The n e w e ng l a n d j o u r na l
case records of the massachusetts general hospital
From the Cardio-Neurology Clinic, Depart-
ment of Neurology (M.M.N.), and the
Department of Radiology (R.G.G.), Mas-
sachusetts General Hospital; and the De-
partments of Neurology (M.M.N.) and Ra-
diology (R.G.G.), Harvard Medical School
both in Boston.
N Engl J Med 2013;369:1736-48.
DOI: 10.1056/NEJMcpc1302431
Copyright 2013 Massachusetts Medical Society.
1736
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of m e dic i n e
Founded by Richard C. Cabot
Eric S. Rosenberg, m.d., Editor Nancy Lee Harris, m.d., Editor
Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor
Sally H. Ebeling, Assistant Editor Emily K. McDonald, Assistant Editor
Case 34-2013: A 69-Year-Old Man
with Dizziness and Vomiting
MingMing Ning, M.D., and R. Gilberto Gonzalez, M.D., Ph.D.
Pr e sen tat ion of C a se
Dr. Minjee Kim (Neurology): A 69-year-old man was admitted to this hospital because
of dizziness and vomiting.
The patient had been well until 4:15 a.m. on the day of admission, when he
became dizzy, diaphoretic, and weak and had sensations of rocking and counter-
clockwise movement after he rolled onto his stomach in bed. The symptoms
improved when he rolled into the supine position, and he slept until 7 a.m.; on
awakening, the symptoms recurred. When walking, he sensed he was tilting to the
left but did not fall. The symptoms worsened throughout the morning; they were
most severe with head movements and were associated with increasing nausea
and, after 10 a.m., vomiting. He called his doctors office because of concern that
he was having a stroke. He was advised to go the hospital and called emergency
medical services. On examination, his skin was pale and dry and the blood pres-
sure was 148/60 mm Hg; the other vital signs and the remainder of the examina-
tion were normal. He was brought to the emergency department at this hospital,
arriving approximately 9 hours after the onset of symptoms.
The patient reported facial tingling in the area surrounding the eyes, including
the malar eminence, and a mild headache. He noted that his visual perception
momentarily lagged behind his eye movements, and the lag was more severe when
looking to the right than to the left. He had no diplopia, blurred vision, tinnitus,
decreased hearing, difficulty swallowing, changes in sensation or strength, palpita-
tions, chest pain, fever, or shortness of breath. He reported an episode of self-limited
positional vertigo that had occurred several years earlier. He had hypertension,
hyperlipidemia, asthma, sleep apnea (for which he intermittently used continuous
positive airway pressure at night), depression, meralgia paresthetica (apainful
mononeuropathy of the lateral femoral cutaneous nerve), erectile dysfunction, and
recurrent localized herpes simplex virus infection. He was left-handed. His daily
medications included rosuvastatin, valsartan, hydrochlorothiazide, duloxetine,
aspirin, and a multivitamin. He also received, as needed, a topical lidocaine patch
for meralgia paresthetica; gabapentin for pain; vardenafil (though he had not
taken it recently); fluticasone propionate nasal spray and inhaler, albuterol, and
n engl j med 369;18nejm.orgoctober 31, 2013
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 case records of the massachuset ts gener al hospital
loratadine for wheezing and asthma; and vala-
cyclovir. He swam regularly, drank wine daily,
and did not smoke. His siblings had arthritis
and hypercholesterolemia, and his children and
grandchildren were healthy.
On examination, the patient was alert and
oriented. The skin was pale and diaphoretic. The
blood pressure was 123/89 mm Hg, and the pulse
58 beats per minute; the other vital signs and
oxygen saturation were normal. The sensation of
light touch was slightly decreased over the malar
eminence and the jaw on the left side and was
normal over the eyelids, frontalis muscle, and
upper neck. There was nystagmus on left lateral
gaze, and sustaining left lateral gaze required
some effort; the eye movements were slower
from midline to the left than from midline to
the right. He was able to reproduce the sensation
of delayed visual return, which was more severe
when moving his head to the right than to the
left. When he was not supported, he tilted to the
left. He walked cautiously and slowly, with a
slightly broad-based gait, and was unable to
perform tandem walking. Deep-tendon reflexes
were slightly more brisk on the right side than
on the left side. The remainder of the neuro-
logic and general examinations was normal.
The blood level of carbon dioxide was
21.9mmol per liter (reference range, 23.0 to 31.9),
the level of glucose was 164 mg per deciliter
(9.1mmol per liter; reference range, 70 to 110 mg
per deciliter [3.9 to 6.1 mmol per liter]), the level
of phosphorus was 1.2 mg per deciliter (0.4 mmol
per liter; reference range, 2.6 to 4.5 mg per deci-
liter [0.8 to 1.5 mmol per liter]), and the anion gap
was 16 mmol per liter (reference range, 3 to 15).
Blood levels of other electrolytes, calcium, and
magnesium were normal, as were results of the
complete blood count and tests of coagulation,
renal function, and liver function; screening for
troponin I was negative. An electrocardiogram
(ECG) showed sinus rhythm at a rate of 59 beats
per minute and no acute ischemic changes. Lo-
razepam, ondansetron, and intravenous fluids
were administered, and the patients condition
partially improved.
Dr. R. Gilberto Gonzalez: Approximately 2 hours
after the patients arrival, computed tomography
(CT) of the brain, performed without the admin-
istration of contrast material, revealed normal
brain parenchyma and an extraaxial calcified
lesion, 9 mm by 16 mm by 6 mm, in the left
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parafalcine area over the high parietal convexity;
there was no intracranial hemorrhage, extraaxial
collection, mass effect, or midline shift.
Dr. Kim: The patient was admitted to the ob-
servation unit at this hospital.
A diagnostic procedure was performed.
Differ en t i a l Di agnosis
Dr. Eric S. Rosenberg (Pathology): Dr. MingMing
Ning, our discussant today, is not aware of the
diagnosis in this case. We also have with us the
patient under discussion, who has agreed to an-
swer any questions that Dr. Ning may have about
his initial presentation.
Dr. MingMing Ning: When this event started, ac-
cording to the history, you had rolled over in bed.
Can you describe to me exactly what happened?
The Patient: I woke up lying on my stomach,
and the room was spinning. I was sweating so
profusely that I had to wring out my T-shirt and
take it off.
Dr. Ning: Did you sit up?
The Patient: I sat up briefly. I went back to sleep
on my back for a few hours and then woke up. The
spinning was less severe, but it was still there.
Dr. Ning: What thoughts went through your
mind when you went back to sleep? This must
have been pretty disturbing. Why didnt you call
for help?
The Patient: I dont know why I didnt call
forhelp.
Dr. Ning: I understand that you do a lot of
vigorous exercise, including swimming. Had you
done anything unusual before this episode?
The Patient: I generally swim 5 days a week. I do
a freestyle stroke for 1 or 2 miles, or I occasion-
ally do a modified butterfly stroke or a breast-
stroke. The day before the episode, I swam three
fourths of a mile, mostly doing a freestyle stroke,
as part of my training for a triathlon.
Dr. Ning: I will focus on the thought process
(including the identification of clinical pearls and
red flags) and the appropriate workup involved
in evaluating a patient with a neurologic event.
Summary of the Present Illness
First, I will try to identify the anatomical local-
ization and cause of the present illness from the
history provided.
The patient is a 69-year-old, left-handed avid
swimmer who, after rolling onto his stomach in
1737
 The n e w e ng l a n d j o u r na l
bed, noted vertigo, diaphoresis, and the develop-
ment of progressive and fixed symptoms, includ-
ing tilting to the left, nausea, vomiting, headache,
oscillopsia (the visual perception of objects moving
when they are actually stationary), and changes in
facial sensation. Neurologic symptoms can be
localized to the central nervous system or the
peripheral nervous system; most of the signs
and symptoms in this case are of central origin.
The central nervous system is roughly divided
into the supratentorial and infratentorial regions.
Abnormalities in the two regions have some
common manifestations, such as unilateral weak-
ness and loss of sensation. Patients with supra-
tentorial lesions (i.e., lesions in the frontal, pari-
etal, temporal, or occipital lobe) can present with
cortical signs, such as aphasia, neglect, difficulty
with higher cognitive functions (e.g., calculation
or praxis), confusion, and visual-field deficits.
Patients with infratentorial lesions (i.e., lesions in
the brain stem or cerebellum) can present with
cranial-nerve abnormalities and cerebellar signs,
such as dysarthria, double vision, difficulty swal-
lowing, nystagmus, oscillopsia, dysmetria, ataxia,
gait imbalance, nausea, and vertigo.
In this case, the constellation of symptoms
and the lack of cortical signs indicate that the le-
sion is localized to the brain stem and cerebellum.
Occasionally, patients with a mass or demyelinat-
ing lesion adjacent to the cerebral ventricles or
aqueduct can have rapid-onset hydrocephalus,
which is associated with symptoms similar to
those seen in this case. However, the sudden on-
set of illness and the rapid progression within a
few hours, in the absence of other subacute signs,
are suggestive of a focal neurovascular event.
There are several crucial signs in this case.
The first important sign is that the patient rolled
over onto the abdomen in bed that is, he
performed a passive Valsalva maneuver. The Val-
salva maneuver is associated with active cough-
ing, heavy lifting, constipation, or passive pres-
sure on the abdomen that alters atrial pressure.
The maneuver can cause paradoxical embolic
stroke by forcefully opening a patent foramen
ovale and allowing venous clots to travel to the
brain.1 Change in body position can also move
otoliths in the semicircular canals of the inner
ear2 or stretch vertebral blood vessels traveling
inside the cervical spinous processes.
Cardiac ischemia triggers hyperactivity of the
autonomic nervous system and is commonly as-
sociated with diaphoresis, but it is rarely associ-
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of m e dic i n e
ated with true vertigo, a normal ECG, or negative
screening results for troponin I. On rare occa-
sions, during vertebrobasilar stenosis or clot-
ting, low flow due to cardiac failure can trigger
brain-stem ischemia, which is manifested as cen-
tral vertigo. In addition, the brain can activate au-
tonomic instability,3 and posterior-circulation in-
farcts can be associated with hyperhidrosis.4-6 The
spinning sensation, or true vertigo, is of central
origin (Table 1).2,7 Peripheral vertigo (a dysfunc-
tion of the peripheral vestibular system) is more
prevalent than central vertigo in the general popu-
lation, but peripheral vertigo should be a diagno-
sis of exclusion in patients with vascular risk fac-
tors. Central vertigo is associated with lesions in
the posterior fossa (i.e., the brain stem and cere-
bellum), and its symptoms including nausea,
vomiting (due to increased intracranial pressure),
inability to walk (due to ataxia or weakness), and
headache can often be mistakenly attributed to
gastroenteritis. Vertebrobasilar stroke should be
considered because its consequences are devastat-
ing; it is associated with up to 50% mortality.8
Medical History
Assessment of the patients medical history is cru-
cial for putting his acute symptoms in the context
of other risk factors. It is important to identify tra-
ditional risk factors (e.g., hypertension and hyper-
lipidemia, both present in this patient), as well as
emerging risk factors (e.g., sleep apnea, migraine
with aura, and genetic variants such as CADASIL
[cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy]).
This patient had meralgia paresthetica and erectile
dysfunction, which may point to underlying diabe-
tes or uncontrolled hypertension; we often discover
glucose intolerance or diabetes during a diagnostic
workup for stroke. Chronic inflammatory condi-
tions (e.g., recurrent localized herpes simplex
virus infection and arthritis) may contribute to
clotting and vascular risk factors. Furthermore,
the patient, as an avid swimmer and triathlete, is
at risk for neck injury. In view of the risk factors,
a vascular cause of his symptoms (i.e., acute stroke)
is likely.
Clinical Examination
Clinical examination can help to distinguish
central vertigo from peripheral vertigo (Table 1).
The presence of asymmetric deep-tendon reflex-
es indicates a central phenomenon, but diabetic
neuropathy can obliterate these reflexes. In cen-
 case records of the massachuset ts gener al hospital

Table 1. Signs and Symptoms Associated with Central and Peripheral Vertigo.

Sign or Symptom
Nystagmus
Response to provocative ma-
neuvers (e.g., as deter-
mined by Brnys test or
DixHallpike test)
Nausea, vomiting, or both
Ataxia and gait imbalance
Cranial-nerve findings (e.g.,
those pertaining to hear-
ing, swallowing, facial
sensation, tongue
strength)
Posture dependency
Manifestation in
Central Vertigo
Horizontal, vertical, or rotatory Horizontal or rotatory; can be In central vertigo, downbeat is associated
(toward side of lesion)
Short or no latency
Variable; associated with
increased intracranial
pressure
Wide-based, ataxic gait
Present
Sometimes
Manifestation in
Peripheral Vertigo Comments
variable (usually away from with craniocervical junction or cere
lesion) bellum (e.g., in Chiari malformation)
and upbeat is associated with medul-
lary lesions (e.g., in multiple sclerosis).
Latency 25 sec To measure response, quickly (in <2 sec)
bring patient from sitting position to
supine position with head turned to
one side and eyes open, and observe
nystagmus and vertigo for >1 min.
Variable Nausea and vomiting can occur in pa-
tients who have either central or pe-
ripheral vertigo, can be more severe in
peripheral vertigo at onset, and can of-
ten be accompanied by headache in
central vertigo.
Narrow-based, unsteady gait Central vertigo (i.e., due to cerebellar le-
sions) causes leaning to one side or
the inability to stand or walk.
Absent The presence of cranial-nerve findings
helps to determine the level of injury
in the posterior fossa.
Usually Peripheral vertigo tends to be more po
sition dependent than does central
vertigo.

tral horizontal nystagmus, the fast phase is to- Hemorrhagic Stroke

ward the side of the lesion, indicating involve-
ment of the left cerebellum in this case. The loss
of facial sensation in this patient may be related
to focal injury in the medulla near the fifth cra-
nial nerve. The examination is localized to a par-
tial territory of the posteroinferior cerebellar
artery (Fig. 1); a full-blown infarct of a postero
inferior cerebellar artery (Fig. 1B and 1C), or the
lateral medullary syndrome, is relatively rare, since
the vascular pathological features have various
thromboembolic distributions.9,10
Differential Diagnosis of Stroke
In the United States, stroke is the leading cause of
serious long-term disability; one person dies from
stroke every 4 minutes, and one in four patients
with stroke have recurrent strokes. The two major
types of stroke are ischemic (caused by a lack of
blood flow and accounting for 87% of strokes)
and hemorrhagic (caused by a blood-vessel rup-
ture and accounting for 13% of strokes).11 Symp-
toms of the two types differ but can overlap as
a result of anatomical variance, handedness, or
other genetic factors.11
Hemorrhagic strokes are roughly classified ac-
cording to location; the subtypes are subarach-
noid, epidural, subdural, and intraparenchymal.
In this patient, the lack of early severe headache
and lack of progression to global alterations in
consciousness make subarachnoid hemorrhage
an unlikely diagnosis. Epidural hemorrhage, com-
monly due to traumatic injury of the middle men-
ingeal artery, occurs in persons who are in a
younger age group (i.e., <45 years of age) and
whose skull and dura are more easily separated. In
persons in this patients age group (i.e., >65 years
of age), subdural hemorrhage can cause progres-
sive focal neurologic changes, especially after
trauma, and an acute-on-chronic subdural hemor-
rhage can cause seizures in those who are taking
anticoagulant drugs. Recently recognized causes
of intraparenchymal hemorrhage, such as cerebral
amyloid angiopathy, may result in an indolent dis-
ease course and cognitive changes.12 Intraparen-
chymal hemorrhage due to hypertension is a pos-
sible diagnosis in this case; it commonly occurs in
the cerebellum and basal ganglia.
It is very important to distinguish ischemic

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Posterior cerebral artery

B Superior cerebellar artery

A
Basilar artery

Anteroinferior
cerebellar artery

Vertebral
artery

Posteroinferior
cerebellar artery
Posteroinferior
cerebellar artery

IV
Vertebral artery Sympathetic tract
(intradural portion) Fifth-cranial-
C nerve tract
Vertebral artery
III (extradural portion)

Internal carotid artery

II External carotid Tenth-cranial-

artery nerve tract

Vertebral artery Spinothalamic tract

I Common carotid artery
Subclavian artery
D C1

C2

Vertebral artery C3
Vertebral artery
C4

C5

Figure 1. Anatomy and Mechanism of Vascular Injury in Vertebral-Artery Dissection.

Panel A shows the four segments of the vertebral artery. In segment I, the vertebral artery begins at the subclavian artery and spans to
the transverse foramen of C5 or C6; in segment II, the vertebral artery is enclosed within the transverse foramina and spans from C5 or
C6 to C2; in segment III, the vertebral artery continues from the transverse foramen of C2 and passes between the atlas and the occiput
(the most common dissection site); and in segment IV (i.e., the intradural portion), the vertebral artery enters the dura COLOR at the foramen
FIGURE

magnum and merges with the contralateral vertebral artery to form the proximal basilar artery. Panel B shows Rev4the cerebellum; the blood
09/30/13
supply to the cerebellum and part of the medulla comes from the posteroinferior cerebellar artery. Patients who have strokes associated
Author Dr. Ning
with the posteroinferior cerebellar artery have cerebellar and medullary-cranial-nerve symptoms (e.g., vertigo, nystagmus, ipsilateral
limb ataxia, and dysarthria). Panel C shows a cross section of the medulla in the territory of the postero Fig #
inferior 1
cerebellar artery and the
Title
structures affected by stroke; these include the fifth-cranial-nerve tract (which causes ipsilateral loss of facial sensation), the spinotha-
lamic tract (which causes contralateral loss of limb and trunk sensation), the tenth-cranial-nerve tract ME(which causes ipsilateral pharyn-
geal and laryngeal paralysis), and the sympathetic tract (which causes ipsilateral Horner syndrome). Panel DE D shows bow-hunters syn-
drome, which occurs when rotation of the neck to the right causes tethering, compression, and mechanical Artist tearingDaniel
of the Muller
left vertebral
artery in segment III. AUTHOR PLEASE NOTE:
Figure has been redrawn and type has been reset
Please check carefully

Issue date 10/31/2013

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 case records of the massachuset ts gener al hospital

stroke from hemorrhagic stroke, because the treat-

Table 2. Prevalence of Stroke Mechanisms According to Age Group.*
ments are completely different. Dr. Gonzalez has
reviewed the crucial cranial CT scan, which rules Prevalence in Prevalence in
out the diagnosis of clinically significant hemor- Younger Age Older Age
Group Group
rhage. The incidental intraaxial lesion cannot Stroke Mechanism (1844 yr) (>65 yr)
explain the symptoms; such a lesion could cause
seizures but not fixed deficits. percent
Cardiac embolism 31 29
Ischemic Stroke Large-vessel atherosclerotic disease 3 16
Venous strokes due to cerebral venous thromboses Small-vessel disease 20 16
are less common than arterial ischemic strokes; Hematologic disease 20
they develop over days or weeks and frequently go
Nonatherosclerotic vasculopathy 11
undetected. Venous hypercoagulability, worsening
Illicit-drug use 9
headache, changes in visual acuity, papilledema,
or the late development of a hemorrhagic lesion Oral-contraceptive use 5
(due to venous congestion) should prompt an ur- Migraine 1
gent workup for cerebral venous thrombosis. Ar- Other 3
terial strokes, which account for the majority of Unknown 36
ischemic infarcts, comprise thrombotic (large-
vessel or small-vessel) strokes, embolic (cardio- * Data are from Kittner et al.13 and Petty et al.14
embolic or paradoxical embolic) strokes, and other
vasospastic variants (Table 2).13,14 A large propor-
tion (>30%) of arterial strokes are cardioembolic, thrombotic stroke because emboli seldom affect
regardless of the age group of the patients. Age, the same territory repeatedly.
cognitive status, sex, and race were traditionally
used to identify stroke subtype; older age is asso- Individualized Workup for Stroke
ciated with large-vessel atherosclerotic disease, The patient will need to undergo an individualized
cognitive impairment with small-vessel disease, diagnostic workup (Table 3). He will undergo mag-
and younger age with traumatic dissection and netic resonance imaging (MRI) of the brain and its
congenital abnormalities.14-18 As the population vasculature, as well as cardiac evaluation, because
lives longer, age may not be reliable in the iden- of the high prevalence of embolic stroke.19 We have
tification of stroke subtypes, and an individual formed a cardioneurology clinic at this hospital to
patient may have multiple causes of stroke. New evaluate the health of the heart in terms of stroke
causes of strokes in the cryptogenic category risk and treatment, since up to 50% of ischemic
(i.e., strokes of unclear cause after a standard strokes involve the heart and since large-vessel ar-
workup) have been discovered, including genetic terial disease and cardioembolic disease can coex-
variants (e.g., CADASIL), subclinical paroxysmal ist, in part because they have shared cardiovascular
atrial fibrillation undetected by short-term cardiac risk factors.1 The brain is the upstairs neighbor
monitoring, and cardiac abnormalities (e.g., patent of the heart and on the receiving end of ischemic
foramen ovale).18-20 Patent foramen ovale is associ- injury, and thus monitoring circulatory brainheart
ated with more than 40% of cryptogenic strokes.1 communication is crucial for stroke prevention.
This patient crosses these traditional stroke For example, the right-to-left shunting through a
categories. He is at risk for atherothrombotic patent foramen ovale not only allows clots to go
disease because of his age and the presence of through but also increases oxidative stress in the
hyperlipidemia and hypertension. However, he blood, elevating the risk of future events.20 Blood
appears younger than his stated age and is a lipid levels and inflammatory and individualized
swimmer, and thus he is also at risk for stroke clotting profiles should be obtained to stratify
subtypes associated with younger age, such as stroke risk for future management (Table 3).
traumatic dissection and paradoxical embolism
due to a patent foramen ovale. If his previous Summary
episode of vertigo was associated with a tran- In summary, in view of the sudden-onset, pro-
sient ischemic attack, then a likely diagnosis is gressive, fixed neurologic deficits, the history of

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 The n e w e ng l a n d j o u r na l of m e dic i n e

potential neck injury, and the risk factors for
thromboembolic disease, my leading diagnosis
is ischemic stroke due to vertebral-artery dissec-
tion, resulting in artery-to-artery emboli in the
territory of the posteroinferior cerebellar artery.
A cardioembolic event is also in the differential
diagnosis. Because the risk factors for and the
causes of various stroke subtypes can overlap,
the next step is a comprehensive workup for
stroke that includes vascular imaging, as well as
cardiac and hematologic testing tailored to the
patients risk factors.
Dr. Rosenberg: Dr. Kim, would you tell us the
thinking of your team during evaluation of the
patient?
Dr. Kim: We were concerned that a vascular
event, either hemorrhagic or ischemic stroke, had
occurred between the time the patient went to bed
and the time he first woke up, at 4:15 a.m. We be-
lieved that the event was most likely localized to the

Table 3. Testing to Perform during an Individualized Workup for Stroke.

Test Indication
Imaging
CT (noncontrast) To distinguish hemorrhagic infarct from ischemic infarct; perform urgently to tri-
age for intravenous tissue plasminogen activator
CT angiography To detect arterial vascular abnormalities (e.g., cerebral aneurysm; if detection is
likely, use conventional cerebral angiography), carotid disease, intracranial
stenosis, aortic atheroma, or dissection
CT venography To detect venous vascular abnormalities (e.g., cerebral venous thrombosis)
MRI Use apparent-diffusion-coefficient sequence of diffusion-weighted imaging to detect
an acute ischemic infarct; T2-weighted or fluid-attenuated inversion recovery
sequence to detect chronic emboli or small-vessel disease; T1-weighted sequence,
with and without contrast enhancement, to detect a space-occupying lesion; and
susceptibility-weighted imaging to detect microhemorrhage related to remote
hypertensive bleeding or cerebral amyloid angiopathy
Magnetic resonance angiography Use fat-saturation sequence to detect dissection, carotid disease, or intracranial
stenosis
Magnetic resonance venography To detect venous vascular abnormalities (e.g., cerebral venous thrombosis)
Carotid ultrasonography To assess flow and degree of stenosis
Transcranial Doppler ultrasonography To monitor intracranial stenosis, assess progression of carotid stenosis (e.g.,
reversal of ophthalmic-artery flow), or detect vasospasm associated with
subarachnoid hemorrhage; perform with the injection of agitated saline to
screen for patent foramen ovale
Dynamic transcranial or extracranial Doppler ultrasonog- To assess blood flow with respect to head and neck movement or to detect cere-
raphy bral embolus
Hematologic
Conventional risk stratification
Lipid panel and thyroid screening To determine the risk of atherosclerosis and cardiac arrhythmia
Glycated hemoglobin (goal, <6.5%) or fasting glucose To determine the risk of diabetes
Cardiac enzyme Chest pain or abnormal electrocardiogram
Vitamin B12, folate, and homocysteine To determine nutritional status (i.e., risk of gastric bypass or malnutrition,
presence of ethanol)
Erythrocyte sedimentation rate, C-reactive protein, or To detect endocarditis
blood culture
Toxicologic screening of blood and urine To identify use of cocaine, marijuana, or other vasospastic or illicit drugs
d-dimer, partial-thromboplastin time, and activated To determine coagulation status (antifactor Xa, thrombin time, and ecarin
partial-thromboplastin time clotting time may be measured in patients taking factor Xa inhibitors or
thrombin inhibitors)
Protein C, protein S, lupus anticoagulant, antiphospho- Ischemic stroke; use to determine venous hypercoagulability in order to identify
lipid antibodies, prothrombin gene mutation, and pregnancy, use of oral contraceptives, smoking status, and risk of paradoxical
antithrombin III embolism

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 case records of the massachuset ts gener al hospital
Table 3. (Continued.)
Test
Homocysteine and lipoprotein(a)
Fibrillin-1 (FBN1), collagen type I (COLIA1), collagen
type II (COLIA2), and GLA
Partial-thromboplastin time, activated partial-thrombo-
plastin time, and von Willebrand factor
Cardiac
Electrocardiography
Holter monitoring or extended cardiac monitoring
Transthoracic echocardiography
Transesophageal echocardiography
Other
Pulmonary sleep studies
Peripheral vascular
Renal-artery stenosis
Doppler ultrasonography of the legs
Pelvic magnetic resonance venography or CT venog-
raphy
Subclavian CT angiography or magnetic resonance
angiography
cerebellum. We were concerned that he had a trau-
matic dissection that caused a posterior-circulation
infarct. Nine or 10 hours had already passed since
symptom onset, so the window of time during
which he could undergo thrombolysis with intra-
venous tissue plasminogen activator (t-PA) had
closed. CT without the administration of contrast
material was performed to rule out the presence
of hemorrhage. The patient then underwent MRI
and magnetic resonance angiography (MRA).
Cl inic a l Di agnosis
Cerebellar ischemic stroke, possibly due to verte-
bral-artery dissection.
DR . MingMing NINGs DI AGNOSIS
Cerebellar ischemic stroke due to vertebral
artery dissection, with artery-to-artery emboli in
a partial territory of the posteroinferior cerebellar
artery.
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Indication
Ischemic stroke; use to determine arterial hypercoagulability as risk factor for
diffuse intracranial or extracranial stenosis
Ischemic stroke; use to detect spontaneous dissection with high suspicion for
collagen vascular disease (i.e., Marfans syndrome, osteogenesis imperfecta,
EhlersDanlos syndrome) or Fabrys disease (deficiency in -galactosidase A)
General workup for hemorrhagic stroke; perform tests for other clotting factors if
abnormality is detected
To detect myocardial infarction and arrhythmia
To detect cardiac arrhythmia, especially atrial fibrillation
To assess ejection fraction (<30%) and left atrial size (as a risk factor for atrial
fibrillation; >40 mm anteroposterior) and to screen for patent foramen ovales
(as risk factor for paradoxical embolism; features include atrial septal aneu-
rysm, significant right-to-left shunting); perform with the injection of agitated
saline
Likelihood of endocarditis (or other valvular lesions) or atrial thrombus
To detect obstructive sleep apnea
Younger patients with hypertensive hemorrhage
To detect deep-vein thrombosis as risk factor for paradoxical embolism
To detect MayThurner features as risk factor for peripheral venous compression
To detect subclavian steal syndrome, which causes transient ischemic attack
Discussion of Im aging
Dr. Rosenberg: Dr. Gonzalez, would you make the
diagnosis for us?
Dr. Gonzalez: MRI and MRA were performed.
The diffusion-weighted images show a single
hyperintense abnormality involving the medial
left cerebellum and vermis (Fig. 2A); the ab
normality is hypointense on the apparent-
diffusion-coefficient images, a finding that
confirms that this is an acute infarction. On
T2-weighted images (not shown) and fluid-at-
tenuated inversion recovery images (Fig. 2B), a
hyperintense abnormality is identified at pre-
cisely the same location as on the diffusion-
weighted images, findings that suggest that the
acute infarction occurred more than 6 hours
earlier. MRA revealed normal, widely patent,
bilateral carotid and right vertebral arteries
(Fig. 2C); however, the left vertebral artery is
poorly visualized (Fig. 2D). Images from MRI
scans suggest acute left cerebellar infarction
1743
 The n e w e ng l a n d j o u r na l of m e dic i n e

A B

C D

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 case records of the massachuset ts gener al hospital
Figure 2 (facing page). MRI and Magnetic Resonance
Angiography of the Brain.
A diffusion-weighted image of the cerebellum shows a
hyperintense focus (Panel A, arrow), which is sugges-
tive of acute ischemic infarction. A fluid-attenuated in-
version recovery MRI scan of the cerebellum shows a
hyperintense focus (Panel B, arrow), which is consis-
tent with the finding on the diffusion-weighted image
and suggests that the infarction occurred more than 6
hours earlier. A magnetic resonance angiogram (MRA)
of the right vertebral and carotid arteries shows normal
flow-related enhancement of all the arteries on the right
side, including the right vertebral arteries (Panel C, ar-
rows). An MRA of the left vertebral and carotid arteries
shows that the left vertebral artery is poorly, intermit-
tently visualized (Panel D, arrows), a finding that is
suggestive of an arterial dissection.
due to a dissection of the left vertebral artery.
CTangiography was performed to confirm the
diagnosis of dissection; the images show a
normal right vertebral artery, but the left verte-
bral artery is enhanced intermittently, confirm-
ing that the presence of a dissection is likely.
Discussion of M a nagemen t
Dr. Rosenberg: Dr. Ning, would you tell us how you
would manage this case?
Dr. Ning: Appropriate management and second-
ary prevention of acute ischemic stroke must
target the underlying cause.
Management of acute Ischemic Stroke
Thrombolysis with intravenous t-PA is first-line
treatment for acute ischemic stroke. Major clinical
trials of thrombolysis in patients with ischemic
stroke did not exclude patients with dissection,
and a meta-analysis suggested no difference in
the risk of hemorrhage in patients with dissec-
tion and in those without dissection.21,22 Intra
venous t-PA can be efficacious if it is adminis-
tered within 4.5 hours (or perhaps even longer)
after symptom onset in selected patients,23-27 but
the Food and Drug Administration has not yet
approved its use beyond a 3-hour window. At this
hospital, patients give informed consent for the
administration of intravenous t-PA within 4.5 hours
after symptom onset, on a case-by-case basis.
However, patients are ineligible if they do not
know the time of symptom onset or if their pre-
sentation is delayed because of neurologic symp-
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toms (e.g., in this case, the patient fell back to
sleep, possibly because of brain-stem ischemia
that decreased consciousness). In patients with
basilar-artery thrombosis with severe disability,
such as those with the locked-in syndrome,
intraarterial thrombolysis or clot retrieval can
be performed up to 24 hours after symptom on-
set. Ongoing clinical trials and innovative tech-
nology may help to widen the therapeutic win-
dow, and educating primary care providers to
recognize early stroke symptoms can also be
very useful.28-31
In the acute care setting, patients with large-
territory cerebellar or cerebral infarcts should be
monitored in the neurologic intensive care unit
for edema and herniation. Treatment can involve
intravenous hyperosmolar therapy, placement of
an external ventricular drain for hydrocephalus,
or decompressive craniectomy.32
Treatment for dissection in patients who are
not receiving acute care should be individualized.
It may seem risky and counterintuitive to admin-
ister anticoagulation therapy for a torn blood
vessel, but cerebrovascular dissections are rarely
actual ruptures of the vessel; more often, they
are separations of the intima from the rest of the
vascular wall, and the prothrombotic intimal flap
can act as a source of distal emboli. Patients with
dissection within the intradural portion of the
vertebral artery (Fig. 1A) who receive anticoagu-
lation therapy are at increased risk for bleeding;
unless a clot is advancing toward the basilar
artery, anticoagulation therapy is not recom-
mended. On rare occasions, dissection occurs
within the tunica media or adventitia, resulting
in a pseudoaneurysm or vessel-wall rupture and
subarachnoid hemorrhage33,34; this is more com-
mon in posterior-circulation intracranial dissec-
tions and spontaneous dissections associated
with collagen vascular disease (e.g., Marfans
syndrome and fibromuscular dysplasia). This pa-
tient does not have marfanoid features. Our over-
all clinical experience indicates that the risk of
hemorrhage is relatively low among patients with
arterial dissection.35 Unless there is evidence of
subarachnoid hemorrhage or extensive intracranial
vertebral-artery dissection with the formation of a
pseudoaneurysm, careful anticoagulation therapy
for 3 to 6 months, to give injured vessels a chance
to recanalize, can maximize the riskbenefit ratio
1745
 The n e w e ng l a n d j o u r na l of m e dic i n e

for this patient, because the chance of emboli is individualized medical management. For exam-
highest within the first few months. ple, low-density lipoprotein (LDL) cholesterol
levels below 70 mg per deciliter (1.8 mmol per
Workup for Stroke and Secondary Prevention liter) are associated with a significant decrease
Table 3 lists indications for studies that should in the risk of stroke; however, substantially lower
be tailored to the individual patient. Patients with LDL cholesterol levels (i.e., 30 mg per deciliter
multiple cardiovascular risk factors can have mul- [0.8 mmol per liter]) are associated with an in-
tiple simultaneous causes of stroke. As the popu- creased risk of intracranial hemorrhage.36 Life-
lation lives longer and ages better, causes of stroke style modifications (e.g., healthful changes in diet,
normally associated with younger age groups exercise, and alcohol consumption, as well as smok-
(e.g., traumatic dissection and patent foramen ing cessation) and the treatment of obesity and
ovale) are affecting older patients; for example, sleep apnea are also important. Supervised neuro-
paradoxical embolism can be caused by deep-vein rehabilitation is crucial for recovery,37 and treat-
thrombosis after hip replacement, or vertebral- ment of depression and anxiety can improve
artery dissection can be caused by traumatic neck motor outcomes after stroke.38
injury in patients, such as this one, with spinal In summary, stroke often has multiple mech-
arthritis. anisms, and thus a thorough, individualized
Understanding the cause of the initial stroke workup ensures a comprehensive strategy for
is the best way to prevent recurrence. In this treatment and prevention.
case, it is important to understand the course of Dr. Rosenberg: Dr. Kim, would you tell us what
the vertebral artery as it travels within the cervi- happened with this patient?
cal spinous processes (Fig. 1A). The elbow of Dr. Kim: The patient was admitted to the
the artery (Fig. 1A, segment III) is likely to tear neurology service. Anticoagulation therapy
during rotation of the joint at the level of C1 and with heparin was begun and was later transi-
C2. In addition to dissection, older patients with tioned to warfarin. His symptoms gradually
cervical arthritic lesions can undergo the devel- improved, and he was discharged on the fourth
opment of bow-hunters syndrome, which oc- hospital day. Results of a cardiac ultrasound
curs when extreme rotation of the neck (such examination and routine laboratory studies
as the rotation that occurs during archery) oc- were normal. There were no arrhythmias on
cludes a vertebral artery in the neck and the 24-hour Holter monitoring. Two months after
other vertebral artery is already atretic or oc- discharge, a CT angiogram showed persistent
cluded (Fig. 1D). Exercise has benefits that nonvisualization of the cervical portion of the
generally outweigh the risks, but the patient left vertebral artery and better visualization of
should be counseled about bow-hunters syn- the intradural portion; anticoagulation therapy
drome and the risk of vertebral-artery dissec- was continued, with the plan to perform repeat
tion. Dynamic transcranial Doppler ultraso- imaging in 3 months. Seven months after dis-
nography to monitor intracranial flow during charge, a repeat CT angiogram showed persis-
head turning can gauge limits in range of mo- tent nonvisualization of the cervical portion of
tion. If the transcranial Doppler study shows the left vertebral artery on early-phase images
poor flow and the patient becomes symptom- but full opacification of the cervical portion on
atic during movement, then an intervention, delayed images, with focal areas of luminal
such as a neck brace to limit range of motion thrombus that were most prominent at the
or possibly stenting, may be indicated. level of C4 and C5. The intradural left vertebral
artery and the dominant right vertebral artery
Modification of Risk Factors were patent. His symptoms had completely re-
Since an individual patient can have overlapping solved, and he was back to performing high-
causes of stroke, lifestyle modifications and the level physical activities. The decision was made
management of all risk factors (e.g., hyperten- to discontinue warfarin, and he resumed tak-
sion, diabetes, physical inactivity, and obesity) ing aspirin for secondary stroke prevention.
are keys to secondary stroke prevention.15,16 Af- Careful control of his blood-pressure and lipid
ter epithelial injury due to dissection, the risk of levels has been maintained.
atherosclerosis at the site of the injury becomes Dr. Rosenberg: Are there questions for any of
higher. Monitoring blood markers is helpful in the discussants or the patient?

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 case records of the massachuset ts gener al hospital

A Physician: Dr. Ning, would you have initiated
treatment with intravenous t-PA if the patient
had arrived within the 3-hour window?
Dr. Ning: I would have administered intra
venous t-PA within 3 hours (or even 4.5 hours)
after arrival if a CT scan showed no evidence of
hemorrhage. Patients who receive intravenous
t-PA are 30% more likely to have better outcomes
at 3 months39; however, t-PA can trigger reperfu-
sion injury37-40 and result in symptomatic intra
cerebral hemorrhage in 3.3 to 15.7% of patients.41-44
Continuing clinical and translational research re-
garding the timing of stroke and the widening
of therapeutic windows for the administration of
thrombolysis is important.23,29,30,37,40,45,46
A Physician: Swimming the freestyle stroke
involves a lot of head turning. Were you advised
to stop swimming freestyle after your stroke?
The Patient: After my stroke, I was advised
not to swim at all. I turned to other types of
activity, including walking and running. After
about 1 year, I resumed swimming and have
had no further problems.
A nat omic a l Di agnosis
Dissection of the left vertebral artery and cerebel-
lar infarction.
This case was presented at the postgraduate course Primary
Care Internal Medicine Principles and Practice 2011 (directed by
John D. Goodson, M.D., Charles J. Hatem, M.D., Richard J. Pels,
M.D., and Jennifer E. Potter, M.D., and sponsored by the Har-
vard Medical School Office of Continuing Education).
No potential conflict of interest relevant to this article was re-
ported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Drs. John Goodson, Stephen Parker, Thomas Byrne,
David McMullin, Su-Yu Xu, Ferdinando Buonanno, Eng H. Lo, and
Pei-Chen Ning for providing guidance for the conference and
manuscript, and the patient for his participation in the conference.

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