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Cerebrovascular Disease
“I am impressed with this unique format of case reports that are each instructive
of a clinical lesson, including modern brain imaging and intravascular approaches
to the diagnosis and treatment of brain lesions. The numerous figures are ample,
clear, and helpful. This little book will find its way in to the pockets of residents
everywhere.”
—Lewis P. Rowland, MD, Neurological Institute, Columbia University
Medical Center, New York, NY
“Dr. Chong’s book provides a thorough review of vascular neurology, all presented
through a series of quickly digested real-life cases. Each case illustrates a common
stroke-related diagnostic or treatment situation, and provides insight into the
approach of an experienced clinician. The rationale for decision-making is fully jus-
tified by the available evidence base where data exist, and by sophisticated reasoning
in the gray areas where there are no data. Novices will appreciate the fundamentals
of stroke neurology, but even experts will find new tidbits of information in this
easy-to-read but comprehensive book.”
—Mitchell S. V. Elkind, MD, MS, FAAN, FAHA, Fellowships Director,
Department of Neurology, Columbia University, New York, NY
Lawrence C. Newman, MD
Director of the Headache Institute
Department of Neurology
St. Luke’s Hospital Center
New York, New York
Morris Levin, MD
Professor of Neurology and Psychiatry
Geisel School of Medicine at Dartmouth
Lebanon, NH
Ji Y. Chong, MD
Director, Stroke Prevention Program
St. Luke’s Roosevelt Hospital
Assistant Clinical Professor of Neurology
Columbia University
New York
3
1
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Dedicated to my patients, who continue to teach me about resilience
and determination. Bud Rowland, who taught me so much about
neurology, writing, and thinking, and to “never appeal to authority.”
Hwa and Hyun Chong; Bonnie and David Cantor; Kevin, Sam, and
Andrew Noah Cantor, for their constant support.
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Preface
Nearly 800,000 people have a stroke each year in the United States. On
average, this means someone has a stroke every 40 seconds. Stroke is the
leading cause of disability in this country. These numbers add up to a huge
public health problem that needs to be tackled from all directions: preven-
tion of first stroke, diagnosis and acute treatment of stroke, and prevention
of recurrent strokes.
Neurologists, and specifically vascular neurologists, are the specialists
who primarily treat patients with cerebrovascular disease. But the sheer
number of patients with stroke, as well as the multiple risk factors for
stroke, guarantee that physicians of all disciplines will see a stroke patient.
Although a couple of unusual cases are presented, most of this book deals
with common, practical questions clinicians will encounter. Case presenta-
tions will highlight evidence-based practice. There are clinical trial data to
support many recommendations, but there are also areas in cerebrovascular
disease treatment that are still uncertain. Usual practice in the absence of
strong data will be noted as such.
Cerebrovascular disease is an exciting and evolving field. Many new ther-
apies and risk factors are being investigated, and there is much promise for
significant advances in the coming years.
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Contents
x CONTENTS
16 Secondary Stroke Prevention After Cryptogenic Stroke with Patent
Foramen Ovale (PFO) 69
The presence of a PFO is associated with cryptogenic stroke, especially in young
patients. Medical therapy for patients with stroke and PFO include antiplatelet
therapy or anticoagulation. PFO closure is not routinely recommended for stroke
prevention.
17 Carotid Dissection 73
Carotid dissection should be considered as a stroke etiology, especially in
young patients with a history of trauma. Carotid dissection can be recognized
by exam findings and radiographic studies. Treatment can include aspirin or
anticoagulation.
18 Stroke in a Young Adult 79
Traditional vascular risk factors can contribute to stroke in young adults. In the
absence of typical risk factors in a young patient, a more extensive evaluation
is needed. Other more unusual causes of stroke can include autoimmune,
infectious, hematological, and toxic etiologies.
20 Migrainous Stroke 89
Migraine may mimic stroke, but acute migraine can also be a (rare) cause of stroke.
Since this is a diagnosis of exclusion, other etiologies of stroke need to be investigated.
CONTENTS xi
25 Hypertensive Intracerebral Hemorrhage 109
Hemorrhagic stroke is associated with high morbidity and mortality. A common
cause of ICH is hypertension. Hemorrhage due to hypertension usually occurs in
subcortical locations. Prevention involves aggressive blood pressure control.
Index 139
xii CONTENTS
1 Intravenous Tissue
Plasminogen Activator
(IV tPA) Treatment for Acute
Ischemic Stroke
Her INR and platelet count are normal. It is now 7:00 AM.
A 58-year-old woman with hypertension and diabetes
presents to the emergency room with right hemiparesis.
She had worked her usual night shift and gone home and
had fallen asleep at 3:30 AM. She awoke at 5:30 AM and
noticed right-sided weakness. She called EMS and arrived
in the ER at 6:20 AM. She has a blood pressure of 153/92.
She has normal speech and is without any evidence of
aphasia. She has a right facial droop. She has prominent
weakness of the right arm and leg. Her head CT scan
shows no evidence of hemorrhage or infarct (Figures 1.1,
1.2, 1.3 and 1.4).
1
FIGURES 1.1–1.4 Non-contrast head CT showing basal ganglia calcifications but otherwise
normal findings.
Exclusion
Minor or rapidly improving symptoms
Seizure at onset
Stroke or head trauma within 3 months
Major surgery within 14 days
History of ICH
Aggressive treatment to lower BP<185/110
Subarachnoid hemorrhage (SAH)
Gastrointestinal (GI) or genitourinary (GU) bleeding bleeding within 21 days
Arterial puncture at noncompressible site
Heparin within 48 hours and increased Partial Thromboplastin Time (PTT)
INR >1.7
Platelets <100,000
Glucose <50 or >400
placebo and 52% with tPA in the extended window, thus showing a ben-
efit even out to 4.5 hours. The biggest concern with IV tPA is brain hemor-
rhage risk. In ECASS 3, the symptomatic intracerebral hemorrhage (ICH)
rate was higher in the tPA group than in placebo, but it was comparable
to rates in patients treated within 3 hours. Overall, tPA appears beneficial
and without significant additional risk of ICH out to 4.5 hours. Although
it is not FDA-approved in the extended time window, the American Heart
Association and other societies have recommended tPA use to 4.5 hours
in select patients.
Post-tPA, blood pressure must be monitored and treated carefully,
with a goal BP<180/105. Patients cannot receive any antiplatelet or
KEY POINTS
Bibliography
Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of
adults with ischemic stroke: a guideline from the American Heart Association/
American Stroke Association Stroke Council. Stroke. 2007;38:1655–1711.
Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment:
pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet.
2004;363:786–774.
del Zoppo GJ, Saver JL, Jauch EC, Adams HP. Expansion of the time window for
treatment of acute ischemic stroke with intravenous tissue plasminogen activator:
a science advisory from the American Heart Association/American Stroke
Association. Stroke. 2009;40:2945–2948.
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with
alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–
1329.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.
Tissue plasminogen activator for acute ischemic. N Engl J Med. 1995 ;333:1581–1587.
7
T his patient is exhibiting signs of a left middle cerebral artery (MCA)
occlusion. He has aphasia and right-sided weakness. He just had
coronary bypass surgery so is not eligible for IV tPA. The options for
treatment include intra-arterial (IA) thrombolysis, mechanical clot retrieval,
and medical therapy. There are data supporting all options.
The Prolyse in Acute Cerebral Thromboembolism Trial (PROACT) was
a large randomized trial evaluating the benefit of intra-arterial prouroki-
nase (proUK) in patients with MCA stroke treated within six hours. In
this trial, patients with MCA occlusion were taken for an angiogram and
randomized to intra-arterial infusion at the site of the clot with proUK
with heparin, versus heparin alone. Patients had inclusion and exclusion
criteria similar to those of the NINDS tPA trial, but there was an NIHSS
cutoff of 4 to 30. Forty percent of patients with IA proUK (vs. 25% of
controls) achieved a good outcome. Ten percent of patients in the treat-
ment arm (vs. 2% of controls) had symptomatic ICH. These results were
favorable for treatment, but a second randomized trial has not been done.
Therefore, this treatment is not FDA-approved. But based on the strength
of this trial and other, smaller studies, the American Heart Association
(AHA) recommends intra-arterial tPA within six hours as an option for
select patients with MCA occlusion, especially patients not eligible for
IV tPA.
Several device studies have been completed or are under way. The goal of
these trials was to determine effectiveness of mechanical thrombectomy in
removing clots in patients with ischemic stroke due to a large-artery occlu-
sion. Rather than infuse a lytic drug into a clot, various devices have been
studied to remove the clot. The Mechanical Embolus Removal in Cerebral
Ischemia (MERCI) study evaluated a corkscrew-like device that is deployed
into a clot. Once the clot is engaged, the device along with the clot is pulled
out to restore blood flow. The MERCI study, as well as subsequent studies
using this device, was not a randomized clinical trial. They evaluated rates of
recanalization compared with historic controls. They found recanalization
was associated with better outcomes.
Another study used the Penumbra device, a suction method to extract
clots. This was also a single-arm, non-randomized study. Solitaire With the
Intention For Thrombectomy Trial (SWIFT), the most recent trial, used a
stent-retriever device in which a stent is deployed into the site of occlusion
FIGURE 2.1 Cerebral angiogram showing left upper division MCA occlusion.
FIGURE 2.2 Complete recanalization of the occluded MCA branch after intra-arterial tPA.
Bibliography
Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of
adults with ischemic stroke: a guideline from the American Heart Association/
American Stroke Association Stroke Council. Stroke. 2007;38:1655–1711.
Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic
stroke: the PROACT II study: a randomized controlled trial: Prolyse in Acute
Cerebral Thromboembolism. JAMA. 1999;282:2003–2011.
Penumbra Pivotal Stroke Trial Investigators. The Penumbra pivotal stroke trial: safety
and effectiveness of a new generation of mechanical devices for clot removal in
intracranial large vessel occlusive disease. Stroke. 2009;40:2761–2768.
Saver JL, Jahan R, Levy E, et al. Solitaire flow restoration device versus the MERCI
Retriever in patients with acute ischaemic stroke (SWIFT): a randomized
parallel-group, non-inferiority trial. Lancet. 2012;380:1241–1249.
Smith WS, Sung G, Saver J, et al. Mechanical thrombectomy for acute ischemic stroke:
final results of the Multi MERCI trial. Stroke. 2008;39:1205–1212.
Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in
acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36:1432–1438.
13
T his patient also has a LMCA syndrome. Her head CT shows a dense
LMCA. Her initial event was suggestive of LMCA occlusion with
right-sided weakness. But she may have had reasonable collateral flow
maintaining perfusion to the cortex, initially sparing her language. However,
in order to administer IV tPA, we needed to lower the blood pressure.
FIGURES 3.1–3.4 Noncontrast head CT showing a hyperdensity in the left Sylvian fissure
consistent with a dense left MCA sign.
FIGURE 3.5 Cerebral angiogram A-P view showing left MCA stem occlusion.
KEY POINTS
21
T he most feared complication of IV tPA is intracerebral hemorrhage.
Asymptomatic hemorrhage can occur even without tPA. Hemor-
rhage within already infarcted tissue may not cause any symptoms.
Hemorrhagic transformation is more commonly seen in strokes due to
cardiac embolus.
FIGURE 4.1 Non-contrast head CT prior to IV tPA showing no hemorrhage but a basal ganglia
calcification.
FIGURE 4.2 Non-contrast head CT 24 hours post-tPA showing left MCA and ACA territory
infarct with hemorrhagic transformation.
Bibliography
Alshekhlee A, Mohammadi A, Mehta S, et al. Is thrombolysis safe in the elderly? Analysis
of a national database. Stroke. 2010;41:2259–2264.
Goldstein JN, Marrero M, Masrur S, et al. Management of thrombolysis-associated
symptomatic intracerebral hemorrhage. Arch Neurol. 2010;67:965–969.
Menon BK, Saver JL, Prabhakaran S, et al. Risk score for intracranial hemorrhage
in patients with acute ischemic stroke treated with intravenous tissue type
plasminogen activator. Stroke. 2012;43:2293–2299.
25
M igraine may be a stroke mimic. In the acute setting, there is little time
to complete a full evaluation and wait for resolution of symptoms if
tPA is being considered. Therefore, risks and benefits need to be carefully
reviewed and discussed with the patient. Hemorrhage rates from tPA
increase with higher NIHSS scores, since patients with larger strokes are
more likely to bleed with tPA. Conversely, patients with stroke mimics are
unlikely to have spontaneous ICH, since there is no brain infarct.
In one series of 512 patients treated with IV tPA, 14% were thought
to have a stroke mimic. The most common diagnoses for these patients
were seizure, migraine, and conversion disorder. None had hemorrhagic
complications with tPA.
This patient had a history of migraine, and she developed a focal motor
deficit in the setting of a migraine attack. On one hand, her young age and
history of migraine made complicated migraine a possibility. However, she
had reported a prior history of stroke. She also had hypertension. These
factors would increase the risk of recurrent stroke. Furthermore, she had
never had motor deficit with migraine before. Therefore, waiting to see if
symptoms improved to make a diagnosis of migraine would remove the
possibility of treatment, if this were indeed stroke.
The benefits outweighed the risks of treatment for this patient, and she
was given IV tPA. Her symptoms persisted for three days, then resolved. Her
MRI was subsequently normal and showed no evidence of recent stroke.
This patient was given the diagnosis of complicated migraine and treated
with migraine prophylaxis after a complete workup.
KEY POINTS
■ Patients with stroke mimics are likely to have a low risk for ICH.
■ The benefits outweigh the risks of treatment, since the diagnosis
of a stroke mimic typically occurs after the tPA window closes.
Bibliography
Chernyshev OY, Martin-Schild S, Albright KC, et al. Safety of tPA in stroke mimics and
neuroimaging-negative cerebral ischemia. Neurology. 2010;74:1340–1345.
27
O ften, patients with stroke who have rapidly improving symptoms do
not receive IV tPA. Similarly, patients with minor syndromes also do
not receive treatment. In the NINDS trial, patients were excluded from the
study with the following minor symptoms: pure sensory syndrome, isolated
dysarthria, isolated facial weakness, and isolated monoparesis with only
minor weakness.
Because these patients were excluded from the trial, one of the con-
traindications for tPA is mild or rapidly improving symptoms. However,
studies of patients who were not treated with IV tPA because of rapid
improvement or minor symptoms found these patients had worse out-
comes at discharge. In one study evaluating outcomes in 41 patients
who were deemed “too good to treat,” 27% died or were not able to
be discharged home because of worsening. They also found that patients
who had over 4-point improvement on the NIHSS were more likely
to have subsequent worsening. This is consistent with clinical observa-
tion that rapid improvement is often a more ominous sign than static
symptoms. Rapid improvement implies a dynamic state and is often fol-
lowed by worsening. If worsening occurs outside the IV tPA window, the
patient has lost his opportunity for treatment. Furthermore, as discussed
above, greater stroke severity is associated with greater hemorrhage rates.
Therefore, patients with minor syndromes should also be relatively safe to
treat from a hemorrhage standpoint.
FIGURES 6.1–6.4 MRI diffusion-weighted sequence showing small punctate infarcts in the left
frontal cortex.
This patient was young and worked as an engineer. Hand weakness would
have been disabling for him. For these reasons, this patient was treated with IV
tPA at 1 hour 55 minutes. His MRI showed two small punctate infarcts, with
one in the hand region of the motor cortex (Figures 6.1, 6.2, 6.3 and 6.4).
KEY POINTS
Bibliography
Rajajee V, Kidwell C, Starkman S, et al. Early MRI and outcomes of untreated patients
with mild or improving ischemic stroke. Neurology. 2006;67:980.
Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive
intravenous tissue plasminogen activator because of mild or improving ischemic
stroke. Stroke. 2005;36:2497–2499.
31
FIGURE 7.1 CT scan showing infarction of the complete RMCA territory with edema causing
compression of the right lateral ventricle and shift of midline structures to the left.
FIGURE 7.2 CT scan showing right hemicraniectomy with alleviation of mass effect on the
hemisphere.
Bibliography
Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute
ischaemic stroke. Cochrane Database Syst Rev. 2012 Jan 18;1:CD003435.
Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. “Malignant”
middle cerebral artery territory infarction: clinical course and prognostic signs.
Arch Neurol. 1996;53:309–315.
Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al; DECIMAL, DESTINY,
and HAMLET investigators. Early decompressive surgery in malignant infarction of
the middle cerebral artery: a pooled analysis of three randomised controlled trials.
Lancet Neurol. 2007;6:215–222.
35
FIGURES 8.1–8.2 MRI diffusion-weighted sequence showing large right cerebellar stroke.
FIGURES 8.3–8.6 CT scan showing mass effect on the fourth ventricle and new obstructive
hydrocephalus.
KEY POINTS
39
B lood pressure and mortality after a stroke follow a J-shaped curve
with significantly low and high blood pressures associated with higher
mortality. Blood pressure is commonly elevated after a stroke, and there is
often an immediate impulse to treat the blood pressure. However, there
are several theoretical reasons to not treat. Cerebral autoregulation allows
for tight control of cerebral perfusion pressure over a wide range of mean
arterial pressures. However, the ischemic brain no longer has autoregulatory
capacity, and the cerebral perfusion pressure (CPP) is linearly dependent on
mean arterial pressure (MAP). Therefore, abrupt lowering of blood pressure
may expand the ischemic penumbra. Positron emission tomography (PET)
studies support this.
However, sustained high blood pressure is also associated with increased
mortality. Possible mechanisms may be increased edema or increased risk of
hemorrhage with elevated blood pressure.
In a small randomized trial, the investigators found early lowering
of blood pressure with labetolol or lisinopril, compared with placebo,
within 36 hours after stroke onset was associated with better outcomes
with treatment. Treated patients had SBP decrease of 21 mmHg, versus
11 in placebo. They found no early neurological deterioration, but there
was improved three-month mortality (9.7% vs. 20.3%). However, a much
larger randomized trial that included over 2,000 subjects did not find ben-
efit in acutely lowering blood pressure. This trial used candesartan ver-
sus placebo in ischemic or hemorrhagic stroke treated within 30 hours of
stroke onset. The mean difference in BP was 5/2 mmHg. There was no
benefit for early treatment, and in fact, there was a trend toward worse
functional outcome.
The AHA recommends treatment for SBP over 220 or diastolic blood
pressure (DBP) over 120. If treatment is warranted, the blood pressure should
be lowered cautiously, 15% to 20% in the first 24 hours. A short-acting,
easily titratable drug is preferred. Blood pressure often drops spontaneously
within the first 24 hours without any intervention. Certainly, if there is
evidence of end organ damage such as acute myocardial infarction (MI),
congestive heart failure (CHF), renal failure, hypertensive encephalopathy,
or retinopathy, early treatment may need to be instituted.
KEY POINTS
Bibliography
Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of
adults with ischemic stroke: a guideline from the American Heart Association/
American Stroke Association Stroke Council. Stroke. 2007;38:1655–1711.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): A
randomized trial of aspirin, subcutaneous heparin, both, or neither among 19435
patients with acute ischaemic stroke. Lancet. 1997;349:1569–1581.
Potter JF, Robinson TG, Ford GA, et al. Controlling hypertension and hypotension
immediately post-stroke (CHHIPS): a randomized, placebo-controlled, double-blind
trial. Lancet Neurol. 2009;8:48–56.
Sandset EC, Bath PM, Boysen G, et al.; SCAST Study Group. The angiotensin-receptor
blocker candesartan for treatment of acute stroke (SCAST): a randomised,
placebo-controlled, double-blind trial. Lancet. 2011 Feb 26;377(9767):741–750.
43
FIGURES 10.1–10.2 MRI FLAIR with white matter hyperintensities.
KEY POINTS
49
I n a patient with asymptomatic carotid stenosis, one of the questions is
whether revascularization is warranted. This is followed by what type of
revascularization should be considered. There are two large randomized
trials of carotid endarterectomy (CEA) versus medical therapy for stroke
prevention that support the use of CEA. In Asymptomatic Carotid
Atherosclerosis Study (ACAS), the angiographic criterion of >60% stenosis
was used. They found the five-year risk of ipsilateral stroke, perioperative
stroke, or death to be 5.1% with surgery, versus 11% with medical therapy.
The other trial, Asymptomatic Carotid Surgery Trial (ACST), included
Doppler criteria of 70% stenosis for enrollment. They found the five-year
risk of perioperative stroke, MI, death, or non-perioperative stroke to be
6.4% versus 11.8%. A follow-up study at 10 years showed the stroke risk to
be 10.8% in the CEA arm, versus 16.9% in the medical arm.
Overall, there appears to be a benefit of CEA in patients with asymp-
tomatic stenosis. But patients need to be selected very carefully. Subgroup
analysis suggests women may not benefit as much from CEA. Age also plays
a role, since the number of patients over age 75 in trials of surgery is too few
to establish its efficacy in older people. Life expectancy must be considered,
since there is an up-front risk of perioperative stroke and death before a
benefit may be realized. Choice of operator is also important. Any perioper-
ative complication rates greater than the 2.3% for stroke or death reported
in the ACAS trial could eliminate the potential benefit of the operation.
The other treatment option is angioplasty and stenting of the carotid
stenosis. The Carotid Revascularization Endarterectomy versus Stenting Trial
(CREST) was a randomized trial of symptomatic and asymptomatic patients
with carotid stenosis comparing stenting to CEA. In the asymptomatic patients,
stenosis was >60% by angiography or >70% by ultrasound. The primary out-
come was periprocedural stroke, death, or MI and ipsilateral stroke up to four
years of follow-up. They found no significant difference in outcomes (7.2%
CAS vs. 6.8% CEA). Perioperatively, stroke was more likely with CAS (4.1%
vs. 2.3%) and MI more likely after CEA (2.3% vs. 1.1%). Patients younger
than 70 did better with CAS, and those older than 70 did better with CEA.
These studies overall suggest a modest benefit to revascularization in pre-
venting stroke. However, medical therapy has improved over the years, with
better blood pressure control and wider use of statins. The benefit of CEA
or stent versus current aggressive medical therapy is not known. Patients
should be selected very carefully for revascularization, and its risks and ben-
efits explained as discussed above.
This patient was young. He had been on good medical therapy after his
coronary bypass surgery and yet had significant progression of carotid dis-
ease. He also had coronary disease and multiple medical problems placing
him at higher risk for surgery. Given his age less than 70 and his comorbidi-
ties, he had a stent placed (Figures 11.1 and 11.2), without any periopera-
tive complications.
Bibliography
Brott TG, Hobson RW, Howard G, et al. Stenting versus endarterectomy for treatment of
carotid artery stenosis. N Engl J Med. 2010;363:11–23.
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
Endarterectomy for asymptomatic carotid artery stenosis. JAMA.
1995;273:1421–1428.
Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid
endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomized
trial. Lancet. 2010;376:1074–1084.
MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention
of disabling and fatal strokes by successful carotid endarterectomy in patients
without recent neurological symptoms: randomized controlled trial. Lancet.
2004;363:1491–1502.
53
L acunar strokes make up about 25% of all ischemic strokes. Lacunes are
caused by infarction of a small penetrator vessel. There are classic lacunar
syndromes: pure motor, pure sensory, sensorimotor, ataxic hemiparesis,
and clumsy-hand dysarthria. The sensitivity and specificity of these clinical
findings and a lacunar stroke are not one hundred percent, and a workup is
certainly needed to exclude large-vessel disease or a cardiac source of emboli.
The imaging finding of a small, deep infarct in the absence of other possible
etiologies is suggestive of a lacune. Lacunar strokes are strongly associated
with hypertension.
In this patient, a secondary stroke prevention strategy would need to
include aggressive blood pressure monitoring and treatment. Several studies
have shown that reduction in blood pressure significantly lowers recurrent
stroke risk. Although blood pressure targets need to be individualized based
on patients’ comorbidities, normotension is now defined as 120/80. The
choice of antihypertensives also needs to be individualized. The combina-
tion of diuretic and ACE inhibitor has been shown to be beneficial.
Statins are also important in secondary stroke prevention. The SPARCL
trial randomized patients with stroke or TIA but no coronary disease to
atorvastatin 80 mg versus placebo. Patients treated with atorvastatin had
lower rates of recurrent stroke and cardiac events. There did appear to be a
trend toward more hemorrhagic strokes.
Patients with lacunar strokes should also be on an antiplatelet agent.
Three medications may be used as first line of defense: aspirin, aspirin with
extended-release dipyridamole, and clopidogrel. There are minor differences
in efficacy, so choice of drug is also tailored to the patient. ASA is once a
day and is usually well tolerated. For chronic secondary stroke prevention,
doses of 50 mg to 1500 mg appear equivalent; however, there is greater gas-
trointestinal bleeding rates with higher doses. The typical dose prescribed
is 81 mg or 325 mg. The combination of aspirin with extended-release
dipyridamole when compared with ASA has a small benefit in secondary
stroke prevention. However, headache and gastrointestinal (GI) symp-
toms were more common. Clopidogrel and aspirin with extended-release
dipyridamole had similar efficacy in the Prevention Regimen for Effectively
avoiding Second Strokes (PROFESS) trial. Clopidogrel may have interac-
tions with proton pump inhibitors (PPI), which may increase the risk of
cardiovascular events. There are also genetic variants in hepatic metabolism
KEY POINTS
Bibliography
Amarenco P, Bogousslavsky J, Callahan A III., et al. High-dose atorvastatin after stroke or
transient ischemic attack. N Engl J Med. 2006;355:549–559.
Benavente OR, Hart RG, McClure LA, et al. Effects of clopidogrel added to aspirin in
patients with recent lacunar stroke. N Engl J Med. 2012;367:817–825.
57
FIGURE 13.1 MRI diffusion-weighted image showing right temporal and insular infarct.
KEY POINTS
Bibliography
Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients
with symptomatic moderate or severe stenosis. North American Symptomatic
Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998;339:1415–1425.
Brott TG, Halperin JL, Abbara S, et al. ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/
SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with
extracranial carotid and vertebral artery disease: executive summary. Stroke.
2011;42:e420–e463.
Brott TG, Hobson RW, Howard G, et al. Stenting versus endarterectomy for treatment of
carotid artery stenosis. N Engl J Med. 2010;363:11–23.
Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with
symptomatic severe carotid stenosis. N Engl J Med. 2006;355:1660–1671.
Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ. Endarterectomy for
symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.
Lancet. 2004;363:915–924.
61
FIGURE 14.1 MRI diffusion-weighted imaging showing patchy left MCA infarcts.
FIGURE 14.2 CT angiography showing irregularity and stenosis of the left MCA.
KEY POINTS
Bibliography
Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy
for intracranial arterial stenosis. N Engl J Med. 2011;365:993–1003.
Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for
symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352:1305–1316.
14 INTRACRANIAL ATHEROSCLEROSIS 63
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15 Secondary Stroke Prevention
After Cardioembolic Stroke
65
A trial fibrillation is a potent risk factor for stroke. The CHADS2 score
is often used to risk stratify patients to determine treatment.
CHADS2:
C–CHF 1
H–Hypertension 1
A–Age > 75 1
D–Diabetes 1
S2–Stroke, TIA, or prior embolism 2
FIGURE 15.2 Gradient echo sequence with hypointensity consistent with hemorrhagic
transformation.
KEY POINTS
Bibliography
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigitran versus warfarin in patients with
atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139–1151.
Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N
Engl J Med. 2011;364:806–817.
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with
atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981–992.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial
fibrillation. N Engl J Med. 2011 Sep 8;365(10):883–891.
69
T his is a patient who had a stroke, and an extensive evaluation did not
reveal a large-artery or obvious cardiac source of emboli. The infarct
was not a lacune. An embolic-appearing stroke without an obvious source
would be classified as cryptogenic. About 30% of strokes are categorized
as cryptogenic, but in patients under age 55, 40% may be cryptogenic.
Several studies have suggested an association between PFO, or PFO and
atrial septal aneurysm, and cryptogenic stroke.
A patent foramen ovale is a persistent communication between the two
atria of the heart. This communication typically closes after birth, but in
about 20% of people, it remains open as a PFO. One possible mechanism
for stroke from PFO is a paradoxical embolus, in which a venous clot can
traverse the PFO and enter the arterial circulation to the brain. Although
studies have found an association between PFO and stroke, it does not
appear to confer additional risk of recurrent stroke compared with crypto-
genic stroke without PFO if the patient is on medical therapy.
The ideal medical therapy is not entirely clear. A subset of a larger ran-
domized trial of warfarin versus ASA in stroke evaluated patients with cryp-
togenic stroke and PFO. In the PFO in Cryptogenic Stroke Study (PICSS)
sub-study, there was no difference in recurrent stroke rates between patients
on ASA versus those on warfarin. However, this patient population was
older and had more vascular risk factors than other studies of patients with
cryptogenic stroke. The PFO may not have been a significant contributor
to stroke risk, so the results of this study may not apply to young patients
with PFO and no other vascular risk factors.
PFO closure has also been considered in patients with cryptogenic
stroke. The CLOSURE trial used a percutaneous occlusive device to close
PFOs. In this study, the two-year stroke rate was 2.9% in the closure arm,
compared with 3.1% in the medical arm; there was no statistically signifi-
cant difference. The medical arm received either ASA, warfarin, or both, at
the investigator’s discretion. The patients treated with PFO closure had a
higher incidence of post-procedure atrial fibrillation. Given the potential
complications and no clear benefit, PFO closure is not routinely recom-
mended for secondary stroke prevention.
Other studies using longer-duration cardiac monitoring suggest that there
is a higher rate of paroxysmal atrial fibrillation in patients with cryptogenic
KEY POINTS
Bibliography
Bogousslavsky J, Garazi S, Jeanrenaud X, et al. Stroke recurrence in patients with patent
foramen ovale: the Lausanne Study. Neurology. 1996;46:1301–1305.
Furlan AJ, Meisman M, Massaro J, et al. Closure or medical therapy for cryptogenic
stroke with patent foramen ovale. N Engl J Med. 2012;366:991–999.
Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients
with patent foramen ovale: Patent foramen ovale in Cryptogenic Stroke Study.
Circulation. 2002;105:2625–2631.
Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen
ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic
attack. Am Heart J. 1995;130:1083–1088.
Messe SR, Silverman IE, Kizer JR, et al. Practice parameter: Recurrent stroke
with patent foramen ovale and atrial septal aneurysm: Report of the Quality
Standards Subcommittee of the American Academy of Neurology. Neurology.
2004;62:1042–1050.
73
FIGURE 17.1 CT scan showing dense left MCA sign, and CT angiogram showing occlusion of
the left ICA.
FIGURE 17.2 Angiogram showing tapering occlusion of the left ICA. Mechanical thrombectomy
of the distal ICA allowed for cross-filling from the right.
17 CAROTID DISSECTION 75
FIGURE 17.3 MRI with patchy left MCA infarct.
FIGURE 17.4 MRA showing persistent occlusion of the left ICA but robust collateral flow to the
LMCA from the anterior communicating artery.
Bibliography
Kremer C, Mosso M, Georgiadis D, et al. Carotid dissection with permanent and transient
occlusion or severe stenosis: Long term outcome. Neurology. 2003;60:271–275.
Patel R, Adam R, Maldjian C, et al. Cervical carotid artery dissection: Current review of
diagnosis and treatment. Cardiol in Rev. 2012;20:145–152.
Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med.
2001;344:898–906.
17 CAROTID DISSECTION 77
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18 Stroke in a Young Adult
79
FIGURES 18.1–18.2 MRI DWI sequence showing recent bilateral infarcts in the temporal and
parietal lobes.
This patient was young and had no significant risk factors for stroke.
Her initial workup included evaluation for more typical causes of stroke.
Her TEE was normal. She had an angiogram that showed no evidence of
large-vessel vasculopathy. The key laboratory findings were the low platelets
and anemia. A peripheral smear confirmed hemolytic anemia, and she was
diagnosed with thrombotic thrombocytopenic purpura (TTP), a rare cause
of stroke. She was treated with plasma exchange.
Bibliography
Ferro JM, Massaro AR, Mas JL. Aetiological diagnosis of ischaemic stroke in young
adults. Lancet Neurol. 2010;9:1085–1096.
Larrue V, Berhoune N, Massabuau P. et al. Etiologic investigation of ischemic stroke in
young adults. Neurology. 2011;76:1983–1988.
83
FIGURES 19.1–19.4 CT with small parasagittal intraparenchymal hemorrhage and small
subarachnoid hemorrhage.
FIGURE 19.5 CTA coronal view showing small left ACA aneurysm.
Because this patient had a hemorrhage and she would eventually need
to resume anticoagulation for her mechanical heart valves, she was taken
for treatment with embolization (Figures 19.7 and 19.8). Her warfarin
was held for one week, then resumed after embolization. She continued IV
antibiotics for six weeks. A repeat angiogram at the end of her antibiotic
course showed no new lesions.
KEY POINTS
Bibliography
Heiro M, Nikoskelainen J, Engblom E, et al. Neurological manifestations of infective
endocarditis: a 17-year experience in a teaching hospital in Finland. Arch Intern Med.
2000;160:2781–2787.
Peters PJ, Harrison T, Lennox JL. A dangerous dilemma: management of
infectious intracranial aneurysms complicating endocarditis. Lancet Infect Dis.
2006;6:742–748.
89
FIGURE 20.1 MRI DWI with evidence of infarct along the right lateral ventricle.
T his patient is having a migraine but has a new focal neurological deficit.
As discussed in a prior chapter, migraine may be a stroke mimic, but
migraine may also be a risk factor for stroke. There are many proposed
mechanisms linking migraine to stroke: recurrent vasodilation may lead to
impaired cerebral autoregulation; endothelial change can occur; increased
inflammation can cause increased platelet reactivity. Migraine has been
associated with stroke in young people.
Acute migraine can also directly cause stroke. The International Headache
Society (IHS) defines migrainous stroke as a typical attack of migraine with
aura, not reversible in seven days, and with evidence of infarct on imaging.
A study of patients with stroke in the setting of migraine included patients
with migraine with or without aura, presenting with acute migraine and
neurological symptoms, and who were found to have acute infarct on MRI
DWI. The majority (70%) had DWI lesions in the posterior circulation.
Almost all (94%) had at least one other risk factor for stroke, especially
hypertension. The exact mechanism of migraine directly causing stroke is
unknown, but it is speculated that sustained oligemia or vasospasm with
thrombosis during aura plays a role.
Migrainous stroke would be a diagnosis of exclusion. This patient had a
full evaluation of his vessels and heart. He had no evidence of a large artery
or cardiac source of his stroke. He had no hematological abnormalities.
KEY POINTS
Bibliography
Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with
migraine: systematic review and meta-analysis of observational studies. BMJ.
2005;330:63.
Kruit MC, van Buchem MA, Hofman PA, et al. Migraine as a risk factor for subclinical brain
lesions. JAMA. 2004;291:427–434.
Stang PE, Carson AP, Rose KM, et al. Headache, cerebrovascular symptoms, and stroke:
The Atherosclerosis Risk in Communities Study. Neurology. 2005;64:1573–1577.
Swartz RH, Kern RZ. Migraine is associated with magnetic resonance imaging white
matter abnormalities. Arch Neurol. 2004;61:1366–1368.
20 MIGRAINOUS STROKE 91
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21 Dural Venous Sinus
Thrombosis
93
FIGURE 21.1 CT showing hyperdensity along the right transverse sinus.
FIGURE 21.2 Right sylvian subarachnoid blood and hyperdensity in the superior sagittal sinus.
KEY POINTS
Bibliography
Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral
vein and dural sinus thrombosis: results of the International Study on Cerebral Vein
and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35:664–670.
Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005;352:1791–1798.
97
FIGURE 22.1 MRI with bilateral chronic infarcts in a distal ICA territory.
T his patient was having recurrent TIAs. Her pattern of infarcts on MRI is
suggestive of distal ICA watershed infarcts. Her MRA showed bilateral
distal ICA occlusions. This was confirmed by angiography. In a young patient
with bilateral ICA occlusive disease, Moyamoya disease should be considered.
This type of occlusive disease is not consistent with CNS vasculitis.
Moyamoya is a disease in which there is bilateral stenosis or occlusion
of the terminal portion of the ICAs. An abnormal vascular network of col-
lateral blood vessels develops at the base of the brain that has an angio-
graphic appearance of a puff of smoke. There is a higher prevalence in Asian
populations, but it can be seen in other race/ethnic groups. Moyamoya
has been associated with cranial radiation, Down’s syndrome, and sickle
cell disease. Pathologically, the vessels appear to develop intimal thickening
with smooth-muscle proliferation.
Patients may present with stroke or hemorrhage, with hemorrhage more
common in adults and rarer in children. Headaches and seizures may also
occur. Medically, patients are usually treated with antiplatelet therapy to
reduce the risk of stroke from thrombi at areas of stenoses. Anticoagulation
is not used, especially since there is a risk of ICH from rupture of friable
collateral vessels.
There are no clinical trials to assess different treatments, but different revas-
cularization techniques have been used, mostly in children. There appears
to be benefit with surgical treatment, but there are limited data in adults.
Since the disease is limited to intracranial vessels, the goal is to redirect exter-
nal carotid artery branches to supply the ischemic brain. Direct bypass can
be done with a superficial temporal artery to MCA bypass allowing diver-
sion of extracranial blood to the intracranial circulation. This allows for rapid
FIGURE 22.3 Cerebral angiogram showing occlusion of the ICA and prominent lenticulostriate
vessels.
22 MOYAMOYA DISEASE 99
restoration of blood flow. Indirect bypass with encephaloduroarteriosynan-
giosis (EDAS) allows for ECA branches to develop collateral flow to the isch-
emic brain over time.
In this patient, hemodynamic studies confirmed flow failure. She ini-
tially had a right-sided EDAS followed two months later by left EDAS. She
had no recurrent strokes.
KEY POINTS
Bibliography
Pandey P, Steinberg GK. Neurosurgical advances in the treatment of Moyamoya disease.
Stroke. 2011;42:3304–3310.
Scott RM, Smith ER. Moyamoya disease and Moyamoya syndrome. N Engl J Med.
2009;360:1226–1237.
101
FIGURES 23.1–23.2 MRI FLAIR showing hyperintensities in sulci consistent with subarachnoid
hemorrhage.
Bibliography
Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction
syndromes: Analysis of 139 cases. Arch Neurol. 2011;68:1005–1012.
105
T his patient had a TIA. He had acute neurological symptoms that fit
a vascular territory. The definition of TIA has been evolving. The
traditional definition was time-based, and symptoms had to resolve within
24 hours. The 24-hour time limit was arbitrary and certainly did not fit
with timing of irreversible brain infarction. A newer definition includes a
shorter duration of symptoms and includes imaging. This definition of TIA
is: symptoms typically last less than an hour, and there is no evidence of
infarct on imaging. There have been attempts at risk-stratification of TIA
patients. The ABCD2 score is commonly used (Table 24.1).
This scale may help identify patients who are at high risk of early recur-
rence. In one study, the risk of recurrent stroke or TIA at 48 hours with
the highest ABCD2 scores was up to 8%. Imaging may also be of use.
Studies have suggested that patients who have clinical resolution of symp-
toms but show evidence of acute infarct on MRI may also be at high risk
of recurrence.
Regardless of score, we generally admit all patients with TIA to expe-
dite a workup. The workup should include brain imaging, vascular imag-
ing, and cardiac evaluation, with at least an EKG and an echocardiogram.
Hospitalization is usually the quickest way to complete an evaluation
and start a prevention program. However, other means of rapid evalu-
ation and treatment, such as a TIA clinic, have been shown to improve
outcomes.
This patient was hospitalized for an evaluation that included an echocar-
diogram and vascular imaging. He was found to have a LMCA stenosis and
was treated with antiplatelets and statin.
Bibliography
Arsava EM, Furie KL, Schwamm LH, et al. Prediction of early stroke risk in transient
symptoms with infarction: relevance to the new tissue based definition. Stroke.
2011;42:2186–2190.
Galvin R, Geraghty C, Motterlini N, et al. Prognostic value of the ABCD2 clinical prediction
rule: a systematic review and meta-analysis. Fam Pract. 2011;28:366–376.
Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of
scores to predict very early stroke risk after transient ischaemic attack. Lancet.
2007;369:283–292.
Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient
ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a
prospective population-based sequential comparison. Lancet. 2007;370:1432–1442.
Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at
high early risk of stroke after a transient ischaemic attack. Lancet. 2005;366:29–36.
109
FIGURE 25.1 Head CT with hyperdensity in the right basal ganglia suggestive of hypertensive ICH.
KEY POINTS
Bibliography
Adeoye O, Broderick JP. Advances in the management of intracerebral hemorrhage. Nat
Rev Neurol. 2010;6:593–601.
Gurol ME, Greenberg SM. Management of intracerebral hemorrhage. Curr Atheroscler
Rep. 2008;10:324–331.
Morgenstern LB, Hemphill JC, Anderson C, et al. Guidelines for the management of
spontaneous intracerebral hemorrhage. A guideline for healthcare professionals
from the American Heart Association/American Stroke association. Stroke. 2010;41.
2108–2129.
113
FIGURE 26.1 CT showing skull defect due to prior craniotomy, encephalomalacia in the right
frontal and temporal lobes, hyperdensity in the left temporal/insular lobes.
KEY POINTS
Bibliography
Mendelow AD, Gregson BA, Fernandes HM, et al.; STICH investigators. Early surgery
versus initial conservative treatment in patients with spontaneous supratentorial
intracerebral haematomas in the International Surgical Trial in Intracerebral
Haemorrhage (STICH): a randomised trial. Lancet. 2005;365(9457):387–397.
Smith EE, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of
the Boston Criteria. Curr Atheroscler Rep. 2003;5:260–266.
Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol.
2011;70:871–880.
117
FIGURE 27.1 CT with hemorrhage in the cerebellar vermis and fourth ventricle.
FIGURE 27.2 Cerebral angiogram showing PCA and PICA feeding arteries to the cerebellar AVM.
KEY POINTS
Bibliography
Ogilvy CS, Stieg PE, Awad I, et al. Special Writing Group of the Stroke Council,
American Stroke Association. AHA Scientific Statement: recommendations for
the management of intracranial arteriovenous malformations: a statement for
healthcare professionals from a special writing group of the Stroke Council. Stroke.
2001;32:1458–1471.
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brain arteriovenous malformation. Neurology. 2006;66:1350–1355.
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malformations: a systematic review and meta-analysis. JAMA. 2011;306:2011–2019.
121
FIGURE 28.1 MRI T2 weighted sequence showing chronic hemosiderin in the right temporal lobe.
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malformations. Curr Atheroscler Rep. 2012;14:360–365.
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cavernous angiomas. J Neurosurg. 1991;75:702–708.
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intracerebral cavernous malformations. Neurology. 2012;78:632–636.
125
FIGURES 29.1–29.4 CT without obvious subarachnoid blood, but hyperdensity along the
tentorium.
FIGURES 29.5–29.8 FLAIR with subtle subarachnoid and subdural blood. 29.8: MRI with
contrast, coronal view showing left posterior communicating artery aneurysm.
KEY POINTS
Bibliography
Connolly ES, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of
aneurysmal subarachnoid hemorrhage. A guideline for healthcare professionals
from the American Heart Association/American Stroke association. Stroke.
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131
FIGURE 30.1 CT scan with subarachnoid hemorrhage in the suprasellar cistern.
KEY POINTS
Bibliography
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subarachnoid hemorrhage in 108 patients. Eur J Neurol. 2012;19:457–461.
Rinkel GJ, Wijdicks EF, Hasan D, et al. Outcome in patients with subarachnoid
hemorrhage and negative angiography according to pattern of hemorrhage on
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135
W ith the widespread use of brain imaging such as MRI and MRA
for symptoms like headache, we are detecting more asymptomatic
intracranial aneurysms. The knowledge that there is 50% mortality with
rupture of an aneurysm provokes much anxiety. Patients naturally want to
know their risk of bleeding and the potential treatments.
In order to decide about any treatment for an intracranial aneurysm that
has not bled, it is important to evaluate the risk of bleeding and weigh that
against the risks and benefit of treatment. The location and size of the aneu-
rysm is important, since both play a significant role in risk of hemorrhage.
The first question in location is whether the aneurysm is intradural or extra-
dural. Cavernous carotid aneurysms are extradural and hence do not cause
subarachnoid hemorrhage when they rupture. They can cause symptoms
due to compression of other structures. Eye movement abnormalities can
be seen due to compression of the third, fourth, and sixth cranial nerves.
Treatment of these aneurysms is usually warranted only if they cause com-
pressive symptoms.
Carotid aneurysms that are intradural cause subarachnoid hemorrhage.
The next level of determining risk is whether the aneurysm is within the
anterior or posterior circulation. Then the size needs to be considered.
The International Study of Unruptured Intracranial Aneurysms (ISUA)
study found that, in patients without a history of prior ruptured aneurysm,
the cumulative risk of SAH in five years was dependent on location and size
(see Table 31.1).
A recent Japanese study also showed a relationship between size and loca-
tion with risk of hemorrhage. They found A comm and P comm aneurysms
more likely to rupture. This study also found morphology of the aneurysm
was important. Aneurysms with a daughter sac were also more likely to
rupture.
From Wiebers D. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks
of surgical and endovascular treatment. Lancet. 2003;362(9378):103–110.
KEY POINTS
139
antiplatelet therapy (cont.) bacterial endocarditis, and mycotic
secondary stroke prevention, 53, 54, 55, 75 aneurysm, 83–87
for transient ischemic attack (TIA), 106 basal gangllia calcifications, 2, 22
to treat Moyamoya disease, 98 beta amyloid deposition, effects of,
apixaban, 68 114
arteriovenous malformation (AVM) Boston Criteria to categorize cerebral
images, 119, 120 amyloid angiopathy, 114
incidence, 118 brainstem, and compression from edema,
and intracerebral hemorrhage (ICH), 32, 37, 38
117–120 “bridging therapy” and recanalization, 16
treatment, 118–119
ASA calcifications, basal ganglia, 2, 22
See aspirin prophylaxis for stroke calcium channel blockers
Asian-Americans after aneurysmal subarachnoid
prevalence of Moyamoya disease, 98 hemorrhage, 128
risk of intracranial atherosclerosis, 62 to treat reversible cerebral
aspirin prophylaxis for stroke vasoconstriction syndrome, 103
and intracranial atherosclerosis, 62–63 Call-Fleming syndrome, 101–104
prevention of secondary stroke cardioembolic stroke
after cryptogenic stroke, 71 incidence in young adults, 80
after dissection, 75, 77 secondary stroke prevention after,
after lacunar stroke, 53, 54, 55 65–68
after migrainous stroke, 91 carotid aneurysms, 136
after thrombosis, 96 carotid dissection, 73–77
primary stroke prevention, 46 carotid endarterectomy
Asymptomatic Carotid Atherosclerosis after stroke due to carotid stenosis, 58
Study (ACAS), 50 and asymptomatic stenosis, 50
asymptomatic intracranial aneurysm, 135–138 perioperative complications, 58–59
complications and likelihood of rupture, Carotid Revascularization Endarterectomy
136 Versus Stenting Trial (CREST), 50, 58
treatment risk and benefit, 137 carotid stenosis, and secondary stroke
asymptomatic stenosis prevention, 57–59
of internal carotid artery (ICA), 49–52 cavernous carotid aneurysms,
angiography, 51 136
angioplasty, 50–51 cavernous malformation
carotid endarterectomy, 50 image suggestive of, 122
medical management of, 50, 51, 52 and intracerebral hemorrhage, 121–123
atorvastatin, 54, 55 cerebellar stroke
atrial fibrillation, and risk for stroke, 66, MRI diffusion-weight sequence showing,
68, 70–71 36, 37
atrial septal aneurysm, and cryptogenic rapid deterioration after, 37
stroke, 70 suboccipital decompression for, 35–38
140 INDEX
cerebral amyloid angiopathy (CAA), 113–115 Down’s syndrome, and Moyamoya
cerebral autoregulation and perfusion disease, 98
pressure, 40 drain, ventriculostomy, 38
cerebral vasoconstriction syndrome, dural venous sinus thrombosis, 93–96
reversible, 101–104 diagnosis, 95–96
cervical carotid artery, dissection in previous images suggestive of, 94
trauma patient, 74 risk factors for, 94–95
CHADS2 score, and stroke risk from atrial treatment, 96
fibrillation, 66, 68
cholesterol, in young adults, 80 ECASS
clopidogrel See European Cooperative Acute Stroke
genetic variants in hepatic metabolism, Study (ECASS)
54–55 edema
secondary stroke prevention, 54, 55, 63 causes and treatment, 32–33
CLOSURE trial, 70 and compression of right lateral
coronary disease, and treating hypertension, 45 ventricle, 32
cortico-subcortical hemorrhages, 114, 115 Ehler-Danlos type IV, 74
cranial radiation, and Moyamoya disease, encephalopathy, and bacterial
98 endocarditis, 84
craniectomy endarterectomy, carotid
hemicraniectomy, 31–34 after stroke due to carotid stenosis, 58
suboccipital craniectomy, 38 and asymptomatic stenosis, 50
CREST perioperative complications, 58–59
See Carotid Revascularization endocarditis, bacterial, 83–87
Endarterectomy Versus Stenting endovascular treatment
Trial (CREST) for acute ischemic stroke, 7–11
cryptogenic stroke, and secondary stroke key points, 11
prevention after, 69–71 options available, 8
epilepsy, and cavernous
dabigitran, 68 malformation, 123
deep vein thrombosis, prevention after etiology of stroke in young adults, 81
ICH, 110–111 European Cooperative Acute Stroke Study
developmental venous anomaly, 123 (ECASS)
diabetes defining symptomatic hemorrhagic
increasing prevalence in young adults, 80 transformation, 23
and secondary stroke prevention, 63, 71 treating acute ischemic stroke with IV
and treating hypertension, 45, 46 tPA, 3, 4, 5
dipyridamole, extended release, 54 exercise, and stroke prevention, 63
dissection extended-release dipyridamole, 54
as cause of stroke in young adults, 80 external ventricular drain (EVD),
of internal carotid artery, 73–77 119
diuretics, 45, 54 extradural vs. intradural aneurysm, 136
INDEX 141
fever, and bacterial endocarditis, 83, 84 predictors of after tPA, 23
fibromuscular dysplasia, and spontaneous secondary to arteriovenous
dissection, 74 malformation (AVM), 117–120
focal stenoses, 103 secondary to cavernous malformation,
Framingham Stroke Profile, 46 121–123
fresh frozen plasma, 110 symptomatic vs. asymptomatic, 23
frontal cortex, punctate infarcts in, perimesencephalic subarachnoid
28, 29 hemorrhage, 131–133
subarachnoid hemorrhage in
glucocorticoids, 103 suprasellar cistern, 132
vs. non-perimesencephalic, 132
head trauma hemorrhagic complications of tPA, 4, 8, 9,
and risk of dural venous sinus 21–24
thrombosis, 95 hemorrhagic transformation
and use of IV tPA, 75 gradient echo sequence, 66
headache and infarcted tissue, 22
migraine, 25–26 post-tPA, 22
“thunderclap headache,” 101, 102, 104, symptomatic vs. asymptomatic, 23
132 usual practice in treating post-tPA, 23
heart valves, and mycotic aneurysm, heparin
83–87 low-molecular-weight, 96
hemicraniectomy subcutaneous, 111
for large MCA stroke, 31–34 hepatic metabolism, genetic variants in,
quality of life after, 33, 34 54–55
scan showing, 33 hormone replacement therapy, 46
hemorrhage Horner’s syndrome, 73, 74, 77
aneurysmal subarachnoid hemorrhage, Hunt Hess grading system for neurological
125–130 deficit, 127, 128
hospitalization and treatment, 128 hydrocephalus, and cerebellar stroke, 37, 38
Hunt Hess grading system for hyperosmolar therapy, and reducing brain
neurological deficit, 127, 128 edema, 32, 33
images, 126, 127 hypertension
morbidity and mortality rates, 126, 130 association with lacunar stroke, 54
in cerebellar vermis and fourth ventricle, association with migrainous stroke, 90
118 increasing prevalence in young adults, 80
hypertensive intracerebral hemorrhage, management in acute stroke, 39–41
109–111 management in stroke prevention
images of, 84 and cryptogenic stroke, 71
intracerebral hemorrhage (ICH) and intracranial atherosclerosis, 63
hypertensive ICH, 109–111 as modifiable risk factor for stroke, 45
and intravenous tissue plasminogen monitoring and treating, 46
activator (IV tPA), 4, 21–24 post IV tPA monitoring of, 4
142 INDEX
treating hypertensive ICH, 110, 111 secondary to arteriovenous malformation
treating patients with cerebral amyloid (AVM), 117–120
angiopathy, 115 incidence, 118
hypertensive intracerebral hemorrhage, treatment, 118–119, 120
109–111 secondary to cavernous malformation,
hypertonic saline, and reducing brain 121–123
edema, 32, 33, 38 symptomatic vs. asymptomatic, 23
hypothermia, and reducing brain edema, 33 intracranial aneurysm, asymptomatic,
135–138
infarct, images of complications and likelihood of rupture,
along right lateral ventricle, 90 136
bilateral chronic infarcts in a distal ICA treatment risk and benefit, 137
territory, 98 intracranial atherosclerosis, and secondary
left frontal, 66 stroke prevention, 61–63
patchy LMCA, 62 intradural vs. extradural aneurysm, 136
recent bilateral infarcts, 80 intraparenchymal hemorrhage, 84
right temporal and insular, 58 intravenous tissue plasminogen activator
internal carotid artery (ICA) (IV tPA)
asymptomatic stenosis, 49–52 hemorrhagic complications of, 4, 8, 9,
Moyamoya disease, 97–100 21–24
occlusion of both ICA, 99 hemorrhagic transformation after, 22
occlusion of left ICA, 74 hypertension monitoring and treatment,
persistent occlusion with robust collateral 4, 13–14
flow, 76 risk for intracerebral hemorrhage (ICH), 4
tapering occlusion of left ICA, 75 treating acute ischemic stroke, 1–5
international normalized ratio (INR), in benefits of, 2–3, 3–4
secondary stroke prevention, 65, 68 inclusion and exclusion criteria, 2–4,
International Study of Unruptured 3, 8, 13
Intracranial Aneurysms (ISUA), treating patients with minor symptoms,
136 28–29
International Subarachnoid Aneurysm Trial treating stroke mimic, 26
(ISAT), 137 use in patients with dissection, 75
International Surgical Trial in Intracerebral using lower dose of in “bridging therapy,” 16
Hemorrhage (STICH), 114 ISAT
intra-arterial prourokinase (proUK), 8 See International Subarachnoid
intra-arterial thrombolysis, and MCA Aneurysm Trial (ISAT)
occlusion, 8 ISUA
intracerebral hemorrhage (ICH) See International Study of Unruptured
hypertensive ICH, 109–111 Intracranial Aneurysms (ISUA)
and intravenous tissue plasminogen IV tPA
activator (IV tPA), 4, 21–24 See intravenous tissue plasminogen
predictors of after tPA, 23 activator (IV tPA)
INDEX 143
Labetolol, 13, 40 Mechanical Embolus Removal in Cerebral
lacunar stroke, 53–56 Ischemia (MERCI) Study, 8, 16
left-middle cerebral artery meningitis, and bacterial endocarditis,
(LMCA) 84
dense left MCA sign, 74 middle cerebral artery (MCA)
density in, 14, 15 hemicraniectomy for large MCA stroke,
infarct, 76 31–34
infarct and hemorrhagic transformation, infarct and hemorrhagic transformation,
22 22
infarct and stenosis, 62 infarction of complete RMCA territory,
signs of occlusion, 7, 8 32
stem occlusion, 16 left-middle cerebral artery (LMCA)
stenosis and transient ischemic attack, density in, 14, 15
106 signs of occlusion, 7, 8, 14
lenticulostriate vessels, 99 stem occlusion, 16
leviteracetam, 96 limited infarcts, 19
lisinopril, 40, 45 occlusion, 9
lobar hemorrhages, 114, 115 migraine headache
lumbar puncture and reversible cerebral vasoconstriction
diagnosing subarachnoid hemorrhage, syndrome, 103
127, 130 and signs of stroke, 25–26
and risk of dural venous sinus migrainous stroke, 89–91
thrombosis, 95 miosis, and Horner’s syndrome, 74
Moyamoya disease, 97–100
Management of Atherothrombosis with mycotic aneurysm due to bacterial
Clopidogrel in High Risk Patients endocarditis, 83–87
(MATCH) trial, 55
mannitol National Institute of Neurological Disorders
for cerebellar stroke, 35 and Stroke (NINDS)
and reducing brain edema, 32, 33 defining symptomatic hemorrhagic
Marfan’s syndrome, and spontaneous transformation, 23
dissection, 74 treating patients with minor symptoms,
mastoiditism, and risk of dural venous sinus 28
thrombosis, 95 trial of IV tPA, 2–3
MATCH trial nicardipine, 110
See Management of Atherothrombosis nimodipine, 128
with Clopidogrel in High Risk North American Symptomatic Carotid
Patients (MATCH) trial Endarterectomy Trial (NASCET),
mechanical clot retrieval 58
following IV tPA, 16
and MCA occlusion, 8–9 oral contraceptive use, and risk of dural
recanalization following, 17 venous sinus thrombosis, 95
144 INDEX
otitis, and risk of dural venous sinus proton pump inhibitors (PPIs), and
thrombosis, 95 interaction with clopidogrel, 54
proUK
paradoxical embolus, and cryptogenic See intra-arterial prourokinase (proUK)
stroke, 70 ptosis, and Horner’s syndrome, 74
parasagittal intraparenchymal hemorrhage, 84 puerperium
patent foramen ovale (PFO) and reversible cerebral vasoconstriction
and cryptogenic stroke, 69, 70, 71 syndrome, 103
and stroke in young adults, 80 and risk of dural venous sinus
Patient Foramen Ovale in Cryptogenic thrombosis, 95
Stroke Study (PICSS), 70 punctate infarcts in left frontal cortex, 28, 29
Penumbra device for clot retrieval, 8–9
perfusion pressure, 40 radiosurgery
perimesencephalic subarachnoid for cavernous malformation, 123
hemorrhage, 131–133 treating arteriovenous malformation
prognosis vs. non-perimesencephalic, (AVM), 118, 120
132 recanalization
subarachnoid hemorrhage in suprasellar after mechanical thrombectomy, 17
cistern, 132 “bridging therapy,” 16
PICSS and carotid artery dissection, 75
See Patient Foramen Ovale in and intravenous tissue plasminogen
Cryptogenic Stroke Study (PICSS) activator (IV tPA), 15, 15–16
pregnancy and mechanical clot retrieval, 8–9
and reversible cerebral vasoconstriction of occluded MCA branch artery, 10
syndrome, 103 occlusion and, 18
and risk of dural venous sinus reperfusion therapy for acute ischemic
thrombosis, 95 stroke, 13–20
preventing stroke, 43–47 revascularization
evaluation for risk factors, 45 and carotid stenosis, 50–51,
silent infarcts, risk factors and incidence, 58, 59
44 to treat Moyamoya disease, 98–100
Prevention Regimen for Effectively reversible cerebral vasoconstriction
Avoiding Second Strokes syndrome, 101–104
(PROFESS) trial, 54 right lateral ventricle, compression of, 32
primary prevention of stroke, 43–47 right middle cerebral artery (RMCA)
evaluation for risk factors, 45 hemicraniectomy for large MCA stroke,
silent infarcts, risk factors and incidence, 31–34
44 infarction of complete RMCA territory,
Prolyse in Acute Cerebral 32
Thromboembolism Trial risk-assessment scales for stroke
(PROACT), 8 ABCD2 for transient ischemic attack
prothrombin complex concentrate, 110 (TIA), 106, 106
INDEX 145
risk-assessment scales for stroke (cont.) SPS3 trial
CHADS2, 66, 68 See Secondary Prevention of Small
Framingham Stroke Profile, 46 Subcortical Strokes (SPS3) trial
Spetzler-Martin Scale and arteriovenous statins
malformation, 118, 119 for intracranial atherosclerosis, 63
risk factors, evaluation for, 44–45, 80, 82 secondary stroke prevention
rivaroxaban, 68 after cryptogenic stroke, 71
ruptured vs. unruptured aneurysm, 136 after lacunar stroke, 54, 55
for transient ischemic attack (TIA), 106
SAMMPRIS trial stenosis
See Stenting and Aggressive Medical asymptomatic of internal carotid artery
Management for Preventing (ICA), 49–52
Recurrent Stroke in Intracranial angiography of, 51
Stenosis (SAMMPRIS) trial angioplasty, 50–51
Secondary Prevention of Small Subcortical carotid endarterectomy, 50
Strokes (SPS3) trial, 55 medical management of, 50, 51, 52
secondary stroke prevention and carotid artery dissection, 75
after cardioembolic stroke, 65–68 carotid stenosis and secondary stroke
after cryptogenic stroke, 69–71 prevention, 57–59
after lacunar stroke, 53–56 focal stenoses, 103
after stroke due to carotid stenosis, left MCA, 62
57–59 and risk of recurrent stroke, 62
after stroke due to intracranial Stenting and Aggressive Medical
atherosclerosis, 61–63 Management for Preventing
after subarachnoid hemorrhage, 128 Recurrent Stroke in Intracranial
after transient ischemic attack (TIA), Stenosis (SAMMPRIS) trial, 63
106, 107 stenting and angioplasty
selective serotonin reuptake inhibitors angiography, 51
(SSRIs), 103 in ICA stenosis, 50–51
sickle cell disease, and Moyamoya disease, 98 perioperative stroke, 59
silent infarcts, risk factors and incidence, 44 secondary stroke prevention
simvastatin, 53 after stroke due to carotid stenosis, 58
smoking cessation, and stroke prevention, 63 after stroke due to intracranial
sociodemographic factors in treating atherosclerosis, 63
hypertension, 45 STICH trial
Solitaire With the Intention For See International Surgical Trial in
Thrombectomy Trial (SWIFT), 8–9 Intracerebral Hemorrhage (STICH)
SPARCL trial stroke
See Stroke Prevention by Aggressive incidence in United States, vii
Reduction of Cholesterol Levels managing hypertension, 39–41
(SPARCL) trial migrainous stroke, 89–91
Spetzler-Martin Scale, 118, 119 primary prevention, 43–47
146 INDEX
rapid improvement as ominous sign, 28 suboccipital craniectomy, 38
risk-assessment scales, 46 suboccipital decompression
risk factors for, 45 for cerebellar stroke, 35–38
secondary stroke prevention treating intracerebral hemorrhage,
after cardioembolic stroke, 65–68 119
after cryptogenic stroke, 69–71 SWIFT
after lacunar stroke, 53–56 See Solitaire With the Intention for
after stroke due to carotid stenosis, Thrombectomy Trial (SWIFT)
57–59 Sylvian fissure, hyperdensity in, 14, 15
after stroke due to intracranial sympathomimetic drugs, 103
atherosclerosis, 61–63
after subarachnoid hemorrhage, 128 thrombectomy
silent infarcts, risk factors and incidence, following IV tPA, 16
44 and MCA occlusion, 8–9
stroke in a young adult, 79–82 recanalization following, 17
stroke mimic thrombophilia, hereditary, 95
migraine headache, 25–26, 90 thrombosis, dural venous sinus,
treatment with IV tPA, 26 93–96
treating minor symptoms, 27–29 thrombotic thrombocytopenic purpura
Stroke Prevention by Aggressive Reduction (TTP), 81
of Cholesterol Levels (SPARCL) “thunderclap headache,” 101, 102, 132
trial, 54 transient ischemic attack (TIA),
subarachnoid hemorrhage (SAH) 105–107
hyperintensities in sulci consistent with
SAH, 102 vasoconstriction syndrome, reversible
small SAH, 84 cerebral, 101–104
subarachnoid hemorrhage, aneurysmal, vasospasm, 128
125–130 venous anomaly, developmental,
hospitalization and treatment, 128 123
Hunt Hess grading system for ventriculostomy drain, 38
neurological deficit, 127, 128 verapamil, 103
images, 126, 127 vitamin K, intravenous, 110
morbidity and mortality rates, 126, vomiting, and dissection of cervical carotid
130 artery, 74
subarachnoid hemorrhage,
perimesencephalic, 131–133 warfarin
prognosis vs. non-perimesencephalic, and patients with hypertensive ICH,
132 110, 111
subarachnoid hemorrhage in secondary stroke prevention
suprasellar cistern, 132 after cardioembolic stroke, 65, 68
and “thunderclap” headaches, 102, 104 after cryptogenic stroke, 70
subcutaneous heparin, 111 after stroke from dissection, 75, 77
INDEX 147
warfarin (cont.) weight loss, and stroke prevention, 63
in intracranial atherosclerosis, 62–63 white matter hyperintensities, 44
treating dural venous sinus thrombosis,
96 young adults
withholding therapy, 85, 86 migraine headache and risk of stroke,
Warfarin-Aspirin Symptomatic Intracranial 90
Disease Trial (WASID), 62 as stroke patients, 79–82
148 INDEX