ORIGINAL CONTRIBUTION

Multiple Brain Infarcts and Balint Syndrome
in Aortic Arch Angiosarcoma
Iris Ben-Bassat Mizrachi, MD, Jonathan D. Trobe, MD, Michael G. Deeb, MD,
Stephen R. Ramsburgh, MD, David M. Williams, MD, and Stephen S. Gebarski, MD
Abstract: A 50-year-old woman presented with
subacute cognitive decline, impaired eye movements,
and simultanagnosia, components of the Balint syndrome. She had relatively low blood pressure in the
left arm and left finger clubbing. Brain imaging identified multiple acute infarcts. Transesophageal echocardiography showed no cardiac abnormalities but
demonstrated a thickened aortic wall and an intraluminal aortic arch mass. The surgical specimen
revealed angiosarcoma. Of the few reported angiosarcomas involving the aorta, most have been located
in the abdominal segment. This is only the second
reported case of aortic arch sarcoma presenting with
stroke.
(J Neuro-Ophthalmol 2006;26:107–112)

A

ortic arch disease is a rare cause of stroke. When stroke
does occur, it usually results from calcific atherosclerosis (1,2), or much less commonly, from Takayasu aortitis
(3,4). We report a patient who had multiple brain infarcts
that manifested as the Balint syndrome. In the course of
cardiac imaging, a lesion of the aortic arch was demonstrated. The surgical specimen revealed extensive angiosarcoma involving the aortic arch and origins of the great
vessels. We believe this to be only the second case in which
aortic arch sarcoma has presented with stroke.

CASE REPORT
A 50-year-old-woman presented with progressive
visual problems and cognitive deterioration over a period of
Department of Ophthalmology (IB-BM, JDT), W.K. Kellogg Eye
Center, and Departments of Neurology (JDT), Surgery (MGD), Pathology
(SRR), and Radiology (DMW, SSG), University of Michigan, Ann Arbor,
Michigan.
Address correspondence to Iris Ben-Bassat Mizrachi, MD, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel 52621;
E-mail: irismizrachi@yahoo.com
Supported in part by a fellowship from the American Physician
Fellowship for Medicine in Israel.

J Neuro-Ophthalmol, Vol. 26, No. 2, 2006

three months. She reported difficulty finding and identifying objects. Her son reported that she had displayed increasing confusion, inertia, and untidiness. There had been
a 40-lb weight loss over a three-month period. Six months
earlier, she had successfully driven a public bus and negotiated the purchase of a house. She had polycystic kidney
disease and was a heavy cigarette smoker.
Blood pressure was 162/81 in the right arm, 78/63 in
the left arm; radial and ulnar pulses in the left arm were
thready. Clubbing of the fingers of the left hand was marked
(Fig. 1).
She knew the year but not the day of the week and
could not name the city or the hospital. She could not follow three-step commands and was flawed in object naming.
Visual acuities were 20/20 in both eyes, pupil size and
reactivity were normal, and ophthalmoscopy was normal.
There was a complete right homonymous hemianopia to
confrontation. Saccades to command and pursuit eye movements were markedly reduced in amplitude in all directions,
but spontaneous saccades were full. She could not interpret
magazine action photographs. She consistently misreached
toward the left when instructed to touch external objects but
did not misreach in touching her own body parts. Motor
examination was otherwise normal. Sensory and reflex
examinations were normal.
MRI (Fig. 2) demonstrated an extensive area of high
signal in the left parieto-occipital region on T2 and FLAIR
sequences. Restricted diffusion was present in that region.
There were smaller areas of restricted diffusion in the left
cerebellar hemisphere, the thalamus bilaterally, and the periventricular white matter bilaterally. There was a small area
in the right parieto-occipital region with high signal on T2
and FLAIR sequences but without restricted diffusion,
suggesting an older infarct. A high-signal lesion above the
left centrum semiovale on a pre-contrast T1 sequence was
initially interpreted as consistent with a hemorrhagic infarct.
Brain magnetic resonance arteriography (MRA) showed no
significant large artery disease.
Standard serum chemistries were normal, and a
workup for hypercoagulability and inflammatory processes
was negative except for an erythrocyte sedimentation rate
of 105 mm/h and a C-reactive protein level of 5.4 mg/dl

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Mizrachi et al

FIG. 1. A. Normal right hand.
B. Clubbing of the fingers of the left
hand.

(normal, 0.0–0.6 mg/dl). Lumbar puncture revealed a normal
opening pressure and glucose level (57 mg/dl). The protein
level was mildly elevated at 51 mg/dl (normal, 15–45
mg/dl); cytology and flow cytometry were normal.
Because multiple acute brain lesions were demonstrated on imaging, a cardiac source of emboli was sought
in a transesophageal echocardiogram (TEE). The heart images
were normal, but there was a large multilobulated soft tissue
mass occupying approximately 50% of the aortic arch

lumen with a smaller mobile component in the proximal
descending thoracic aorta (Fig. 3).
CT and computed tomographic angiography (CTA)
(Fig. 4) of the neck, thorax, and abdomen demonstrated
enhancement of a thickened aortic arch wall extending to
the origin of the left subclavian artery. In the superolateral
portion of the aortic arch, there was a focal irregularity
suggestive of an intraluminal mass extending into the
innominate and common carotid arteries and causing

FIG. 2. Brain MRI. A. Axial T2
images show lesions in both cerebral
hemispheres. The left fronto-parietal
lesion shows sulcal flattening,
suggestive of recent infarct (large
arrow). The right parieto-occipital
lesion shows focal loss of brain substance suggestive of an older infarct
(small arrow). B. Axial diffusionweighted imaging at the same level
shows restricted diffusion in the left
cerebral lesion consistent with recent
infarct (large arrow). The right hemispheric lesion shows no restricted
diffusion (small arrow). C. Axial precontrast T1 image above the centrum semiovale shows a high-signal
lesion in the left frontal lobe consistent with subacute hemorrhage
(arrow). D. Axial post-contrast T1
image at the same level shows
nodular enhancement (small arrow)
posterior to the hemorrhage (large
arrow), suggesting metastasis.

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Aortic Arch Angiosarcoma

FIG. 3. Transesophageal echocardiogram demonstrates
a mass in the wall and lumen of the aortic arch (arrow).

complete occlusion of the left subclavian artery. The other
large vessels in the chest and abdomen appeared normal.
The kidney and liver showed multiple cysts consistent with
the history of polycystic kidney disease, and there was
a wedge area of low attenuation in the spleen suggestive of
an infarct. Arch and neck MRA demonstrated similar findings but did not show the mass as well as did CT and CTA.
These radiographic and clinical findings raised the
suspicion of Takayasu aortitis or severe atherosclerosis.
Given the protracted clinical course, constitutional symptoms, weight loss, and elevated acute phase reactants, the
diagnosis of aortitis was favored. The patient was treated
with prednisone 60 mg/d and heparin 24,000 units/d.

J Neuro-Ophthalmol, Vol. 26, No. 2, 2006

On the tenth hospital day, she became more confused
and less responsive. Although brain imaging failed to disclose new findings, she was taken for surgical replacement
of the aortic arch, including the proximal descending aorta,
innominate artery, and carotid arteries with a Hemashield
graft (Boston Scientific, Wayne, NJ), together with ligation
and oversewing of the left subclavian artery. At surgery, the
aortic arch was indurated, thickened, and adherent to the
surrounding soft tissues.
Gross pathology (Fig. 5A) demonstrated a firm, thickened aortic wall with severe atherosclerosis and occlusion
of the proximal subclavian and partial occlusion of the
innominate and left common carotid arteries by necrotic
tumor and thrombus. Histopathology of the aortic arch and
large vessels demonstrated intraluminal tumor with obvious
invasion of the vessel wall and extensive necrosis. The
neoplastic cells were pleomorphic, spindled, and epithelioid, with hyperchromatic nuclei and abundant eosinophilic
cytoplasm. Occasional mitotic figures were seen. In some
areas of the tumor, the cells were arranged in rudimentary
vascular channels (Fig. 5, B and C). Immunohistochemical
staining was positive for CD31 antibody, an endothelial
marker (Fig. 5D). The pathologic diagnosis was high-grade
angiosarcoma with thrombus and atheroma.
Because of the patient’s general ill health, adjuvant
oncologic treatment was deferred. A follow-up CT scan
three weeks later disclosed a new pancreatic lesion believed
to be a metastasis. The patient died four months after presentation. An autopsy was not performed.

DISCUSSION
Our patient presented with stepwise neurologic and
cognitive deterioration over a period of three months. Neurologic examination consisted of volitional gaze paresis,

FIG. 4. Aortic imaging. A. Coronal reformatted magnetic resonance angiography of the aortic arch and neck vessels shows
irregular stenosis at the origin of the left common carotid artery (large arrow) and ill-defined signal inhomogeneity of the
superior aspect of the aortic arch (small arrows). The left subclavian artery is not seen. B. Computed tomographic
angiography (CTA) axial source image shows irregular luminal narrowing of the left common carotid artery origin (arrows)
and, less so, of the innominate artery origin. C. CTA axial source image at a level below that of (B) shows a bulky irregular
intraluminal soft tissue mass that spreads along the aortic arch superiorly, invading the aortic wall and nearby tissues (arrows).

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FIG. 5. Pathology of surgical specimen. A. Gross pathology shows narrow and thickened aortic arch superiorly with
occlusion of the left subclavian artery (large arrow), partial occlusion of the left common carotid artery (small arrow), and
a patent innominate artery (asterisk). B. Histopathology demonstrates intraluminal tumor with invasion of the vessel wall
(arrow) (hematoxylin and eosin stain, x10). C. Pleomorphic spindled (white arrowhead) and epithelioid (black arrowhead)
cells containing abundant eosinophilic cytoplasm and occasional mitotic figures (white arrow). In some areas of the
tumor, the cells are arranged in rudimentary vascular channels (black arrow) (hematoxylin and eosin stain, x40).
D. Immunohistochemical stain for CD 31, an endothelial marker, is positive (brown staining).

misreaching only under visual guidance, and simultanagnosia, features of Balint syndrome. Brain imaging showed
a large new left parieto-occipital infarct and smaller new
infarcts in the left cerebellar hemisphere, thalamic nuclei,
and periventricular white matter. The multiplicity of fresh
brain infarcts led to a search for a cardiac source of emboli,
but the heart was normal. Instead, TEE and chest imaging
surprisingly disclosed an aortic arch lesion, a finding we
should have suspected because of the relatively low blood
pressure recorded in the left arm and the dramatic left finger
clubbing. At the time of surgical revascularization, the
lesion proved to be an angiosarcoma with atherosclerotic
occlusion of the great vessels.
Angiosarcomas are rare malignant tumors that
recapitulate many of the functional and morphologic
features of normal endothelium (5). They vary from highly

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differentiated tumors that resemble hemangiomas to those
with severe anaplasia. Most angiosarcomas have a predilection for skin, muscle, and bone, but they may occur at
any location in the body and rarely arise from major blood
vessels. Of the 21 reported cases of aortic angiosarcoma
(6), most have involved the abdominal aorta, with only five
involving the aortic arch, as in our patient.
A comprehensive review of the 180 reported cases of
malignant tumors of the aorta (7) revealed that angiosarcoma makes up a small fraction (Table 1). Among these
180 cases, 50 were mural tumors originating in the adventitia and media and 130 were luminal tumors originating
in the intima. Among those of intimal origin, 28 cases
were differentiated sarcomas, including myxofibrosarcoma,
leiomyosarcoma, angiosarcoma, myxoid chondrosarcoma,
hemangioendothelioma, and undifferentiated pleomorphic
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TABLE 1. Primary malignant tumors of the aorta*
Tumor type
Mural tumors (media/adventitial origin)
Luminal tumors (intimal origin)
Differentiated
Myxofibrosarcoma
Leiomyosarcoma
Angiosarcoma
Myxoid chondrosarcoma
Hemangioendothelioma
Undifferentiated pleomorphic sarcoma
Undifferentiated
Uncertain morphology

No. of reported cases (n = 180)
50
130
28
16
2
2
1
2
5
81
21

*From Reference 7.

sarcoma; 81 were undifferentiated intimal sarcomas; and 21
cases were of uncertain histologic morphology and
location. In this comprehensive review (7), the authors
questioned the pathologic diagnosis of some of the reported
cases of intimal origin and redefined them as undifferentiated angiosarcoma.
Because primary aortic arch tumors comprise a wide
range of histologic entities (7,8), histopathology and adjunctive immunohistochemistry are critical in diagnosis,
particularly in poorly differentiated forms in which endothelial differentiation is difficult to identify (5,9,10). Angiosarcoma usually expresses endothelial antigens, including
von Willebrand Factor, CD31, and CD34. Although von
Willebrand Factor, which was not tested in our case, is the
most specific vascular marker, its sensitivity is very low and
it often produces weak staining. Staining for CD31, which
was positive in our case, combines relatively high specificity and sensitivity, being positive in approximately 90%
of angiosarcomas (7,11–13).
The clinical presentation of angiosarcoma of large
vessels includes weight loss, fever, elevated acute-phase reactants (14), and manifestations of tumor or platelet emboli to
the abdominal viscera, bone, skin (14), or brain (15). Stroke
as the presentation of aortic arch sarcoma has been reported
only once before (16). That patient had expressive aphasia
and right hemiparesis caused by left middle cerebral artery
infarct (and reduced left arm blood pressure, as our patient
had). That case emphasized the aortic arch imaging features
but did not provide details of the pathology or brain imaging.
An additional single case report described a middle cerebral
artery stroke from a carotid artery angiosarcoma (17).
Our case underscores the importance of highdefinition imaging of the thorax in the diagnosis of aortic
arch disease. In the past, most large vessel sarcomas were
diagnosed after embolectomy or on autopsy. In a compre-

hensive review of cases reported until 1998 (8), more than
half of the 87 aortic tumors were discovered at autopsy. In
a 1990 review of pulmonary artery sarcomas (18), 56 (60%)
of 93 patients were diagnosed at autopsy. On the other hand,
a 1997 review (19) found that 38 (90%) of 42 cases of
pulmonary artery sarcoma were diagnosed at antemortem
examination. The authors attributed the antemortem diagnosis to the use of MRI, which demonstrated three differentiating features: 1) enhancement of the vessel wall and
mass, a finding not seen in thrombus (20,21); 2) a vessel
distended by a soft tissue mass or extravascular spread,
findings characteristic of a tumor; 3) lack of abrupt luminal
narrowing, a finding characteristic of embolus. MRA can
show the arterial narrowing and irregularity, but CT, CTA,
and MRI can demonstrate the irregular lumen, the intraluminal mass, and the invasion of the vessel wall and surrounding tissues. Conventional angiography is not favored
in evaluation of angiosarcoma because of the risk of embolic spread of tumor (16).
There are no meaningful guidelines as to treatment of
angiosarcoma because the condition is so rare. Surgical resection of the tumor-bearing aortic region with graft interposition is the standard therapy, although endarterectomy
without resection might be equally effective in intimal sarcomas, in which the malignant cells are limited to the luminal
surface (6). Adjuvant chemotherapy (doxorubicin and ifosfamide) has been used palliatively for embolic, metastatic, or
non-resectable tumors. In a report of 21 patients with the aortic
angiosarcoma (6,8), the mean survival rate was 13 months.

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