.11 Cryptogenic strokes refer to cerebrovascular and vomiting are more common, and focal neurologic
events in which the source of occlusive emboli remains deficits typical of ischemia are less frequent, with hem-
unknown.11 orrhagic strokes.9,11
Differentiation of ischemic stroke subtypes is not
clinically possible, although certain features may help DIAGNOSIS AND LABORATORY TESTING
in diagnosis.14 In general, the neurologic symptoms of Application of effective preventive and therapeutic
thrombotic stroke develop slowly, whereas sudden, mul- interventions requires a precise knowledge of underly-
tifocal, and maximal neurologic deficits at the onset ing stroke mechanism.14 Many other conditions can
often indicate an embolic stroke.11,17 In addition, early resemble the features of stroke and confound the
seizures and hemorrhagic transformation are more diagnostic process. Focal neurologic deficits are not
frequent with embolic events.11,17 unique to stroke and may also occur in the context of
Three main types of ischemic stroke syndromes an epileptic seizure attack or an acute hypoglycemic
have been described. A lacunar stroke results from the episode.9 In addition, brain neoplasms, acute sepsis,
obstruction of the small penetrating arterioles that infectious encephalitis, multiple sclerosis, prolonged
feed the white matter structures and the thalamus.11,14 migraneous aura, and severe metabolic imbalances
Symptoms of small-vessel stroke are often transient, may occasionally mimic the signs and symptoms of
sparing high-level brain functions.14 Predisposing fac- stroke.9 The precise etiology of an ischemic stroke
tors for lacunar strokes include aging and uncontrolled may remain unknown in many cases, even after ex-
hypertension.11 In contrast, large-vessel stroke is char- tensive diagnostic work ups.9 The incidence rate for
acterized by extensive cerebral infarction and results ischemic strokes of unknown etiology has been reported
from thrombotic occlusion of a major intracranial ves- to be in the range of 18% to 40%.19,20
sel.14 Frequently, high-level brain functions are affected A number of diagnostic modalities can be used to
and prognosis is poor.14 Brainstem stroke, the third is- exclude conditions with signs and symptoms sugges-
chemic stroke syndrome, may result from the occlusion tive of stroke. Factors critical to the diagnostic process
of either small or large cerebral vessels and has a varia- include patient age, medical history, clinical presentation,
ble clinical presentation.14 the temporal profile of the event, location of the infarct,
Fifteen percent of all strokes are hemorrhagic in stroke subtype, and specific etiology.9 Clinical examina-
nature.11,14 Hemorrhagic brain infarction may result tion should be thorough and focused on the heart, ret-
either from displacement of cerebral tissues or from inas, and peripheral vascular system.11 Vascular testing
toxic effects of extravasated blood.11,18 Whereas two- such as cerebral angiography or Doppler ultrasonogra-
thirds of hemorrhagic strokes are caused by intracerebral phy will often shed light on the nature, location, and
bleeding, the remaining one-third may be attributed to severity of vascular lesions in significant vessels of the
aneurysmal rupture and subarachnoid hemorrhage.14 head and neck.4 Cardiac auscultation, echocardiography
Predisposing risk factors for intracranial hemorrhage and electrocardiography can be used to disclose valvular
include hypertensive encephalopathy, advanced age, or rhythm abnormalities, conduction problems, and a
hematologic disorders, head injury, strenuous exercise, recent myocardial infarction (MI).11,17
and abuse of alcohol or illicit drugs.11 Indicated laboratory tests include complete blood
count, chemistry, serum electrolytes, urinalysis, erythro-
CLINICAL MANIFESTATIONS cyte sedimentation rate, screening for hypercoagulability,
Irrespective of the etiology, brain edema is the first in serologic tests for syphilis, blood sugar, cholesterol, and
the post-stroke cascade of events.1 The site, size, and du- lipid levels.4,11 Lumbar puncture may assist in the ex-
ration of occlusion or hemorrhage, presence or absence clusion of subarachnoid hemorrhage or meningitis as
182 Fatahzadeh and Glick August 2006

the underlying cause.11 Blood cultures and echocardiog- as a healthier diet, greater physical activity, smoking
raphy are indicated if septic emboli secondary to infec- cessation, moderating intake of alcohol, and stress re-
tive endocarditis is suspected.17 duction are the core requirements for primary stroke
History and clinical examination cannot reliably prevention.7,32 Screening for comorbidities such as
rule out hemorrhagic stroke, a distinction necessary be- hypertension (HTN), MI, atrial fibrillation (AF), con-
fore emergency management can begin.9,11 Diagnostic gestive heart failure (CHF), diabetes mellitus, carotid
imaging with computerized tomography (CT) or MRI artery stenosis (CAS), and hypercholesterolemia is
is always indicated to identify the presence, nature, also an effective primary prevention strategy.3,7,35
and extent of brain injury, particularly if thrombolytic In contrast to the primary prevention of MI, the role of
intervention is being considered.4,11 A noncontrast antiplatelet drugs, including aspirin, in the prevention of
head CT is the traditional diagnostic imaging technique a first stroke is controversial.3,32 Nevertheless, adminis-
when clinical signs and symptoms are suggestive of tration of antiplatelet or anticoagulation agents are po-
acute stroke,1,21 although advanced MRI techniques tential strategies for the prevention of cardioembolic
are fast becoming the imaging modality of choice in stroke in those with AF.3,11,17,18,32,36 Prophylactic anti-
these situations.22,23 Recent work indicate that T2- coagulation is also indicated for patients with MI,
weighed MRI is more reliable than CT in the diagnosis mechanical heart valves, and CHF who are at risk for
of intracerebral and subarachnoid hemorrhages.24-26 In thromboembolism.17,37 Routine anticoagulation, how-
addition, diffusion-weighted MRI allows for distinction ever, is not warranted for patients with bioprosthetic
of ischemic from hemorrhagic infarcts faster and better valves in the absence of previous thromboemolism.17
than CT.27,28 Therefore, CT is no longer necessary for The annual incidence of intracranial hemorrhage, the
diagnosis of acute stroke if modern MRI is accessible.24 main adverse effect of anticoagulant therapy, is about
Irrespective of the imaging technique selected, 1%.17,38 A history of ischemic stroke, intensive antico-
knowing the date and time of stroke onset is critical to agulation, HTN, and older age increase the risk of this
proper interpretation of the imaging.1 The gold standard complication, highlighting the importance of patient
for visualization of cerebrovascular anatomy is cerebral selection.17
angiography,21 which is nondiagnostic in many cases of Carotid endarterectomy is a well established preven-
cardiogenic stroke but may identify the sites of vascular tive strategy against cerebrovascular disease.11 Asymp-
stenosis where emboli are potentially trapped.29 Para- tomatic CAS refers to the absence of clinical signs or
doxically, cerebral angiography may precipitate an symptoms of stroke or TIA ipsilateral to the carotid
embolic event.14 Localization of vascular narrowing and obstruction.11 Conversely, CAS on the same side as
detection of cerebral emboli can also be accomplished vascular distribution of a stroke or TIA is defined as
with transcranial doppler ultrosonography.17,21 In addi- symptomatic.11 The preventive approach for patients
tion, brain and vascular imaging may be efficiently with asymptomatic carotid disease remains controver-
obtained by magnetic resonance angiography and sial.3,11,32 In general, aspirin therapy and risk-factor
perfusion CT.24,30 Moreover, transthoracic or transeso- modification are the recommended approaches for
phageal echocardiography can be used to identify poten- patients with asymptomatic carotid disease.11
tial cardiac sources of embolism.31 Stroke recurrence is a significant concern with regard
to an increase in mortality, disability, length of hospital
RISK FACTORS AND PREVENTION stay, and contribution to vascular dementia.39,40 Rates of
Management of the stroke patient starts with pre- recurrence vary depending on the stroke subtypes, with
vention. Strategies to reduce stroke-related death and lacunar and thrombotic strokes having the lowest and
disability significantly impact public health.7,11 Epide- highest recurrence rates, respectively.39 A history of
miologic studies have identified many predisposing fac- TIAs or minor strokes predisposes patients to subse-
tors associated with stroke, and primary prevention quent stroke and up to a third of recurrences occur
focuses on the modification of those risk factors in the within 1 month of the initial event.11,41 Understanding
general population.7 Nonmodifiable risk factors include the underlying mechanism for the first stroke and iden-
advanced age, male gender, nonwhite race, and hereditary tifying modifiable risk factors in the target population
predisposition.3,32 Incidence of stroke increases with are critical to secondary stroke prevention.9 Risk-factor
age.11 Specifically, 75% of all strokes in white people modification has a more direct effect on the prevention
and the majority of ischemic strokes occur in people of the first stroke than on recurrent strokes.3 Neverthe-
over the age of 65.12,33,34 Other risk factors for stroke less, risk-factor modification should be part of a compre-
include inherited or acquired hypercoagulable conditions, hensive stroke-prevention program.3,11 Reduction of BP
oral contraceptive use, stress, and previous cerebrovascu- is a highly effective strategy in the prevention of both
lar events.4,7,11 Initiating life-style modifications such ischemic and hemorrhagic strokes.42,43
Volume 102, Number 2 Fatahzadeh and Glick 183

Oral anticoagulation therapy with warfarin is a well complications, and attempt to minimize stroke
established strategy in the prevention of recurrent ische- recurrence.56
mic stroke in patients with AF and offers a definite In general, stroke victims are most effectively man-
advantage over aspirin therapy.32,44-47 Warfarin therapy aged in stroke centers equipped with advanced technol-
also benefits patients with other potential cardiac sour- ogy and experienced multidisciplinary personnel.4,14
ces of embolism, such as mechanical valve or left ven- Studies have shown a dramatic reduction in mortality,
tricular aneurysm.48 In patients with extensive brain disability, and long-term care needs of patients who
lesions, oral anticoagulants are typically withheld dur- were managed in stroke centers compared to regular hos-
ing the period immediately following an ischemic stroke pital wards.56-58 Immediate poststroke interventions fo-
to reduce the risk of hemorrhagic transformation.48,49 In cus on life support through respiratory and cardiac care,
general, however, the benefits of oral anticoagulation control of BP, monitoring oxygen saturation and blood
with warfarin in secondary stroke prevention outweigh glucose level, prevention of metabolic disturbances,
the risk of hemorrhagic adverse effects.11 maintenance of organ function, and management of ele-
Single or combination antiplatelet agents, such as vated intracranial pressure (ICP).11,48,58 Stroke victims
aspirin, clopidogrel, ticlopidine, or dipyridamole, in a are also closely monitored for signs and symptoms of
variety of doses, constitute the primary strategy for the neurologic deterioration indicative of intracerebral hem-
prevention of recurrent ischemic stroke in patients with- orrhage.59 Tight control of BP, adequate hydration, and
out a cardiogenic source.3,11,32,48 A potential drawback close follow-up is especially important for patients
associated with antiplatelet therapy is breakthrough with hemorrhagic stroke.11 Neurosurgical evaluation
CVA or stroke recurrence while on antiplatelet ther- may also be necessary for those with cerebellar hemor-
apy.1 Individuals taking antiplatelet medications dem- rhage, ischemic cerebellar lesions, and depressed mental
onstrate a wide variability in the inhibitory effect of status.9,11 In addition, the head of the bed should be kept
these agents on platelet aggregation as well as alteration elevated until high ICP is excluded.11
of response with chronic therapy.50 Therefore, failure of Optimal therapeutic outcome in stroke management
antiplatelet therapy in the prevention of recurrence may depends on having a clear understanding of underlying
be caused by patients incomplete response to therapy or mechanisms.14 After the type of stroke has been estab-
development of resistance with prolonged therapy.50,51 lished, efforts center on preserving ischemic brain
In addition, adverse effects such as aspirin-induced gas- tissue, maximizing neuronal survival, and preventing
trointestinal bleeding or ticlopidine-induced agranulo- further thrombosis or hemorrhage.14,48 In contrast to
cytosis are examples where the therapy is not tolerated myocardial salvage of ischemic heart, recanalization
by patients.13 is more challenging in the context of acute ischemic
Patients with greater than 70% CAS and a history of stroke (AIS), perhaps because thromboemboli in the is-
stroke or TIAs are 6 times more at risk of a recurrent chemic stroke are often larger, harder, older, more var-
stroke on the side of the stenosis compared to asymp- iable in their composition, and, consequently, less
tomatic patients.52,53 Significant reduction in the risk responsive to thrombolytic interventions.59 Also, ves-
of recurrent stroke has been reported with surgical inter- sels involved in the stroke are more tortuous, often
vention in patients with greater than 70% CAS, provided transversing through bony cranial foramina, which
the surgical risk is less than 7%.1,11,54,55 can make catheterization mechanically difficult and
time consuming.59 In addition, intracranial hemorrhage
MEDICAL MANAGEMENT is a more common side effect of thrombolytic therapy in
Timely recognition and management of stroke is the very old, who are particularly prone to ischemic
critical for reduction of stroke-related morbidity strokes.60
and mortality.9 The phrase time is brain implies that Dissolution of clots can be attempted with the in-
immediate intervention improves neuronal salvage and travenous (IV) tissue plasminogen activator (t-PA) in
functional recovery.1,4,9,14 Caregivers have a critical appropriately selected patients who have symptoms of
role in the overall management of stroke victims. ischemic stroke less than 3 hours in duration.9,14,61-63
Caregivers are important members of the team and The time of stroke onset is critical to an optimal out-
should be educated about the symptoms of stroke, poten- come for thrombolysis. Stroke onset is defined as the
tial complications, prevention measures, and the abso- time the patients symptoms started or the time the
lute necessity for emergent care if the need arises.9 patient was last seen in the normal state of health.9,11
In the overall management of stroke patients, physicians Even within the 3-hour window period, the earlier that
address the acute and long-term effects of stroke, t-PA is administered the greater is the likelihood of a
consider risks and benefits of medical and rehabilita- successful outcome.64 Studies demonstrate that throm-
tive options, individualize therapy, prevent potential bolytic intervention with IV t-PA is beneficial and cost
184 Fatahzadeh and Glick August 2006

effective for all subtypes of ischemic stroke, because has been efficacious in preventing recurrent stroke,
patients often return home earlier and have less re- death, and disability.1,9,11,77-80
sidual disability.62,65 Recent evidence suggests that It should be emphasized that currently used inclusion
effectiveness of thrombolytic therapy with IV t-PA and exclusion criteria for thrombolytic therapy were
may also depend on the genotype of the patient.66 established by the National Institute of Neurological
Thrombolytic intervention with IV t-PA appears to Disorders and Stroke a decade ago when diagnostic
have a low rate of early recanalization.59 Intra-arterial technology was much less sophisticated.26,75 Even
administration of t-PA, urokinase, and prourokinase though guidelines emphasize a time frame of less than
have been attempted to achieve faster and more effec- 3 hours duration for treatment, other studies have shown
tive thrombolysis and neurologic recovery.59,67-68 This potential benefit from both IV and intra-arterial throm-
approach appears to shorten the time from onset of bolysis initiated more than 3 hours after the onset of
symptoms to arterial recanalization and to achieve a stroke symptoms.68,81
higher rate of recanalization, posing the same level The role of anticoagulation in the emergency man-
of risk for intracerebral hemorrhage reported for IV agement of AIS is uncertain.9,11 Emergent full-dose an-
t-PA.59 Studies have shown a correlation between initi- ticoagulation therapy with heparin was commonly used
ating intra-arterial thrombolysis within 3 to 4 hours of early after the onset of mild ischemic stroke to prevent
symptom onset and higher rates of early recanalization its progression.11,82-84 Heparin administration often
and more favorable therapeutic outcomes.69-70 was continued for a few days before substitution with
Intravenous streptokinase and viprinex, a fibrinolytic long-term warfarin or antiplatelet drugs.11 However,
agent derived from the venom of the Malaysian pit vi- recent studies have revealed no benefit for using early,
per, have been tested in a number of thrombolytic trials full-dose, subcutaneous, low-molecular-weight heparin
but with little success.59,71-72 Of the agents described, over aspirin alone in patients with AF who had suffered
only IV t-PA is approved for thrombolytic therapy in ischemic strokes.34,84 Potential indications for early
the United States.14,59,71 A frequent and serious adverse heparin administration after AIS may include transient
event associated with thrombolysis is intracerebral ischemic attacks in patients with severe CAS or AF
hemorrhage, which necessitates a thorough risk-benefit who are scheduled to receive surgical endarterectomy
analysis and careful patient selection.59,73 If thrombo- or oral anticoagulation therapy, respectively.48
lytic therapy is selected, BP should be closely moni- Multifaceted interventional strategies aimed at
tored and the use of heparin or aspirin should be improving recanalization include administration of
avoided during the first 24 hours.9,74 combined IV and intra-arterial t-PA, angioplasty, and
Exclusion criteria for thrombolysis have been speci- mechanical disruption of the clot using special catheters,
fied in the literature.9,59,74 They include late thrombo- laser, or ultrasound energy.60,85-87 Intra-arterial third-
lytic intervention beyond three hours window period, generation recombinant t-PA and abciximab, a GIIb/
current oral anticoagulation or heparinization within IIIa receptor blocker, as well as their combination, are
48 hours with respectively high PTT and INR, thrombo- examples of newer agents currently under investigation
cytopenia with platelet count of less than 100,000/mm3, for IV administration in patients with AIS.88-89
consistently high pre-treatmet BP readings (systolic A potential sequela of stroke is loss of cerebral auto-
[185 mm Hg or diastolic[110 mm Hg), previous intra- regulation and a subsequent drop in the perfusion
cerebral bleeding, recent major surgical procedure, on- pressure.9,11,14 Although management of poststroke BP
set of seizures simultaneous with stroke symptoms, depends on the stroke etiology,9,14 dehydration and hypo-
rapid resolution of neurological impairment and other tension may exacerbate the infarction and should be pre-
contraindications.9,59,74 vented.9,11,14 Cerebral nutritive perfusion and neuronal
Currently, less than 5% of patients with AIS receive salvage may be improved by the restoration of blood
thrombolytic therapy with IV t-PA.75-76 Failure to treat flow through thrombolysis and increasing collateral cir-
is most often due to the stringent criteria for thrombo- culation to the ischemic regions.14 In addition, supple-
lytic intervention and patient arrival beyond the 3-hour mental oxygen and hyperventilation may be indicated
window period.62,76 Initiating intra-arterial thromboly- for hypoxic patients.9 Cerebral perfusion is also influ-
sis within 6 hours of the ischemic stroke onset may be enced by gravity, which is demonstrated by the exacerba-
attempted for patients who do not meet the criteria for tion of neurologic impairments upon standing and clinical
IV thrombolysisif skilled personnel and equipment improvement when the stroke victim is supine.14,90 For
are available.14 Alternatively, these patients may receive optimal outcome, victims of ischemic stroke should be
oral aspirin (160-325 mg) soon after the stroke in the placed in a horizontal position if ICP is normal.91
absence of contraindications.1,9,77-78 Administration of Antibiotics, antipyretics, and insulin should be used in
aspirin within the first 48 hours of an ischemic stroke the management of infection, fever, and hyperglycemia,
Volume 102, Number 2 Fatahzadeh and Glick 185

respectively.9 Hyperglycemia-induced lactic acidosis pneumonia should be acknowledged and early patient
may exacerbate cerebral infarction, which emphasizes mobilization encouraged.14
the importance of poststroke normoglycemia.92 Fever Poststroke sleep-disordered breathing and hypersom-
negatively impacts stroke outcome, whereas hypother- nia are serious complications of stroke.98 Hypersomnia
mia improves neuronal salvage.93-94 often interferes with neurologic recovery and the reha-
Neuroprotection refers to therapeutic modalities that bilitation process, exacerbates memory and cognitive
improve cerebral tissue tolerance to oxygen deprivation impairment, and reduces the stroke patients overall
while definitive measures are taken to curtail ischemic quality of life.98-100 Chronic episodic hypoxia and hy-
insult.11 The most effective neuroprotective measure percapnia secondary to sleep apnea could also lead to
is applied hypothermia within 2 hours of stroke onset serious sequelae such as pulmonary hypertension and
accompanied by other efforts to correct brain ische- cor pulmonale.98 Stroke-related central and obstructive
mia.11,48 Despite positive outcomes in animal studies, sleep apnea may improve with discontinuation of seda-
no neuroprotective agents are currently approved for tive medications and administration of continuous pos-
clinical use.11,95 Other potential neuroprotective agents itive airway pressure.98 In addition, administration of
currently under study include blockers of excitatory a central nervous system stimulant often improves
amino acid pathways, free-radical scavengers, and cyto- stroke patients attention to rehabilitative efforts.98
kine inhibitors.9,11,71 Prolonged bed rest can lead to neurovascular decondi-
tioning,98 which refers to harmful physiologic changes
such as reduced cardiac performance and diminished
COMPLICATIONS postural reflexes that can predispose stroke victims to
The prevention and management of poststroke com- cardiac events and orthostasis. Neurovascular decondi-
plications is critical to overall care of stroke patients. tioning may be improved by exercising in the supine
Neurologic complications include intracranial bleeding, position, sitting in a chair several hours at a time, and
edema, and poststroke seizures.48 Secondary infections, performing isometric exercises.98 Periodic arm eleva-
deep vein thrombosis (DVT), pulmonary embolism, as- tion, motion exercises, corticosteroid injections, or tak-
piration pneumonia, and decubitus ulcers are potential ing analgesics may help relieve hemiplegic shoulder
medical complications.48 Increased ICP secondary to pain, a frequent complication of stroke.98 Poststroke
brain edema or hematoma is a serious stroke-related spasticity may also be reduced by medications, stretch-
sequela.9 Ischemic brain edema develops within the ing exercises, and positioning devices.98
initial 24 to 48 hours after stroke and may clinically Urinary tract infections and constipation are frequent
manifest with altered mental status, asymmetrical pu- poststroke complaints, often manageable by discontinu-
pils, cranial nerve paralysis, papilledema, and episodic ing indwelling catheters and encouraging ambulation to
breathing.9,48 Elevated ICP is often fatal in young stroke assist with intestinal motility.9,14
victims because of potential cerebral herniation.96 Nearly 20% of stroke victims with left-sided brain
Management approaches for ischemic brain edema in- injury have difficulty with speech, comprehension,
clude raising the head of the bed, administering osmotic reading, and writing.101,102 Temporary or permanent
diuretics, restricting fluids, hyperventilation, hypother- debilitation in vision, communication, mentation, or
mia, and decompression surgery to preserve and in- motor function greatly impacts the stroke survivors
crease cerebral perfusion.9,11,48 independence and psychological well-being.4,103 Unex-
Ten percent of stroke victims may experience sei- pected physical disability, communication impairment,
zures, most often in the context of hemorrhagic stroke and poor self-perception may foster denial, hopeless-
or extensive cortical lesions.9 Anticonvulsants can be ness, anxiety, and anger before a stroke patient learns
used to control poststroke seizures. Nonambulatory to accept the new limitations.101
stroke victims are at risk for DVT.97 Low-dose IVor sub- Poststroke depression is reported in 50% of stroke
cutaneous heparin or heparinoid compounds, external victims and appears to be linked with higher mortal-
compression stockings, and early ambulation are effec- ity.101,104 Manifestations of poststroke depression,
tive strategies for DVT prophylaxis.9,48,83,97 In addition, such as depressed mood, anxiety, irritability, poor sleep,
bronchiolar atelectasis secondary to prolonged bed lack of drive, social withdrawal, and loss of appetite,
rest, together with the patients inability to protect his are frequently compounded by a stroke patients com-
or her airway while feeding, frequently predispose munication deficit.98,101,105-106 Timely recognition and
stroke victims to aspiration pneumonia.14 Oral feeding treatment of poststroke depression positively impacts
should be withheld until the stroke victim has been survival, functional rehabilitation, quality of life, and
evaluated and deemed to be capable of normal swallow- the overall cost of care.105 Cognitive functions are
ing.9 Moreover, the possibility of silent aspiration frequently intact in poststroke victims; however,
186 Fatahzadeh and Glick August 2006

intellectual deficits have been reported with extensive result in pocketing of food and neglect of oral hygiene
left-sided brain infarcts.107 Vascular dementia or the cu- on the affected side, both of which predispose patients
mulative effect of multiple cerebral infarctions on the to caries, periodontal disease, and halitosis.101,114 The
progressive impairment of intellectual capacity account caries susceptibility is further exacerbated by the xero-
for 5%-20% of cases of cognitive impairment.40,108 stomia-inducing medications used in the management
Poststroke sexual difficulties secondary to left hemi- of stroke and its sequelae.101,118
spheric lesions, loss of drive, depression, concern about Certain medications used in the management of
relapse, or even embarrassment with intimacy have been stroke interfere with hemostasis.114,118 In addition,
reported in the literature.109,110 An integral part of a disability and neurologic deficits affecting hearing,
comprehensive rehabilitation protocol is the evaluation vision, speech, and memory frequently lead to difficulty
of poststroke sexual difficulties in an attempt to over- with communication and follow-up with dental instruc-
come any psychologic barriers and improve the stroke tions.101,114 Poststroke depression and lack of motiva-
patients quality of life.110 tion often result in failure of patients to keep their
appointments, appreciate treatment objectives, or com-
PROGNOSIS ply with recommendations.101
The size and location of the brain lesion determine Some studies suggest a possible association between
stroke outcomes, such as death and disability. The chronic inflammatory periodontal disease and the inci-
most significant sequela of stroke is death and nearly dence of cerebrovascular events119-121 Although the
one-third of stroke victims die within 1 year of the precise mechanisms of this interaction are not fully un-
event.1 Important predictors of stroke recurrence and derstood, periodontal pathogens and systemic immu-
mortality within 3 years of the initial event include prior noinflammatory processes have been implicated in the
history of TIAs, AF, coronary heart disease, and disabil- initiation or progression of atherosclerosis and ulti-
ity at discharge.111 The pathologic type of stroke, as well mately susceptibility to stroke.119-121 Though advocated
as the subtype of ischemic stroke, influence stroke- by some investigators, the contribution of prevention or
related mortality.1,16 The reported mortality rates for aggressive treatment of periodontal infections to reduc-
strokes caused by intracerebral hemorrhage, subarach- tion in the risk of stroke remains controversial.122
noid hemorrhage, and thrombotic vascular blockage
are 80%, 50%, and 30%, respectively.16 In addition, DENTAL MANAGEMENT
the poorest survival rate is reported for the cardioem- In general, a standard evidence-based protocol for
bolic subtype of ischemic stroke.33 More than half of dental management of stroke patients is not available,
stroke survivors are afflicted with significant temporary and current recommendations are based primarily on
or permanent neurologic impairment.1,112 Although intuitive extrapolations from the medical literature.
stroke-related deficits may improve over time, recovery Major issues to be considered when treating patients
depends on the nature and extent of the initial deficit and at risk for or after a stroke include screening for risk
is not always predictable.113 A significant long-range factors, hemostasis, drug actions and interactions,
goal in medical management involves physical, occupa- stress induced by the dental care, empathetic approach
tional, and speech rehabilitation of the stroke victims. by the dental staff, and individualized oral care
ORAL IMPLICATIONS Dentists see their patients regularly and are in a key
The oral manifestations of stroke include loss of position to contribute to stroke prevention through iden-
sensation of oral tissues and unilateral paralysis of oro- tification of susceptible patients and education aimed at
facial structures.11,101,114 Impaired movement of oral modification of risk factors, as well as medical referral
structures may manifest as inability to manage oral for further evaluation. Calcified atherosclerotic lesions
secretions, maintain a protective gag reflex, articulate at the common carotid bifurcation are occasionally
speech, expectorate, or reproduce a jaw posture neces- detected on panoramic dental radiographs in neurologi-
sary for a functional occlusion.101,102,115 More than 50% cally asymptomatic patients.123,124 Some investigators
of stroke patients suffer from dysphagia, often having have suggested that these calcifications are markers of
more difficulties managing liquids than solids.101,116 advanced extracranial carotid disease and subsequent
Poststroke swallowing impairment may manifest as risk for ischemic cerebrovascular events.123-127 Al-
tongue hypermobility, coughing, and choking.101 though the significance of carotid calcified atheromas
Dysphagia-related changes in mastication and dietary visible on panoramic radiographs is controversial, den-
habits can potentially lead to poor nutrition, weight loss, tal professionals should understand the epidemiology
and subsequent problems such as poor fit of oral appli- and pathogenesis of carotid calcifications, differentiate
ances101,117,118 Oral sensorimotor impairment may them from other potential anatomical and pathological
Volume 102, Number 2 Fatahzadeh and Glick 187

radiopacities in the region of the carotid artery, and refer opioids, and related analgesics may be considered as
patients for follow-up as needed.123,124 suitable substitutes.137,139,140 Potential interactions be-
Dental professionals should also be able to recognize tween prescribed dental medications and oral anticoag-
signs and symptoms of stroke and appropriately manage ulants are also a concern. For instance, metronidazole
an emergency in the dental office. In general, mainte- and erythromycin as well as tetracycline may increase
nance of patient in the supine position, administration INR by inhibiting metabolism of coumadin as well as re-
of oxygen, monitoring of vital signs, activation of emer- ducing prothrombin activity, respectively.141-144 These
gency medical support, and prompt transportation to an interactions require the clinician to avoid concurrent
emergency facility are essential for timely and effective administration of metronidazole or erythromycin with
medical interventions. In addition, dental professionals oral anticoagulants and closely monitor INR when the
should accurately describe the patients signs and symp- patient is taking both coumadin and tetracycline.141
toms and the precise time of onset to the emergency Alleviation of stress before and during dental treat-
personnel. ment may be accomplished by N2O-O2 inhalation seda-
The initial evaluation of the dental patient with a his- tion and/or premedication with oral anxiolytics as well
tory of cerebrovascular disease should include deter- as profound anesthesia and short dental appoint-
mination of the specific diagnosis, date of the event, ments.145 Pre- and intraoperative vital signs should
current status, medical management, and any residual also be monitored and recorded. In addition, the use of
disability.101 The risk of recurrent stroke in a patient rubber dam, effective oral evacuation, and facilitative
with a history of stroke or TIAs is greater than the risk head positioning alleviate patients fear of choking
of the first stroke in a person with no prior cerebrovascular and reduce the risk of aspiration.101 Though many
event.11,16,128 The risk of recurrence is highest soon after stroke victims are adequately managed in an outpatient
the initial event, but it may remain elevated for several environment, some may require airway protection
years.129 The presence of TIAs before or after an acute through intubation in the operating room.
stroke predicts early recurrence within the first 90 Dental staff should demonstrate an empathetic and
days,130 and up to 30% of ischemic recurrences are re- supportive approach in understanding the patients
ported to occur within 1 month of the first stroke.41,128,131 physical and emotional limitations and allocate extra
Extrapolating from this type of data, some authors recom- time for communication and clinical procedures.102,114
mend a cautious approach by deferring the elective dental Hemiplegic stroke victims may require assistance
care for the first 6 months following a stroke and in pa- while walking or transfering to and from the dental
tients experiencing TIAs or RINDs.114 chair.101,114 Oral hygiene aids and instructions should
Therapeutic administration of single/combination be individualized based on the patients ability to per-
antiplatelet agents or subcutaneous low molecular form effective oral care.114 Recommendations and treat-
weight heparin is usually not clinically significant, nec- ment goals should be realistic and modifiable, have
essitating little modification to the dental protocol.132,133 clearly defined steps, and involve the personal care
However, a preoperative assessment of hemostasis givers as necessary.101,114 Prevention of oral disease
prior to invasive oral procedures should be undertaken caused by xerostomia, dietary changes, and ineffective
in patients taking oral anticoagulants. The risk of a throm- oral hygiene may be accomplished by reinforcing oral
boembolic event caused by the interruption of oral antico- care practices, topical application of fluoride, daily
agulants and subtherapeutic international normalized rinses with chlorhexidine, and frequent recalls.101,114
ratio (INR) frequently outweighs the benefits of postoper- Oral rehabilitation with fixed dental prostheses having
ative hemostasis in a patient undergoing uncomplicated easily cleansed embrasures is generally preferable
oral surgery.134,135 Local measures such as atraumatic owing to the inconvenience of daily placement and
surgical techniques, pressure, gelfoam, suturing, electro- removal of removable appliances for stroke patients.114
cautery, and topical hemostatic agents are often sufficient However, edentulous stroke patients with dentures
for control of excess bleeding136 and usually negate the should be instructed to wear their removable prostheses
need for reduction in dose or interruption of anticoagula- in order to preserve oral stereognosis.146 In addition, to
tion when INR is \3.5. For complicated oral surgery, reduce attrition and wear of the opposing dentition in
however, consultation with the physician is recommen- patients with stroke-related oral parafunction, fixed or
ded if INR is [3.5 or if the patient is on intravenous removable prostheses with porcelain occlusion are to
heparin. be avoided.114
Aspirin and other nonsteroidal antiinflammatory
agents may increase postoperative bleeding in patients CONCLUSION
taking oral anticoagulants.137,138 Acetaminophen-con- Cerebrovascular disease is the third leading cause of
taining products, cyclooxygenase-2especific inhibitors, death and a major cause of long-term disability in the
188 Fatahzadeh and Glick August 2006

United States. This article provides the dental commu- CD-ROM, 2001 edition. Philadelphia: Lippincott Williams &
Wilkins; 2001.
nity with an up-to-date understanding of the relevant 23. Bakshi R. Diffusion-weighted MRI as an evolving standard
issues pertaining to stroke. Dental management of of care in acute stroke. Neurology 2000;55:1595.
stroke patients is relatively straight forward. Major issues 24. Caplan LR. Treatment of acute stroke: still struggling. JAMA
of concern in dental management include screening 25. Fiebach JB, Schellinger PD, Geletneky K, et al. MRI in acute
for risk factors, hemostasis, drug actions and interactions, subarachnoid hemorrhage: findings with a standardized stroke
stress induced by the dental care, empathetic approach by protocol. Neuroradiology 2004;46:44-8.
26. Kidwell CS, Chaleta JA, Saver JL, et al. Comparison of MRI
the dental staff, and individualized oral care programs. and CT for detection of acute intracerebral hemorrhage.
JAMA 2004;292:1823-30.
27. Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic res-
REFERENCES onance imaging is accurate in hyperacute intracerebral hemor-
1. Warlow C, Sudlow C, Dennis M, Wardlow J, Sandercock P. rhage: a multicenter study on the validity of stroke imaging.
Stroke. Lancet 2003;362:1211-24. Stroke 2004;35:502-6.
2. Naidech AM, Weisberg LA. Treatment of chronic hypertension 28. Schellinger PD, Janson O, Fiebach JB, Hacke W, Sartor K.
for the prevention of stroke. South Med J 2003;96(4):359-62. A standardized MRI stroke protocol: comparison with CT in
3. Ingall TJ. Preventing ischemic stroke: current approaches to hyperacute intracerebral hemorrhage. Stroke 1999;30:765-8.
primary and secondary prevention. Postgrad Med 2000;107(6): 29. Lhermitte F, Gantier JC, Derouesne C. Nature of occlusions of
34-50. the middle cerebral artery. Neurology 1970;20:82-8.
4. Caplan LR. Now is an exciting time to care for stroke patients. 30. Wintermark M, Reichhart M, Tiran J-P, et al. Prognostic accur-
South Med J 2003;96(4):329-30. acy of cerebral blood flow measurement by perfusion computed
5. American Heart Association. Heart disease and stroke statistics, tomography, at the time of emergency room admission in acute
2005 update. Dallas: American Heart Association; 2005. stroke patients. Ann Neurol 2002;51:417-32.
6. Broderick J, Brott T, Kothari R, et al. The Greater Cincinnati/ 31. Bitar Sr, Kichura GM, Labovitz AJ. Cardiac sources of emboli:
Northern Kentucky Stroke Study: preliminary first-ever and The role of trans-esophageal echcardiography. Resid Staff
total incidence rates of stroke among blacks. Stroke 1998;29: Physician 1998;44:53-64.
415-21. 32. Straus SE, Majumdar SR, McAlister FA. New evidence for
7. Kirshner HS. Medical prevention of stroke. South Med J 2003; stroke prevention: scientific review. JAMA 2002;288:
96(4):354-8. 1388-95.
8. Leary MC, Saver JL. Incidence of silent stroke in the United 33. Petty GW, Brown RD, Whisnant JP, Sicks JA, OFallon WM,
States. Poster presented at the 26th American Heart Association Wiebers DO. Ischemic stroke subtypes. A population-based
Stroke Meeting, February 2001, Fort Lauderdale, Fla. study of functional outcome, survival, and recurrence. Stroke
9. Zweifler RM. Management of Acute Stroke. South Med J 2003; 2000;31:1062-8.
96(4):380-5. 34. Woo D, Gebel J, Miller R, et al. Incidence rates of first-ever
10. American Heart Association. Targeting the facts. Dallas: Amer- ischemic stroke subtypes among blacks: a population-based
ican Heart Association; 2002. study. Stroke 1999;30:2517-22.
11. Smith WS, Hauser SL, Easton JD. Cerebrovascular diseases. 35. Gorelick PB, Sacco RL, Smith DB, et al. Prevention of a first
In: Braunwald E, Hauser S, Fauci AS, Longo DL, Kasper DL, stroke. A review of guidelines and a multidisciplinary consen-
Jameson JL, editors. Harrisons principles of internal medicine. sus statement from the National Stroke Association. JAMA
15th ed. New York: McGraw-Hill; 2001. 1999;281:1112-20.
12. Feigin VL, Lawes CMM, Bennett DA, Anderson CA. Stroke 36. Hart RG, Sherman DG, Easton JD, Cairns JA. Prevention of
epidemiology: a review of population-based studies of inci- stroke in patients with nonvalvular atrial fibrillation. Neurology
dence, prevalence, and case-fatality in the late 20th century. 1998;51:674-81.
Lancet Neurol 2003;2:43-53. 37. Atrial Fibrillation Investigators. Risk factors for stroke and ef-
13. Toole JF, Sane DC, Betterman K. Stroke prevention: optimiz- ficacy of antithrombotic therapy in atrial fibrillation: analysis of
ing the response to a common threat. JAMA 2004;292(15): pooled data from five randomized controlled trials. Arch Intern
1885-7. Med 1994;154:1449-57.
14. Felberg RA, Naidech AM. The 5 Ps of acute ischemic stroke 38. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and
treatment: parenchyma, pipes, perfusion, penumbra and pre- intracranial hemorrhage: facts and hypotheses. Stroke 1995;
vention of complications. South Med J 2003;96(4):336-42. 26:1471-7.
15. Felberg RA, Burgin WS, Grotta JC. Neuroprotection and the 39. Wolf PA, Clagett GP, Easton JD, et al. Preventing ischemic
ischemic cascade. CNS Spectrs 2000;5:52-8. stroke in patients with prior stroke and transient ischemic at-
16. Toole J. Vascular diseases. In: Rowland L, editor. Merritts text- tack: AHA Scientific Statement. Stroke 1999;30:991-4.
book of neurology. Philadelphia: Lea & Febiger; 1989. 40. Hachinski VC, Lassen NA, Marshall J. Multi-infarct dementia:
17. Kelley RE, Minagar A. Cardioembolic stroke: an update. South a cause of mental deterioration in the elderly. Lancet 1974;2:
Med J 2003;96(4):343-9. 207-10.
18. Markesbery W. The central nervous system. In: Golden A, 41. Hier DB, Foulkes MA, Swiontoniowski M, et al. Stroke recur-
Powell DE, Jennings CD, editors. Pathology. Understanding rence within 2 years after ischemic infarction. Stroke 1991;22:
human disease. Baltimore: William & Wilkins; 1985. 155-61.
19. Frey JL, Jahnke HK, Bulfinch EW. Differences in stroke 42. PROGRESS Collaborative Group. Randomized trial of a peri-
between white, Hispanic, and Native American patients: the ndopril-based blood-pressure-lowering regimen among 6105
Barrow Neurological Institute Stroke Database. Stroke 1998; individuals with previous stroke or transient ischemic attack.
29:29-33. Lancet 2001;358:1033-41.
20. Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undeter- 43. Group PC. Randomized trial of a perindopril-based blood-
mined cause: The NINCDS Stroke Data Bank. Ann Neurol pressure-lowering regimen among 6105 individuals with pre-
1989;25:382-90. vious stroke or transient ischemic attack. Lancet 2001;358:
21. Xavier A, Qureshi A, Kirmani J, Yahia AM, Bakshi R. Neuro- 1033-41.
imaging of stroke: a review. South Med J 2003;96(4):367-78. 44. European Atrial Fibrillation Trial Study Group. Secondary pre-
22. Bakshi R, Ketonen L. Brain MRI in clinical neurology. In: vention in nonrheumatic atrial fibrillation after transient ische-
Joynt RJ, Griggs RC, editors. Bakers clinical neurology on mic attack or minor stroke. Lancet 1993;342:1255-62.
Volume 102, Number 2 Fatahzadeh and Glick 189

45. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted- 66. Broderick J, Lu M, Jackson C, et al. Apolioprotein E phenotype
dose warfarin versus low intensity, fixed dose warfarin plus and the efficacy of ifntravenous t-PA in acute ischemic stroke.
aspirin for high-risk patients with atrial fibrillation: Stroke Ann Neurol 2001;49:736-44.
Prevention in Atrial Fibrillation III randomized clinical trial. 67. del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley
Lancet 1996;348:633-8. HA, Gent M. PROACT: a phase II randomized trial of recom-
46. Secondary prevention in nonrheumatic atrial fibrillation after binant pro-urokinase by direct arterial delivery in acute middle
transient ischemic attack or minor stroke. EAFT (European cerebral artery strokePROACT Investigators: prolyse in acute
Atrial Fibrillation Trial) Study Group. Lancet 1993;342:1255-62. cerebral thromboembolism. Stroke 1998;29:4-11.
47. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic 68. Furlan A, Higashida R, Wechsler L, et al. Intraarterial pro-
therapy to prevent stroke in patients with atrial fibrillation: a urokinase for acute ischemic stroke. The PROACT II study:
meta-analysis. Ann Intern Med 1999;131:492-501. a randomized controlled trial. Prolyse in acute cerebral throm-
48. Broderick JP, Hacke W. Treatment of acute ischemic stroke part boembolism. JAMA 1999;282:2003-11.
II: neuroprotection and medical management. Circulation 2002; 69. Suarez JI, Sunshine JL, Tarr R, et al. Predictors of clinical
106:1736-40. improvement, angiographic recanalization, and intracranial
49. Ezekowitz MD, Levine JA. Preventing stroke in patients with hemorrhage after intra-arterial thrombolysis for acute ischemic
atrial fibrillation. JAMA 1999;281:1830-5. stroke. Stroke 1999;30:2094-100.
50. Gurbel PA, Bliden KP, Hiatt BL, OConnor CM. Clopidogrel 70. Bendszus M, Urbach H, Ries F, Solymosi L. Outcome after
for coronary stenting: response variability, drug resistance, local intra-arterial fibrinolysis compared with the natural course
and the effect pretreatment platelet reactivity. Circulation of patients with a dense middle cerebral artery on early CT.
2003;107:2908-13. Neuroradiology 1998;40:54-8.
51. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resis- 71. Fisher M, Schaebitz W. An overview of acute stroke therapy:
tance is associated with increased risk of recurrent athero- past, present and future. Arch Int Med 2000;160:3196-206.
thrombotic events in patients with acute myocardial 72. Sherman DG, for the STAT Writers Group. Defibrinogenation
infarction. Circulation 2004;109:3171-5. with viprinex (ancord) for the treatment of acute ischemic
52. Executive Committee for the Asymptomatic Carotid Athero- stroke [abstract]. Stroke 1999;30:234.
sclerosis Study. Endarterectomy for asymptomatic carotid 73. Marler JR, Lyden PD. The NINDS t-PA for acute stroke pro-
artery stenosis. JAMA 1995;273(18):1421-8. tocol. In: Lyden PD, editor. Thrombolytic therapy for Stroke.
53. North American Symptomatic Carotid Endarterectomy Trial Totowa (NJ): Humana; 2001. p. 297-308.
Collaborators. Beneficial effects of carotid endarterectomy in 74. National Institute of Neurological Disorders, Stroke rt-PA
symptomatic patients with high grade carotid stenosis. N Engl Study Group. Tissue plasminogen activator for acute ischemic
J Med 1991;325:445-53. stroke. N Engl J Med 1995;333:1581-7.
54. Cina CA, Clase CM, Haynes RB. Carotid endarterectomy 75. Chiu D, Krieger D, Villar Cordova C, et al. Intravenous tissue
for symptomatic carotid stenosis (Cochrane Review on plasminogen activator for acute ischemic stroke: feasibility,
CD-ROM). In: The Cochrane Library Issue 1. Oxford: The safety, and efficacy in the first year of clinical practice. Stroke
Cochrane Library; 2001. 1998;29:18-22.
55. European Carotid Surgery Trialists Collaboration. Randomized 76. Engelstein E, Margulies J, Jeret JS. Lack of t-PA use for acute
trial of endarterectomy for recently diagnosed carotid stenosis: ischemic stroke in a community hospital: high incidence of
final results of the MRC European Carotid Trial (ECST). Lancet exclusion criteria. Am J Emerg Med 2000;18:257-60.
1998;351:1379-87. 77. Chen ZM, Sandercock P, Pan HC, et al. Indications for
56. Ronning OM, Guldvog B. Stroke units versus general medical early aspirin use in acute ischemic stroke: a combined anal-
wards, I: twelve-and eighteenemonth survival: a randomized, ysis of 40,000 randomized patients from the Chinese Acute
controlled trial. Stroke 1998;29:58-62. Stroke Trial and the International Stroke Trial. On behalf of
57. Indredavik B, Bakke F, Slordahl SA, Rokseth R, Haheim LL. the CAST and IST Collaborative Groups. Stroke 2000;31:
Stroke unit treatment improves long-term quality of life: a ran- 1240-9.
domized, controlled trial. Stroke 1998;29:895-9. 78. Coull BM, Williams LS, Goldstein LB, et al. Anticoagulants
58. Langhorne P, Dennis MS. Stroke units: the next 10 years. and antiplatelet agents in acute ischemic stroke: Report of the
Lancet 2004;363:834-5. Joint Stroke Guideline Development Committee of the Ameri-
59. Broderick JP, Hacke W. Treatment of acute ischemic stroke part can Academy of Neurology and the American Stroke Associa-
I: recanalization strategies. Circulation 2002;106:1563-9. tion. Neurology 2002;59:13-22.
60. Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors 79. CAST: randomized placebo-controlled trial of early aspirin use
for severe hemorrhagic transformation in ischemic stroke pa- in 20,000 patients with acute ischemic stroke. CAST (Chinese
tients treated with recombinant tissue plasminogen activator: Acute Stroke Trial) Collaborative Group. Lancet 1997;349:
a secondary analysis of the European-Australian Acute Stroke 1641-9.
Study (ECASS II). Stroke 2001;32:438-41. 80. International Stroke Trial Collaborative Group. The Interna-
61. Quality Standard Subcommittee. American Academy of tional Stroke Trial (IST). A randomized trial of aspirin, subcu-
Neurology. Practice advisory: thrombolytic therapy for acute taneous heparin, both or neither among 19435 patients with
ischemia stroke: summary statement. Report of the Quality acute ischemic stroke. Lancet 1997;349:1569-81.
Standards Subcommittee of the American Academy of Neurol- 81. Atlantis, ECASS, NINDS rt-PA Study Group Investigators.
ogy. Neurology 1996;47:835-9. Association of outcome with early stroke treatment: pooled
62. NINDS t-PA Stroke Study Group. Generalized efficacy of t-PA analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke
for acute stroke: subgroup analysis of the NINDS t-PA Stroke trials. Lancet 2004;363:768-74.
Trial. Stroke 1997;28:2119-25. 82. Counsell C, Sandercock P. Low-molecular-weight heparins
63. Kwiatkowski T, Libman R, Frankel M, et al, and NINDS rt-PA or heparinoids versus standard unfractionated heparin for acute
Stroke Study Group. The NINDS rt-PA Stroke Study: sustained ischemic stroke. Cochrane Database Syst Rev 2000;2:CD000119.
benefit at one year. Stroke 1998;29:288. 83. The Publications Committee for the Trial of ORG 10172 in
64. Marler JR, Tilley BC, Lu M, et al. Early stroke treatment asso- Acute Stroke Treatment (TOAST) Investigators. Low molecular
ciated with better outcome; the NINDS rt-PA stroke study. Neu- weight heparinoid, ORG 10172 (danaparoid), and outcome af-
rology 2000;55:1649-55. ter acute ischemic stroke: a randomized controlled trial. JAMA
65. Fagan S, Morgenstern L, Petitta A, et al, and NINDS rt-PA 1998;279:1265-72.
Stroke Study Group. Cost-effectiveness of tissue plasminogen 84. Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low-molec-
activator for acute ischemic stroke. Neurology 1998;50:883-90. ular-weight heparin versus aspirin in patients with acute
190 Fatahzadeh and Glick August 2006

ischemic stroke and atrial fibrillation: a double-blind random- 110. Kimura M, Murata Y, Shimoda K, Robinson RG. Sexual
ized study. HAEST Study Group. Heparin in Acute Embolic dysfunction following stroke. Compr Psych 2001;42(3):
Stroke Trial. Lancet 2000;355:1205-10. 217-22.
85. Clark WM, Lutsep HL, Barnwell SL, Nesbit GM, Guterman 111. Yokota C, Minematsu K, Hasegawa Y, Yamaguchi T. Long-
LR, Teal P, et al. Multicenter feasibility study of an ultrasound term prognosis, stroke subtypes, after a first-ever stroke: a hos-
drug infusion microcatheter for treatment of acute ischemic pital-based study over a 20-year period. Cerebrovasc Dis 2004;
stroke [Abstract]. Stroke 2002;33:359. 18(2):111-6.
86. Ueda T, Sakaki S, Nochide I, Kumon Y, Kohno K, Ohta S. 112. Dombovy ML, Basford JR, Whisnant JP, Bergstralh EJ.
Angioplasty after intra-arterial thrombolysis for acute occlusion Disability and use of rehabilitation services following
of intracranial arteries. Stroke 1998;29:2568-74. stroke in Rochester, Minnesota. 1975-79. Stroke 1987;18:
87. Ernst R, Pancioli A, Tomsick T, et al. Combined intravenous 830-6.
and intra-arterial r-TPA in acute ischemic stroke. Stroke 2000; 113. Dobkin BH. Rehabilitation after stroke. N Engl J Med 2005;
31:2552-7. 352:1677-84.
88. Qureshi AI, Ali Z, Suri MF, et al. Intra-arterial third-generation 114. Little JW, Falace DA, Miller GS, Rhodus NL. Neurological
r-TPA (reteplase) for acute ischemic stroke. Neurosurgery 2001; disorders. In: Little JW, Falace DA, Miller GS, Rhodus NL,
49:41-50. editors. Dental management of the medically compromised
89. The Abciximab in Ischemic Stroke Investigators. Abciximab in patient. St Louis: Mosby; 2002. p. 417-38.
acute ischemic stroke: a randomized, double blind, placebo- 115. Wertz RT, La Point LL, Rosenbeck JC, editors. Apraxia of
controlled, dose-escalation study. Stroke 2000;31:601-9. speech in adults: the disorder and its management. New York:
90. Wojner AW, El-Mitwalli A, Alexandrov AV. Effect of head po- Grun & Stratton; 1984.
sitioning on intracranial blood flow velocities in acute ischemic 116. Gordon C, Langton HR, Wadw D. Dysphagia in acute stroke.
stroke: a pilot study. Crit Care Nurs Q 2002;24:57-66. Br Med J 1987;295:411-4.
91. Schwarz S, Georgiadis D, Aschoff A, et al. Effects of body po- 117. Shapiro S, Irwin M, Hamby CL. Dysphagia and the elderly:
sition on intracranial pressure and cerebral perfusion in patients an emerging challenge for dentistry. J Okla Dent Assoc 1991;
with large hemispheric stroke. Stroke 2002;33:497-501. 81:20-5.
92. Lewandowski C, Barsan W. Treatment of acute ischemic stroke. 118. Ciarrocca KN, Greenberg MS, Garfunkel A. Neuromuscular
Ann Emerg Med 2001;37:202-16. diseases. In: Greenberg M, Glick M, editors. Burkets oral med-
93. Hajat C, Hajat S, Sharma P. Effects of post-stroke pyrexia on icine diagnosis and treatment. Hamilton (BC): Decker; 2003. p.
stroke outcome: a meta-analysis of studies in patients. Stroke 592-605.
2000;31:410-4. 119. Scannapieco FA, Bush RB, Paju S. Association between perio-
94. Ginsberg MD, Busto R. Combating hyperthermia in acute dontal disease and risk for atherosclerosis, cardiovascular dis-
stroke: a significant clinical concern. Stroke 1998;29:529-34. ease and stroke. A systematic review. Ann Periodontol 2003;
95. Lees K. Neuroprotection is unlikely to be effective in humans 8(1):38-53.
using current trial designs. Stroke 2002;33:308-9. 120. Grau AJ, Buggle F, Ziegler C, Schwarz W, Meuser J, Tasman AJ.
96. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Association between acute cerebrovascular ischemia and
Kummer R. Malignant middle cerebral artery territory infarc- chronic and recurrent infection. Stroke 1997;28:1724-9.
tion: clinical course and prognostic signs. Archiv Neurol 1996; 121. Desvarieux M, Demmer RT, Rundek T, et al. Periodontal mi-
53:309-15. crobiota and carotid intima-media thickness: the Oral Infections
97. Kelly J, Rudd A, Lewis R, Hunt BJ. Venous thromboembolism and Vascular Disease Epidemiology Study (INVEST). Circula-
after stroke. Stroke 2001;32:262-7. tion 2005;111:576-82.
98. Dromerick AW, Abdul Khader SA. Medical complications 122. Syrjanen J, Peltola J, Valtonen V, Iivanainen M, Kaste M,
during stroke rehabilitation. Advances in neurology 2003;92: Huttunen JK. Dental infections in association with cerebral in-
409-13. farction in young and middle-aged men. J Intern Med 1989;
99. Iranzo A, Santamaria J, Berenguer J, Sanchez M, Chamorro A. 225:179-84.
Prevalence and clinical importance of sleep apnea in the first 123. Friedlander AH, Friedlander IK. Identification of stroke prone
night after cerebral infarction. Neurology 2002;58:911-6. patients by panoramic radiography. Aust Dent J 1998;43(1):
100. Sandberg O, Franklin KA, Bucht G, Gustafson Y. Sleep apnea, 51-4.
delirium, depressed mood, cognition, and ADL ability after 124. Carter L, Haller AD, Nadarajah V, Calamel AD, Aguirre A. Use
stroke. J Am Geriatr Soc 2001;49:391-7. of panoramic radiography among an ambulatory dental popula-
101. Ostuni E. Stroke and the dental patient. J Am Dent Assoc 1994; tion to detect patients at risk of stroke. J Am Dent Assoc 1997;
125:721-7. 128:977-84.
102. Helm-Estrabrook N, Albert M, editors. A manual for aphasic 125. Friedlander AH, Garrett NR, Chin EE, Baker JD. Ultrasono-
therapy. Austin (TX): Pro-Ed; 1991. p. 159. graphic confirmation of carotid artery atheromas diagnosed
103. Weisberg LA. Stroke and Struck: protecting the brain from via panoramic radiography. J Am Dent Assoc 2005;136(4):
cerebrovascular disease. South Med J 2003;96:331. 635-40.
104. Gupta A, Pansari K, Shetty H. Post-stroke depression. Int J Clin 126. Doris I, Dobranowski J, Franchetto AA, Jaeschke R. The
Pract 2002;56:531-7. relevance of carotid artery calcifications in patients on plain
105. Narushima K, Robinson RG. Stroke-related depression. Curr radiograph. Stroke 1993;24(9):1330-4.
Atheroscler Rep 2002;4:296-303. 127. Dempsey R, Diana AL, Moore R. Thickness of carotid artery
106. Swindle CS, Hammons J. Post-stroke depressions: neurologic, atherosclerotic plaque and ischemic risk. Neurosurgery 1990;
physiologic, diagnostic, and treatment implications. J Speech 27(3):343-8.
Hear Res 1991;34:325-33. 128. Wolf PA, DAgostino RB, Belanger AJ, Kannel WB. Probabil-
107. Kase CS, Wolf PA, Kelly-Hayes M, Kannel WB, Beiser A, ity of stroke: a risk profile from the Framingham Study. Stroke
DAgostino RB. Intellectual decline after stroke: the Framing- 1991;22:312-8.
ham Study. Stroke 1998;29:805-12. 129. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C.
108. Skoog I, Nilsson L, Palmertz B, Andreasson LA, Svanborg A. Long-term risk of recurrent stroke after a first-ever stroke. The
A population based study of dementia in 85-year-olds. N Engl Oxfordshire Community Stroke Project. Stroke 1994;25(2):
J Med 1993;328:153-8. 333-7.
109. Giaquinto S, Buzzelli S, Di Francesco L, Nolfe G. Evalua- 130. Leira EC, Chang KC, Davis PH, Clarke WR, Woolson RF,
tion of sexual changes after stroke. J Clin Psych 2003;64(3): Hansen MD, Adams HP Jr. Can we predict early recurrence
302-7. in acute stroke? Cerebrovasc Dis 2004;18:139-44.
Volume 102, Number 2 Fatahzadeh and Glick 191

131. Sacco RL, Foulkes MA, Mohr JP, Wolf PA, Hier DB, Price TR. 141. Rice PJ, Perry RJ, Afzal Z, Stockley IH. Antibacterial pre-
Determinants of early recurrence of cerebral infarction: The scribing and warfarin: a review. Br Dent J 2003;194(8):
Stroke Data Bank. Stroke 1989;20:983-9. 411-5.
132. Ardekian L, Gaspar R, Peled M, Brener B, Laufer D. Does low- 142. Searcy RL, Foreman JA, Myers HD, Bergquist LM. Anticoag-
dose aspirin therapy complicate oral surgical procedures? J Am ulant properties of tetracyclines. Antimicrobial Agent & Che-
Dent Assoc 2000;131:331-5. motherapy 1963;161:471-6.
133. Johnson-Leong C, Rada RE. The use of low-molecular-weight 143. ODonnell D. Antibiotic-induced potentiation of oral anticoag-
heparins in outpatient oral surgery for patients receiving antico- ulant agents. Med J Aust 1989;150:163-4.
agulation therapy. J Am Dent Assoc 2002;133(8):1083-7. 144. Dean RP, Talbert RL. Bleeding associated with concurrent
134. Wahl MJ. Myths of dental surgery in patients receiving antico- warfarin and metronidazole therapy. Drug Intell Clin Pharm
agulant therapy. J Am Dent Assoc 2000;131:77-81. 1980;14:864.
135. Jeske AH, Suchko GD. ADA Council on Scientific Affairs 145. Rose LF, Mealey B, Minsk L, Cohen DW. Oral care for patients
and Division of Science. Lack of a scientific basis for routine with cardiovascular disease and stroke. J Am Dent Assoc 2002;
discontinuation of oral anticoagulation therapy before dental 133(Suppl):37S-44S.
treatment. J Am Dent Assoc 2003;134(11):1492-7. 146. Leung KC, Pow EH, McMillan AS, Wong MC, Li LS, Ho SL.
136. Blinder D, Manor Y, Martinowitz U, Taicher S, Hashomer T. Oral perception and oral motor ability in edentulous patients
Dental extractions in patients maintained on continued oral with stroke and Parkinsons disease. J Oral Rehabil 2002;29:
anticoagulants. Oral Surg Oral Med Oral Pathol Oral Radiol 497-503.
Endod 1999;88:137-40.
137. Gage BF, Fihn SD, White RH. Warfarin therapy for an octoge-
narian who has atrial fibrillation. Ann Intern Med 2001;134(6): Reprint requests:
465-74. Dr Mahnaz Fatahzadeh, DMD
138. Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions Division of Oral Medicine
of warfarin with drugs and food. Ann Inter Med 1994;121: Department of Diagnostic Sciences
139. Wynn RL. Dental nonsteroidal antiinflammatory drugs and New Jersey Dental School
prostaglandin-based drug interactions, part one. Gen Dent 1992; University of Medicine & Dentistry of New Jersey
40(1):18-20. 110 Bergen Street
140. Carr MM, Mason RB. Dental management of anticoagulated Newark, NJ 07103
patients. J Can Dent Assoc 1992;58:833-44.