Chapter 18

CHAPTER 18
CEREBROVASCULAR DISEASE
Sharyl R. Martini, Thomas A. Kent
STROKE BASICS
1. What is a stroke?
Stroke is a focal disturbance of blood flow into or out of the brain, either primarily ischemic (87%) or
hemorrhagic (13%). Stroke is not a single disease but the end result of many different pathophysiolo-
gies leading to cerebrovascular occlusion or rupture. The key clinical feature of a stroke is very rapid
symptom onset: it hit me like a ton of bricks or like someone flipped a light switch. While the initial
onset is sudden, symptoms may fluctuate.
2. What is a transient ischemic attack (TIA)?
TIA is an abrupt onset neurologic deficit due to interruption of blood flow to a portion of the brain, fol-
lowed by complete symptom resolution. If the interruption continues long enough, an ischemic stroke
will result. By classic definition TIA deficits resolve within 24hours; however, contemporary definitions
define it as lasting under 1hour. In fact, most resolve within 5 to 15minutes. Transient neurologic
symptoms of unclear etiology are most appropriately referred to as spells; only those thought to be
due to brain ischemia should be referred to as TIAs.
3. Why is prompt recognition of TIAs important?
TIAs herald the possibility of a completed stroke: appropriate intervention may prevent strokes
and thus permanent disability. Ninety-day stroke rates for patients with TIA are >10% in some
series, with the greatest risk within 48hours to 7days. Longer symptom duration and presence
of large cerebral artery (e.g., carotid) stenosis are associated with higher risk of stroke following
TIA. All patients with a recent TIA (within 2weeks) need an expedited workup to determine cause.
4. How common are stroke and TIA?
According to the Centers for Disease Control, there are more than 795,000 strokes per year in
the United States, and it is the leading cause of disability. There are at least 250,000 TIAs each
year in the United States, but this number is likely an underestimate because many are not
reported.
5. What types of symptoms can strokes cause?
Focal weakness, numbness, facial asymmetry, or speech difficulties are classic presentations. Altered
level of consciousness, vertigo, and cranial nerve deficits are often seen with posterior circulation
(vertebrobasilar/brain stem) and cerebellar strokes. Table 18-1 lists common stroke syndromes.
Diminished level of consciousness is unusual for ischemic strokes.
6. How are stroke and TIA diagnosed?
Stroke and TIA are diagnosed clinically, and no imaging correlation is required for the acute diagnosis.
Imaging studies are performed to rule out other causes such as tumor and to determine whether there
is brain hemorrhage. Focal neurologic deficits with sudden onset should be considered vascular (e.g.,
stroke or TIA) until proven otherwise because of the possibility of recurrence or progression of the
deficit.
7. What are the most important risk factors for having a stroke?
The biggest predictor for ischemic stroke is prior stroke, and the second biggest risk factor is age. The
most important modifiable risk factor for stroke is hypertension. Other risk factors for ischemic stroke
include diabetes and smoking. A lipid profile with low high-density lipoprotein and high triglycerides is
also associated with ischemic stroke, whereas high low-density lipoprotein is most closely associated
with cardiac disease. Cardiac diseases such as atrial fibrillation and valvular disease are ischemic
stroke risk factors. The most significant risk factor for the commonest type of hemorrhagic stroke is
hypertension.
222
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Chapter 18 Cerebrovascular Disease 223
K EY POIN T S: ST ROK E B A S I C S
1 . The main clinical feature of stroke is sudden onset of a focal neurological deficit.
2. TIA serves as a warning for a completed stroke with the greatest risk for stroke in the first 72hours
to 2weeks following the TIA.
3. The biggest predictor of ischemic stroke is a prior stroke.
4. The most important modifiable risk factor for stroke is hypertension.
Table 18-1. Stroke Syndromes

SYNDROME SYMPTOMS
Anterior cerebral artery Contralateral leg>arm numbness and weakness; akinetic mutism/abu-
lia (especially bilateral infarcts)
Middle cerebral artery Ipsilateral eye deviation; contralateral face and arm>leg weakness,
sensory loss, contralateral hemianopsia; aphasia (left) or neglect (right)
Posterior cerebral artery Contralateral hemianopsia, memory loss
Top of the basilar Coma or somnolence/inattention, cortical blindness
Brain stem infarction Ataxia, vertigo, diplopia, crossed findings: contralateral weakness with
ipsilateral cranial nerve deficits
Cerebellar infarction Ataxia (unilateral appendicular or truncal), vertigo, nausea/vomiting
Lateral medullary Loss of pain and temperature sensation from the contralateral body and
(Wallenbergs) syndrome ipsilateral face; dysarthria, dysphagia, ataxia, hiccups
Pure motor* Contralateral face/arm/leg weakness
Pure sensory* Contralateral face/arm/leg sensory loss
Sensorimotor* Contralateral face/arm/leg weakness and sensory loss
Ataxic hemiparesis* Contralateral ataxia out of proportion to mild weakness
Clumsy hand dysarthria* Weak face and clumsy ipsilateral hand, dysarthria, dysphagia
*The five classic lacunar syndromes result from occlusion of a single penetrating artery, which may be caused by
small vessel vasculopathy, cardioembolism, or large artery atherosclerosis.
ISCHEMIC STROKECAUSES
8. What stroke syndromes are associated with occlusion of the cerebral arteries?
Stroke signs and symptoms depend on the part of the brain that is damaged. Although there is
person-to-person variation in arterial supply, classic syndromes are frequently seen (see Table 18-1).
9. What are the major etiologies of ischemic stroke?
The major etiologies of ischemic stroke are (1) cardioembolism; (2) small vessel vasculopathy (arterio-
losclerosis, lipohyalinosis) involving the penetrating arteries branching off the middle cerebral artery,
anterior cerebral artery, posterior cerebral artery, or basilar arteries; and (3) large vessel atheroscle-
rosis due to plaque rupture involving the intracranial or extracranial cerebral arteries. Table 18-2 lists
characteristics of these etiologic stroke subtypes.
10. What cardiac conditions are considered sources of cardioembolic stroke?
Cardiac conditions associated with stroke include atrial fibrillation or flutter, mechanical valves, septic
emboli, and marantic endocarditis. Patent foramen ovale (PFO) is prevalent and is not considered a
likely cardioembolic source unless left-to-right shunting and a venous clot can be demonstrated.
11. What are some less common causes of ischemic stroke?
Dissection of the cervical vessels needs to be considered, especially if there is neck/face pain or a history
of trauma. Horners syndrome may be seen with carotid injury. Illicit drug use (cocaine, stimulant-induced
spasm) can be a cause of ischemic stroke. Rarer causes of stroke include hypercoagulable states (e.g.,
active cancer, genetic clotting disorder, or autoimmune conditions such as lupus/antiphospholipid antibody
224Chapter 18 Cerebrovascular Disease
Table 18-2. Clues to the Most Common Ischemic Stroke Etiologies

ETIOLOGY CLINICAL FEATURES
Large vessel atherosclerosis Plaque rupture results in in situ large artery thrombosis or artery-to-
artery thromboembolism
Often occurs in early morning hours/on waking
History of TIAs in same vascular distribution
Symptoms may fluctuate
Cardioembolism History or clinical features of heart disease
Stroke symptoms are maximal at onset as clot is preformed
TIA symptoms are usually different from one another, representing
emboli to different vascular distributions
Often occurs during waking hours
Can be associated with Valsalva
Caused by embolism, usually from left atrial appendage (in the setting
of atrial fibrillation) or left ventricle (in the case of akinetic segment)
May have strokes of different ages in different vascular territories
Small vessel vasculopathy Strong association with hypertension and diabetes
Diameter <1.5cm
Occurs in subcortical regions such as basal ganglia, thalamus, or brain
stem
Never see cortical findings (aphasia, neglect)
Symptoms may fluctuate dramatically
May have TIAs with similar symptoms
Occlusion of small penetrating arteries is not always due to small vessel
etiologyalternate etiologies must be evaluated
TIA, Transient ischemic attack.
syndrome) and genetic disorders such as cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL) and fibromuscular dysplasia. PFO remains controversial as a
cause of stroke. Cases in which no specific cause is identified are called cryptogenic.
12. How do ischemic strokes appear on imaging?
On computed tomography (CT), most ischemic strokes eventually become visible as hypodensities of
the brain parenchyma (Fig. 18-1), but CT is largely normal for at least 6hours. The earliest CT signs
are loss of the cortical ribbon and gyral edema. On magnetic resonance imaging (MRI), strokes will
appear hyperintense on T2-weighted sequences. Diffusion-weighted imaging (DWI) detects cytotoxic
edema that accompanies ischemic cell death and can appear very shortly after onset of ischemia.
True diffusion positivity will appear dark on the apparent diffusion coefficient (ADC) map sequence.
Onset of DWI positivity may be delayed up to 48 to 72hours, particularly in the brain stem, and typi-
cally lasts 10 to 14days. The ADC map normalizes more quickly, often 4 to 7days after onset.
K EY POIN T S: IS C HE M I C S T R O K E C A US ES
1 . Determining stroke etiology is key to proper acute management and secondary prevention.
2. Major ischemic stroke subtypes include (1) large artery stroke due to atherosclerotic plaque rupture;
(2) cardioembolism, usually due to atrial fibrillation; and (3) small vessel vasculopathy.
3. Other causes of stroke include arterial dissection, hypercoagulable state, substance abuse, and
infectious/inflammatory conditions.
ISCHEMIC STROKEACUTE MANAGEMENT

13. What are the initial steps if ischemic stroke is suspected?
Head CT rules out hemorrhage, subdural hematoma, and tumor. It is the first and most important
test when evaluating for thrombolysis. In cases of suspected stroke, page the service responsible
A B
C D
E F
Figure 18-1. Computed tomography of strokes and stroke mimics. A, Lacunar ischemic stroke (arrow), typical of small
vessel vasculopathy. B, Multiple ischemic strokes of different ages in different vascular territories (arrows), typical
of cardioembolism. C, Subcortical intracerebral hemorrhage (arrow), typical of hypertensive hemorrhage. D, Cortical
intracerebral hemorrhage (arrow), typical of cerebral amyloid angiopathy. E, Subarachnoid hemorrhage (arrow), typical of
aneurysm rupture. F, Subdural hematoma (arrowhead) with a small amount of subarachnoid hemorrhage along the falx
(arrow). (Fromfor
Downloaded Levine G: Cardiology
lei zhou secrets, 4th edition, Philadelphia:
(zhoul20042003@yahoo.com) Elsevier,
at University of 2014.)
Virginia - JMU from ClinicalKey.com by
for rapidly addressing stroke (stroke team)every minute counts. Immediately check blood glucose
because hypoglycemia or hyperglycemia can cause focal neurologic deficits mimicking stroke. Also
obtain an electrocardiogram (ECG) and a troponin test, as initial cardiac workup can reveal atrial
fibrillation or myocardial infarction. Coagulation studies, basic chemistries, and complete blood count
should be drawn, but thrombolysis should not be delayed while awaiting these results unless there is
reason to suspect that they would be abnormal.
14. What are the Food and Drug Administration (FDA)-approved treatments for acute
ischemic stroke?
The only medication currently approved by the FDA to improve outcome after acute ischemic stroke
is intravenous tissue plasminogen activator (IV tPA), administered within 3hours of symptom onset.
Based on the European Cooperative Acute Stroke Study III (ECASS III), American Heart Association
guidelines recommend treatment in selected patients out to 4.5hours after symptom onset, but
this extended time window was not FDA approved. The earlier IV tPA is given, the better the clinical
outcome: an estimated 1million neurons die each minute that thrombolysis is delayed. Only alteplase
is approved for acute stroke thrombolysis.
15. How much do patients benefit from tissue plasminogen activator?
Eight stroke patients need to be treated with IV tPA to give one patient a complete or near-complete
recovery, and this number-needed-to-treat (NNT) takes into account the increased risk of hemor-
rhage after tPA administration. Patients of any age benefit from tPA: recent studies suggest that those
>80years may benefit more than younger patients.
16. What are contraindications to intravenous tissue plasminogen activator?
Contraindications are based on the National Institute of Neurological Disorders and Stroke (NINDS) tPA
trial: some, such as hemorrhage on CT head scan, are considered absolute, whereas others are rela-
tive (Table 18-3). The most frequent exclusion is time from when the patient was last seen normal (not
when symptoms were discovered)a particular problem for wake-up strokes. Patients with minor/
rapidly resolving deficits (possible TIAs) and seizure at stroke onset were excluded from the NINDS
trial in order to avoid treating conditions that would return to baseline without thrombolysis. However,
patients may be left disabled by mild or improving strokes, and seizures complicate acute strokes
approximately 15% of the time. Wording on the package insert for IV tPA changed slightly in 2015. It is
not yet clear whether this change will affect clinical guidelines.
17. How are patients monitored after administration of IV tPA?
Frequent clinical examinations are crucial, and blood pressure must be controlled to less than
180/105mm Hg to prevent bleeding into the infarcted brain tissue. Subcutaneous heparin and
antiplatelet agents are held for 24hours, until follow-up imaging confirms absence of hemorrhagic
conversion. Any change in exam warrants a stat CT head scan.
18. When should intra-arterial (IA) therapy be used for acute ischemic stroke?
The role for IA therapy is rapidly evolving. After three randomized controlled trials (RCTs) of older IA
devices failed to show improved clinical outcomes, four RCTs primarily using stent retriever devices
all demonstrated improved clinical outcomes, although it is not clear that the device is the sole expla-
nation for the better outcomes. Most but not all patients in these recent trials received IV tPA. Each
trial used different selection criteria, mostly enrolling patients without evidence of a completed stroke
on imaging and residual perfusion by vascular imaging. These trials are being carefully assessed, and
recommendations for the appropriate use of IA are pending. Until then, IA therapy with stent retriever
devices is reasonable in patients with device-accessible proximal large vessel occlusions without
early ischemic changes on brain imaging. Given the dangers of reperfusion injury and device-related
complications (11% to 16%), rapid therapy and careful patient selection are vital.
19. What if the patient is not a candidate for intravenous tissue plasminogen
activator?
In patients not treated with thrombolysis, aspirin (orally or rectally) reduces the chances of recurrent
stroke when given within 48hours. Optimal blood pressure for nonthrombolysed patients is not known
but is often permitted to run high as long as there are no signs of hypertensive end-organ damage.
This permissive hypertension is theoretically designed to increase perfusion of brain tissue at con-
tinued risk for ischemia, but it is not clear that this strategy improves outcomes. Avoid sudden drops or
rises in blood pressure: relative hypotension associated with neurologic worsening should be treated
with IV fluids. Lowering the head of the bed and administering vasopressors may also be considered.
Chapter 18 Cerebrovascular Disease226.e1
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA
Stroke Study Group. N Engl J Med 333(24):1581-1587, 1995.
Hacke W, Kaste M, Bluhmki E, Brozman M, Dvalos A, Guidetti D, etal.: Thrombolysis with alteplase 3 to 4.5hours after
acute ischemic stroke. N Engl J Med 359(13):1317-1329, 2008.
Table 18-3. Contraindications to Intravenous Tissue Plasminogen Activator

Absolute Contraindications
Greater than 4.5hours from the time patient was last seen normal
Initial head CT suggests time of onset is inaccurate
Suggestion of intracranial hemorrhage on pretreatment imaging
Subarachnoid hemorrhage
Intracerebral hemorrhage
Intracranial neoplasm or arteriovenous malformation
Active internal bleeding
Uncontrolled hypertension greater than 185/110mm Hg despite antihypertensive treatment
Current bacterial endocarditis
Head trauma, intracranial/intraspinal surgery, or myocardial infarction within 3months
Known bleeding diathesis:
INR>1.7 or PT>15seconds
Platelets <100,000 mm3
Heparin within 48hours if PTT is elevated
PTT outside of the normal range
Dose of nonwarfarin oral anticoagulant within past 12hours
Relative Contraindications
Minor or rapidly resolving deficits
Seizure
Major surgery in the previous 2weeks
GI or urinary hemorrhage in the previous 3weeks
Puncture at noncompressible site within 7days (including lumbar puncture)
PTT, Partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; GI, gastrointesti-
nal; CT, computed tomography.
20. What are the major clinical concerns in the initial days following an ischemic stroke?
Clots may propagate, particularly those due to large artery atherosclerosis. Expeditious identification of this
subtype is recommended. The most life-threatening complication of stroke is herniation due to cerebral
edema, which manifests 12hours to 5days after onset. Clinical signs include somnolence, pupillary dilation
from third nerve compression, and signs of increased intracranial pressure (nausea, vomiting). Herniation
may occur either upward or downward through the tentorium or under the falx cerebri. Large hemispheric
and cerebellar strokes are most likely to cause herniation. Manipulation of serum osmolarity (mannitol,
hypertonic saline) or hyperventilation may be used, though definitive treatment is surgical decompression.
21. When is hemicraniectomy recommended?
Patients with malignant middle cerebral artery occlusion are at risk of death from cerebral edema and
herniation. Every 2 hemicraniectomy procedures for malignant MCA infarction saves 1 life. Although
fewer people die, less than 10% achieve functional independence. Surgical decompression is often
suggested for large strokes within the cerebellar hemispheres as patients tend to recover well from
these strokes if they survive the acute period. Early consultation with neurosurgery is suggested.
22. What is hemorrhagic transformation (hemorrhagic conversion)?
Ischemic strokes can develop a hemorrhagic component, especially if they are large or if the degree
of ischemia is severe. This hemorrhagic transformation occurs because all tissue downstream of
an ischemic stroke becomes ischemicbrain and vasculature. In many cases, blood flow to the
ischemic area is reestablished too late to benefit the brain and returns via weakened, damaged ves-
sels. These vessels may leak, resulting in petechial hemorrhage, or burst, resulting in a hematoma.
Hemorrhagic transformation is most likely in the first days to a week after stroke. This is why clinical
worsening in an ischemic stroke patient should be immediately evaluated with noncontrast head CT.
K EY POIN T S: IS C HE M I C S T R O K E A C UT E M A N A G E M ENT
1 . Noncontrast CT is used acutely to rule out hemorrhage or tumor (not to diagnose stroke).
2. For IV tPA eligibility, stroke onset is defined as the time the patient was last seen normal, not when
he or she was discovered to have symptoms.
3. Clinical deterioration in the acute period following stroke may be due to clot propagation (large ves-
sel subtype), cerebral edema/herniation, or hemorrhagic transformation.
ISCHEMIC STROKEWORKUP AND MANAGEMENT

23. What are the goals of hospitalization for an ischemic stroke?
The goals of stroke hospitalization are to (1) prevent complications such as stroke progression, aspira-
tion pneumonia, and pulmonary embolism; (2) develop a plan for functional recovery with the help of
physical, occupational, and speech therapy; and (3) determine the stroke mechanism in order design
an optimal secondary stroke prevention strategy.
24. How can systemic complications of stroke be prevented?
In all cases of stroke, ensure adequate deep vein thrombosis (DVT) prophylaxis to prevent pulmonary
emboli. Keep patients nil per os (NPO) until safe swallowing can be confirmed to prevent aspiration and
subsequent pneumonia. Frequent turning prevents skin breakdown. Catheters should be removed as soon
as possible. Patients should be mobilized as soon as safely possible, although many are at high risk of falls
and may need constant supervisionthose with neglect in particular as they are unaware of their deficits.
25. What is considered a complete ischemic stroke workup?
Patients with anterior circulation strokes need urgent carotid imaging. Intracranial as well as extra-
cranial imaging is performed in most cases. MRI is useful for detecting strokes not apparent on head
CT: small strokes in multiple vascular distributions point to a cardioembolic source. In patients with
suspected cardioembolism, echocardiogram (ECG) is indicated. All patients should have telemetry
for atrial fibrillation identificationECGs are inadequate for detection of this important risk factor.
Implantable event monitors reveal subclinical atrial fibrillation in a substantial proportion of patients
with cryptogenic stroke and are warranted in cases where clinical suspicion is high.
26. How would stroke workup differ for a young person or someone without the usual
stroke risk factors?
Stroke workup in the young patient begins with a detailed history including personal or family history
of clotting, autoimmune disease, trauma, and cardiac disease. Careful examination of eyes and skin
may provide clues to neurofibromatosis, Fabrys disease, connective tissue diseases, or endocarditis.
As young stroke patients are more likely to have cardiac abnormalities, a detailed cardiac evaluation
including transesophageal echo should be performed. MRI brain, vessel imaging, and hypercoagulable
workup are standard, as are toxicology, autoimmune, and vasculitis labs (erythrocyte sedimentation
rate, C-reactive protein, antinuclear antibody, antineutrophil cytoplasmic antibody, rheumatoid factor,
complement). Rapid plasma reagin and human immunodeficiency virus testing are vital. Lumbar
puncture may reveal additional infectious or inflammatory conditions.
27. What is a hypercoagulable workup?
Family history of clotting, miscarriages, or a paucity of vascular risk factors should raise suspicion
for a hypercoagulable state. Hormone use (oral contraceptives, testosterone replacement, hormone
replacement) is associated with an increased thrombotic risk and should be specifically sought from
history. Laboratory tests include antithrombin III, protein C, protein S, activated protein C resistance/
factor V Leiden mutation, and prothrombin mutation. Lupus anticoagulant and anticardiolipin or beta2
glycoprotein antibodies point to antiphospholipid antibody syndrome. Cancer produces a hypercoagu-
lable state, so malignancy evaluation should be considered.
28. What is the best strategy to prevent additional strokes?
The best strategy depends on the causative etiology: options for carotid stenosis, intracranial stenosis,
and atrial fibrillation are presented below. Small vessel disease secondary stroke prevention relies
solely on aggressive risk factor management. Goals for secondary stroke prevention include target
blood pressure <140/90, antiplatelet or anticoagulant as appropriate, statin, hemoglobin A1C <7,
smoking cessation, regular exercise, and BMI <25. Obstructive sleep is associated with increased
stroke risk independent of its association with hypertension, so treatment seems prudent.
29. What options exist for evaluating cerebral vessels?

Carotid duplex ultrasound is cost-effective but inadequate for evaluation of intracranial vessels or the
posterior circulation. Transcranial Doppler ultrasound evaluates intracranial vessels but is operator
dependent and not widely available. CT angiogram is fast, readily available, and provides detailed
information from the aortic arch to the intracranial vessels. Disadvantages include radiation exposure
and the need for iodinated contrast. MR angiogram also evaluates the entire cerebrovascular tree,
although motion artifacts can obscure the arch and great vessel origins. Its major disadvantage is the
need to lie still for 30 to 45minutes. Gadolinium-based contrast agents provide additional resolution
but cannot be given in renal insufficiency due to the possibility of systemic sclerosis.
30. How should carotid stenosis be managed?
Patients with symptomatic carotid stenosis >70% should be treated with carotid endarterectomy
(CEA) or stenting within 2weeks of a TIA or nondisabling stroke: risk of recurrent stroke is 15% per
year, and CEA cuts it in half. Patients with 50% to 70% symptomatic stenosis benefit less from carotid
intervention but have the same upfront procedure risk. Asymptomatic patients with 60% stenosis
have a 2% to 4% annual stroke rate that is cut in half after CEA; however, upfront risk of death or
stroke from the procedure is 3% to 6%, so overall benefit is less than for symptomatic disease. The
Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) comparing CEA with stenting
showed higher stroke and death rates in the stenting group, but higher myocardial infarction rates
with CEA: overall rates of the combined endpoint were not different. Older patients fared better with
CEA than carotid stenting, and quality of life was better in those with myocardial infarction than in
those with stroke.
31. How should intracranial stenosis be managed?
In the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial
Stenosis (SAMMPRIS) trial, patients with recent mild stroke or TIA due to 70% to 99% intracranial
stenosis were randomized to stenting plus aggressive medical management, versus aggressive medi-
cal management alone. All subjects received aspirin plus clopidogrel for 90days, followed by aspirin
alone. In addition to blood pressure and lipid goals, lifestyle coaches developed goals for weight loss,
regular exercise, and smoking cessation with each participant. The trial was stopped early because
14.7% in the stenting arm had a stroke within 30days (most within 1day of stenting) compared with
5.8% in the medical management group; 1-year stroke rates were 20% and 12.2%, respectively. As
such, intracranial atherosclerosis is now managed medically.
32. What if the patient has a PFO?
PFOs are present in up to 25% of the population and in most cases confer little if any stroke risk.
Large PFOs with a right-to-left shunt and those with atrial septal aneurysms are of greater concern.
If a concerning PFO is found the next step is to identify a venous source. Pelvic vein MRI may identify
DVTs not apparent by standard vascular ultrasound techniques. PFO closure has been hotly debated:
CLOSURE I compared PFO closure to best medical management in subjects with cryptogenic stroke
and did not find a benefit of PFO closure after 2years of follow-up. Most subjects with recurrent stroke
had evidence of a mechanism other than paradoxical embolism. At this point, PFO closure is best done
in the setting of an RCT.
33. How well do anticoagulants work to prevent stroke in the setting of atrial
fibrillation?
All patients with stroke and atrial fibrillation merit consideration for long-term anticoagulation because
it reduces ischemic stroke by more than 60%. Other high-risk groups include those age >75 (especially
women), and those with poorly controlled hypertension, diabetes, poor left ventricular function, or
recent heart failure. The CHA2DS2-VASc risk stratification scheme integrates risk factors to assist in the
decision for anticoagulation therapy: the greater the number of risk factors, the higher the risk of stroke.
Stroke or TIA automatically places a patient in the high-risk category, so secondary prevention of stroke
in patients with atrial fibrillation should involve oral anticoagulation unless there is a contraindication.
34. Do patients who have ablation or surgery for atrial fibrillation still need
anticoagulation?
Restoring sinus rhythm, resecting the left atrial appendage, and transcatheter closure of the left atrial
appendage opening have thus far not demonstrated a sufficient reduction of stroke risk to warrant
discontinuing anticoagulation. Atrial Fibrillation Follow-up Investigation of Rhythm Management
(AFFIRM) found that restoring sinus rhythm did not reduce stroke risk. The Watchman trial similarly
Chapter 18 Cerebrovascular Disease 229.e1
Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, etal.: Stenting versus aggressive medical therapy for
intracranial arterial stenosis. N Engl J Med 365(11):993-1003, 2011.
did not find a reduction in stroke risk; additional device trials are ongoing. The Left Atrial Appendage
Occlusion Study III is an ongoing phase 3 trial comparing surgical excision of the left atrial appendage
with best medical therapy. At this time, anticoagulation is the only intervention proven to reduce stroke
in the setting of atrial fibrillation.
35. What about anticoagulation in patients at high risk for bleeding?
Although elderly patients are at high risk for bleeding they are also at high risk for stroke from atrial fibril-
lation; thus, age is not a contraindication to anticoagulation. Contraindications include history of severe
gastrointestinal (GI) bleeding, history of falls, or an extremely high fall risk. The HAS-BLED score is a
simple method for assessing bleeding risk. After stroke, many patients are at risk for falls: as they recover,
reconsider anticoagulation. The decision for anticoagulation should be an ongoing collaborative discussion
of the risks, benefits, and monitoring schedule so that the patient can make an informed decision.
36. What is the role of the new anticoagulants (dabigatran, rivaroxaban, apixaban)?
New oral anticoagulants include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors
apixaban and rivaroxaban. The benefit of these agents over warfarin is due to better stroke prevention
as well as lower bleeding risk. Intracerebral hemorrhage, the most dreaded complication of antico-
agulation, was substantially reduced. Dabigatran and rivaroxaban had higher rates of GI bleeding
than warfarin; apixaban showed no such trend. Dabigatran showed a small but consistent increase in
myocardial infarction, although it decreased overall vascular events and mortality. One disadvantage
is a higher risk of thrombotic events when these agents are stopped, so patients must be extremely
compliant. Significant renal impairment is a contraindication.
37. How soon after a stroke should anticoagulation be started?
Large strokes and those due to cardioembolism are most likely to bleed. As such, it is common prac-
tice to wait 1month after a large stroke before initiating anticoagulation for atrial fibrillation. Patients
with very small cardioembolic strokes may be started on anticoagulation within 1 to 2days. In patients
with large strokes at high risk for embolization (mechanical valves, cardiac thrombus), anticoagula-
tion may be started cautiously after 5 to 15days. Retrospective data suggest bridging with heparin or
low-molecular-weight heparin causes more bleeding. In the absence of a hypercoagulable state, it is
acceptable to start warfarin at low doses to achieve therapeutic anticoagulation slowly. Some clini-
cians suggest aspirin until an international normalized ratio (INR) of 2 is achieved.
38. How are antiplatelet agents used after stroke?
Patients who do not meet criteria for anticoagulation should receive antiplatelet therapy: aspirin,
clopidogrel, or extended-release dipyridamole plus aspirin. All are similarly efficacious, decreasing
stroke risk 14% to 18%. Ensuring adherence is probably more important than the agent used, so
choice should be guided by comorbidities, tolerability, and cost. Clopidogrel may be preferred for
patients with peripheral vascular disease, chronic nonsteroidal antiinflammatory drug use, or drug-
eluting stents. Aspirin is a good choice when not contraindicated, particularly for patients on proton
pump inhibitors or when the cost of alternatives would hinder compliance. Antiplatelet therapy should
be initiated immediately in patients who are not tPA candidates and do not have any hemorrhagic
component. Wait 24hours after tPA to start antiplatelet medications.
39. Should aspirin and clopidogrel be used together for stroke prevention?
Aspirin should not be combined with clopidogrel for long-term secondary stroke prevention due to
unacceptably high bleeding risk without additional protection from strokes (SPS3 [Secondary Preven-
tion of Small Subcortical Strokes] and MATCH (Management of Atherothrombosis with Clopidogrel
in High-risk patients) trials). The CHANCE (Clopidogrel in High-risk patients with Acute Nondisabling
Cerebrovascular Events) trial found that aspirin plus clopidogrel for the 21days after stroke reduced
the odds of a second stroke within 90days. Most participants were from China where blood pres-
sure control is less frequently achieved. In the absence of definitive data, either short-term dual
antiplatelets or a single antiplatelet agent may be used for secondary stroke prevention. Patients on
dual antiplatelets for other indications may be continued on this combination after stroke with the
understanding that bleeding risk may be elevated.
40. Should aspirin be added to anticoagulation?
In patients requiring anticoagulation, bleeding risk increases with the addition of antiplatelet agents.
Except in cases of unstable coronary disease or mechanical valves, this increased bleeding risk is not
offset by a decrease in thrombotic events. Because ischemic stroke and intracerebral hemorrhage
increase dramatically with age, patients presenting with stroke are quite different from those present-
ing with acute coronary syndromes. As such, it is not valid to extrapolate stroke secondary prevention
from cardiac studies, as the MATCH trial exemplified. The decision to add aspirin to anticoagulation is a
difficult one, best made collaboratively among patient, neurologist, and cardiologist.
41. What if a patient has a stroke while taking an antiplatelet agent?
The notion of treatment failure has been proposed if a patient has a stroke or TIA while on a specific
agent. Genetic variation in antiplatelet response has been convincingly established for clopidogrel
and suggested for aspirin, but genetic testing is not routinely used in the selection of antiplatelet
agents. Currently, only limited retrospective data support changing to a different antiplatelet agent
after stroke. In the absence of definitive data, it may be more fruitful to address risk factor reduction
strategies and medication adherence. The role of laboratory platelet inhibition measures in choice of
antiplatelet agent remains to be established.
42. How well do patients recover following ischemic stroke?
Younger patients and those with smaller strokes tend to recover better, but there is remarkable person-
to-person variation. The best predictor of how a person will recover is the initial stroke severity and the
trajectory of recovery within the first weeks following the stroke. Much of the recovery occurs within
the first month, and the majority of recovery is complete by 3months. Recovery occurs after 3months,
especially for higher cortical function such as language, but at a slower pace. In cases of motor weak-
ness, recovery usually begins proximally and moves distally as recovery progresses. The FLAME (Family
Lifestyle, Activity, Movement and Eating) study found that fluoxetine initiated within 5 to 10days of
ischemic stroke was associated with lower rates of depression and improved motor recovery.
43. What are additional considerations when stroke patients return for follow-up?
Stroke follow-up visits should address new neurologic symptoms, stroke risk factors, depression, and recov-
ery. New neurologic symptoms may represent stroke, TIA, or seizure. Those with ongoing paralysis should
be assessed for conditions that may adversely affect their recovery including depression, spasticity, shoulder
subluxation or frozen shoulder, and post-stroke pain. Complex regional pain syndrome is characterized by
intermittent symptoms (cold feeling, purplish mottled skin, swelling) in the areas affected by the stroke.
K EY POIN T S: IS C HE M I C S T R O K E W O R K UP A N D M A N A GEMENT
1. Diffusion-weighted MRI can identify cytotoxic edema from ischemic strokes but may be negative in
small strokes or TIAs.
2. CT angiogram or MR angiogram can suggest stroke etiology by identifying arterial thrombus, dissec-
tion, or atherosclerotic stenosis.
3. Symptomatic carotid stenosis requires urgent intervention; asymptomatic carotid stenosis does not.
4. For strokes due to atrial fibrillation, anticoagulation decreases risk of a subsequent stroke by 60%.
HEMORRHAGIC STROKE SUBTYPES

44. What are the major types of hemorrhagic strokes?
Hemorrhagic strokes include subarachnoid hemorrhage (SAH, usually due to aneurysm rupture) and
parenchymal intracerebral hemorrhage (ICH). Overall, approximately 6% of strokes are due to deep
ICH, 3% are due to lobar ICH, and 3% are due to SAH. Although ischemic strokes are more frequent,
hemorrhagic strokes have a higher morbidity and mortality. Because subdural and epidural hemato-
mas are extra-axial, these bleeds are not considered strokes (see Fig. 18-1).
45. How can you distinguish hemorrhagic from ischemic strokes?
Clinical clues pointing to a hemorrhagic etiology include an early diminished level of consciousness
and worsening of symptoms over minutes to hours. Headache is more common in hemorrhagic stroke
and is the cardinal feature of SAH. Head CT is the most reliable way to distinguish ischemic and
hemorrhagic strokes, with acute hemorrhage appearing hyperdense (see Fig. 18-1).
46. Why is the location of an intraparenchymal hemorrhage important?
Intraparenchymal ICHs are classified by their location: deep or subcortical ICHs are associated with
uncontrolled hypertension in 60% of cases; lobar or cortical ICHs are more concerning for underlying
mass, arteriovenous malformation, or cerebral amyloid angiopathy.
47. What is the typical clinical profile of a hypertensive hemorrhage?

Hypertensive hemorrhages occur most frequently in patients with a history of poorly controlled
hypertension. They are associated with small vessel ischemic changes and microbleeds of the
basal ganglia, deep white matter, brain stem, and cerebellum. These hemorrhages occur more
frequently and at younger ages in black and Hispanic individuals.
48. What is the typical clinical profile of cerebral amyloid angiopathy?
Cerebral amyloid angiopathy (CAA) is most common in elderly Caucasian individuals. It is associated
with Alzheimers disease, particularly in those carrying the ApoE4 allele. CAA hemorrhages have a
predilection for the occipital cortex but may occur in any cortical region.
49. How is ICH managed?
ICHs are managed by reversing coagulopathy. Clot evacuation for lobar ICHs and ventriculostomy in
cases with hydrocephalus or intraventricular blood may be considered. Intraventricular clot lysis with
tPA is being studied. High blood pressure is associated with hematoma expansion and rebleeding,
so systolic blood pressure is maintained below 180mm Hg. The INTERACT (intensive blood pressure
Reduction in Acute Cerebral haemorrhage Trial) and ATACH (Antihypertensive Treatment of Acute
Cerebral Hemorrhage) trial have found that further lowering systolic blood pressure to 140mm Hg is
safe and feasible, but clinical benefit has not been demonstrated. DVTs are common following ICH,
and pneumatic compression devices are more effective than compression stockings alone. Some
practitioners add subcutaneous heparin after 48hours.
50. What is considered a complete workup for ICH?
The urgency and possibly extent of workup will depend on the clinical scenario: an octogenar-
ian with Alzheimers disease and an occipital ICH may require less etiologic workup than would a
65-year-old with a basal ganglia ICH and decades of poorly controlled hypertension. Cases that do
not fit these profiles require vessel imaging to evaluate for arteriovenous malformations (AVMs) or
aneurysms and MRI with contrast to evaluate for tumors. Aneurysm rupture can cause intraparen-
chymal hemorrhage, so it is important to consider SAH as well as cerebral venous sinus thrombosis
(see below). If initial workup is unrevealing, repeat studies after the hematoma has resolved (2 to
3months) may be useful.
51. What causes SAH?
SAH can be traumatic but is commonly caused by a ruptured berry aneurysm. Hypertension, larger
size (especially >7mm), and posterior circulation location are associated with aneurysm rupture.
Hypertension and smoking contribute to aneurysm growth. Polycystic kidney disease and inherited
connective tissue defects are also associated with intracranial aneurysms.
52. How is SAH diagnosed?
SAH due to aneurysm rupture classically presents with the worst headache of ones life; loss of
consciousness, nausea/vomiting, nuchal rigidity, and focal neurologic signs are also common.
Although large amounts of subarachnoid blood are readily apparent on CT, even small amounts of
subarachnoid blood can provoke symptoms. Detection of these small sentinel bleeds are vital, as
they herald aneurysm rupture. Sensitivity of CT declines with time from symptom onset, so spinal fluid
should be examined for red blood cells or xanthochromia if head CT is negative and clinical suspicion
high. Because of its ready availability, CT angiogram is often performed acutely in lieu of conventional
angiogram for surgical planning.
53. How is SAH managed?
SAH is managed by securing the aneurysm as soon as possible and monitoring for vasospasm
in an intensive care unit setting for up to 2weeks. Vasospasm may be evaluated by transcranial
Doppler or CT angiogram. Cardiac arrhythmias are common following SAH. Pneumatic compres-
sion devices and subcutaneous heparinoid (once the aneurysm is secure) are used for DVT
prophylaxis.
CEREBRAL VENOUS SINUS THROMBOSIS
54. What causes cerebral venous sinus thrombosis (CVST)?

CVST is caused by clot formation in large draining veins or dural sinuses. Congenital or acquired
hypercoagulable states, dehydration, and oral contraceptive use are associated with CVST.
55. How is CVST diagnosed?

CVSTs usually present with continuous headache, worse in the morning or after lying down. If intra
cranial pressure is elevated, patients may experience impaired consciousness or blurry vision due
to cerebral edema and subsequent papilledema. Venous infarctions are frequently hemorrhagic and
can result in focal neurologic signs and symptoms that do not respect typical arterial distributions.
Seizures are common and may be a presenting symptom. A high index of suspicion is needed to
diagnose and appropriately treat CVST, as cases may be easily missed during the course of a standard
ischemic or hemorrhagic stroke workup. CVST is diagnosed with CT or MR venogram.
56. How is CVST managed?
Venous sinus thrombosis is most commonly managed by anticoagulation, which may be counterin-
tuitive in cases of venous infarction with hemorrhage. Other options include mechanical thrombec-
tomy and intrasinus thrombolysis, especially if the patient is worsening despite anticoagulation.
This is a fairly uncommon condition, so no RCTs have been performed to compare treatment
strategies.
K EY POIN T S: HE M ORR H A G I C S T R O K E A N D C E R EB R A L V ENOU S S INU S

THROM BOS IS
1 . Hemorrhagic strokes are more likely to be fatal than ischemic strokes.
2. Hemorrhagic stroke location suggests etiology: deep=hypertensive; lobar=CAA, AVM, or tumor;
SAH=aneurysm rupture or trauma.
3. Clinically hemorrhagic strokes present with headache, diminished level of consciousness, and
(in the case of SAH) meningeal signs.
4. CVST may cause venous infarctionoften hemorrhagicwhich is treated with anticoagulation.
References available online at expertconsult.com.
WEB SIT E S
http://www.merck.com/mmpe
http://emedicine.medscape.com
Bibliography
1. Martini SR, Grossman AW, Kent TA: Stroke. In Levine GN (ed): Color Atlas of Cardiovascular Disease, Philadelphia,
Jaypee Brothers Medical Publishers, 2015.

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Table 18-1. Stroke Syndromes

Table 18-2. Clues to the Most Common Ischemic Stroke Etiologies

ISCHEMIC STROKEACUTE MANAGEMENT

Table 18-3. Contraindications to Intravenous Tissue Plasminogen Activator

ISCHEMIC STROKEWORKUP AND MANAGEMENT

29. What options exist for evaluating cerebral vessels?

HEMORRHAGIC STROKE SUBTYPES

47. What is the typical clinical profile of a hypertensive hemorrhage?

CEREBRAL VENOUS SINUS THROMBOSIS

54. What causes cerebral venous sinus thrombosis (CVST)?

55. How is CVST diagnosed?

K EY POIN T S: HE M ORR H A G I C S T R O K E A N D C E R EB R A L V ENOU S S INU S

References available online at expertconsult.com.

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CHAPTER 18

Table 18-1. Stroke Syndromes

Table 18-2. Clues to the Most Common Ischemic Stroke Etiologies

ISCHEMIC STROKEACUTE MANAGEMENT

Table 18-3. Contraindications to Intravenous Tissue Plasminogen Activator

ISCHEMIC STROKEWORKUP AND MANAGEMENT

29. What options exist for evaluating cerebral vessels?

HEMORRHAGIC STROKE SUBTYPES

47. What is the typical clinical profile of a hypertensive hemorrhage?

CEREBRAL VENOUS SINUS THROMBOSIS

54. What causes cerebral venous sinus thrombosis (CVST)?

55. How is CVST diagnosed?

K EY POIN T S: HE M ORR H A G I C S T R O K E A N D C E R EB R A L V ENOU S S INU S

References available online at expertconsult.com.

Potrebbero piacerti anche

Table 18-1. Stroke Syndromes

Table 18-2. Clues to the Most Common Ischemic Stroke Etiologies

Table 18-3. Contraindications to Intravenous Tissue Plasminogen Activator

29. What options exist for evaluating cerebral vessels?

47. What is the typical clinical profile of a hypertensive hemorrhage?

54. What causes cerebral venous sinus thrombosis (CVST)?

55. How is CVST diagnosed?