Stroke
ILLUSTRATIVE TEACHING CASE
Section Editors: Sophia Sundararajan, MD, PhD, and Alexis Simpkins, MD, PhD, MSCR

Cardiac Myxoma Embolization Causing Ischemic
Stroke and Multiple Partially Thrombosed
Cerebral Aneurysms
Praveen Kesav, DM; Seby John, MD; Priti Joshi , MD; Waqar Haider Gaba , Syed Irteza Hussain , MD

A
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31-year-old male of South Asian origin, with no
known vascular risk factors, presented for evaluation
of acute onset impaired comprehension and slurring
of speech. He also reported holocranial headaches of 2
weeks duration with no telltale features of raised intracranial pressure. No other focal neurological symptoms
or systemic symptoms of concern were noted. Physical examination revealed right-sided upper motor neuron facial paresis, nonfluent aphasia, and dysarthria. His
baseline National Institutes of Health Stroke Scale score
was 4. No signs of meningeal irritation were noted. Noncontrast computerized tomography of the head revealed
a hypodensity in the left temporoparietal region suggestive of an acute infarct, along with chronic infarcts in the
right cerebellum, right parietal lobe, and left thalamus.
In addition, multiple hyperdense areas (largest being in
the left perisylvian region) were observed in the supratentorial regions as well (Figure 1A and 1B). Computed
tomography angiography of intracranial vessels followed
by conventional digital subtraction cerebral angiography revealed multiple dysplastic/fusiform aneurysms, 3
involving the right pericallosal artery, 2 involving the distal
right middle cerebral artery M4 branches, and 1 involving
the right callosomarginal artery (Figure 1C). The inferior
branch of the left middle cerebral artery was dysplastic
with a partially thrombosed proximal aneurysm and a distal fusiform aneurysm (Figure 1D). Contrast-enhanced
magnetic resonance imaging of the brain confirmed
the presence of an acute left middle cerebral artery
infarct and multiple aneurysms, with the largest being

a partially thrombosed aneurysm in the left sylvian fissure measuring 13 mm (Figure 2A through 2D). There
were no parenchymal structural lesions or macro hemorrhages. Hematology investigations were unremarkable. A transthoracic echocardiogram was performed,
which revealed a large mobile mass measuring 1.8×3.1
cm with calcific rim and echo lucent space in its substance, attached on the atrial side of the anterior mitral
valve with limited attachment on the interatrial septum.
No evidence of systolic dysfunction was observed. The
differential diagnosis entertained in view of the clinical,
neuroimaging, as well as cardiac imaging findings were
intracardiac tumor-like myxoma versus infective or noninfective endocarditis. In view of the high-risk cardioembolic source, patient was deemed to be a candidate for
early surgical resection of the cardiac lesion, which was
duly performed within a week of hospitalization. Postoperative histopathologic evaluation of the resected cardiac
pathology revealed features consistent with cardiac myxoma (Figure 3A and 3B). No intraoperative or postprocedural complications were noted. The cerebral aneurysms
being multiple, unruptured, and secondary to underlying
cardiac myxoma, were not subjected to open surgery or
endovascular embolization. Plan for potential combined
chemoradiotherapy and surgical intervention will be discussed based on findings of follow-up parenchymal and
angiographic studies. The patient was maintained on single antiplatelet agent for secondary stroke prophylaxis,
with advice for speech and language rehabilitation for his
residual neurological deficits.

Key Words: dysarthria ◼ headache ◼ male ◼ risk factors ◼ speech
Correspondence to: Syed Irteza Hussain, MD, Neurological Institute, Cleveland Clinic Abu Dhabi, PO Box 112412, Al Maryah Island, Abu Dhabi, UAE. Email hussais3@
clevelandclinicabudhabi.ae
For Sources of Funding and Disclosures, see page e13.
© 2020 American Heart Association, Inc.
Stroke is available at www.ahajournals.org/journal/str

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DISCUSSION
Cardiac myxoma is the most common primary cardiac
tumor, accounting for up to 80%, with an estimated
annual incidence of 0.5 per million population per year.1–3
More than 80% of cardiac myxomas arise from the left
atrium,2 with multitude of presentations in the form of
cardiac obstructive symptoms, embolization (cerebral
and/or systemic) as well as constitutional symptoms.1–3

Fifty percentage of cardiac myxoma patients present
with symptoms related to mitral valve obstruction (dyspnea, dizziness, palpitations, and congestive heart failure)
and can occur in up to 70% of them during the natural
course of the illness.2 Constitutional symptoms in the
form of fever, weight loss, and fatigue may occur in about
58% of those with cardiac myxoma. Systemic embolization can be noted in one-third of cases at any time during the course of the illness.1–3 Neurological symptoms

Figure 2. Contrast-enhanced magnetic resonance imaging brain.
Contrast-enhanced magnetic resonance imaging brain showing (A) isointense circumferential lesions on left (thick arrow) and right sylvian fissure
(thin arrow) on precontrast T1 axial images. B, T2 axial sections reveal hypointense signal on the left sylvian fissure (thick arrow), mixed intense
signal on the right sylvian fissure (thin arrow). The lesion in left sylvian fissure is hypointense on susceptibility weighted sequences (C; thick arrow)
and exhibits circumferential enhancement of the vessel wall involving the left middle cerebral artery (MCA) in the sylvian fissure (D; thick arrow), with
nodular enhancement on right side (D; thin arrow) on contrast-enhanced T1 coronal sequences. The imaging findings on the left sylvian fissure is
consistent with a partially thrombosed aneurysm involving the posterior insular branch of the left MCA. In addition, there is evidence of acute infarct
involving the left MCA territory (B; star).
Stroke. 2021;52:e10–e14. DOI: 10.1161/STROKEAHA.120.031679

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Illustrative Teaching Case

Figure 1. Noncontrast computerized
tomography.
Noncontrast computerized tomography
head showing multiple hyperdense
lesions on axial images (A) in the left
sylvian fissure (thick arrow); right sylvian
fissure (A; thin arrow) as well as in the
left posterior subcortical frontal region (B;
thin arrow). C, Invasive cerebral angiogram
of right internal cerebral artery depicting
fusiform aneurysms involving the right
callosomarginal artery (arrow head),
pericallosal artery (star and thick arrow), as
well as middle cerebral artery (MCA; thin
arrow). D, Lateral projection views of left
internal cerebral artery depict dysplastic
inferior branch of MCA with a partially
thrombosed aneurysm (thin arrow), as well
as a distal fusiform aneurysm (thick arrow).

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Illustrative Teaching Case

have been documented in about 26% to 45% of cardiac myxomas.2 Cerebral embolization may present commonly as ischemic infarcts1,2 and rarely with myxomatous
intracranial aneurysms, brain parenchymal myxomatous
metastases, as well as intracerebral hemorrhage.3–5
Transthoracic echocardiography gives the initial clue
toward the presence of a cardiac mass, with transesophageal echocardiogram) providing further details about
the location as well as mobility, especially for small-sized
lesions and biatrial multiple cardiac tumors.6,7 However,
neither of the abovementioned techniques are helpful to
differentiate cardiac myxomas from other cardiac tumors
as well as intracardiac thrombi.7 Multimodality imaging in
the form of contrast-enhanced cardiac magnetic resonance imaging has played a vital role in reliably diagnosing cardiac myxomas preoperatively. Cardiac myxoma
exhibits T1 heterogenous hypointensity relative to the
myocardium, T2 hyperintensity, as well as heterogenous
contrast enhancement on magnetic resonance imaging,
which are unique to myxoma compared with other primary
cardiac tumors or cardiac thrombus.7 Surgical resection
is the definitive treatment option for cardiac myxoma, as
medical management even with anticoagulant therapy
has been proven ineffective to prevent recurrent embolic
events.2,6 As development of embolic phenomenon as
well as sudden cardiac death occur in ≈10% of patients

awaiting surgery, cardiac myxomas should be considered
a surgical emergency, with avoidance of potential delays
in those without any obvious surgical contraindications.6,7
Despite the lack of global consensus about the ideal
surgical procedure for cardiac myxoma resection, the inhospital mortality related to surgery seldom exceeds 3%
as per available literature evidence,6 thereby contributing to excellent early and mid-term results if resected
promptly. Antiplatelets as well as anticoagulants (Warfarin) have been traditionally used for secondary stroke
prophylaxis, both pre- and postcardiac myxoma resection
(for a variable duration), with no clear available evidencebased guidelines or recommendations as of now.1,2
To date, there are fewer than 60 published cases
of cerebral myxomatous aneurysms in literature, the
first being in 1966,2,8 with partially thrombosed ones
being rarer. Rarity of this entity has contributed to lack
of knowledge about the natural course of evolution of
cerebral myxomatous aneurysms, in turn leading to
lack of definite management guidelines as well.8–10 Our
patient was unique in that he had simultaneous neuroimaging evidence of both manifestations of myxomatous cerebral embolization, which include the commoner
ischemic infarct as well as the less common myxomatous aneurysms.3 The latter is more often reported as
a delayed complication of cardiac myxoma with mean
duration between tumor resection and aneurysm detection varying between 2 and 300 months.3,4,8 A review of
37 published cases of myxomatous aneurysms revealed
the median age of 38 years (range, 10–69 years), with
female:male ratio of 2.7:1.10 These aneurysms are usually multiple, of fusiform/saccular morphology and have
predilection for distal branches of middle cerebral arteries.2,3 Advancements in neuroimaging modalities have
contributed to better delineation and identification of
both myxomatous aneurysms as well as myxomatous
metastases.4,5 On noncontrast computerized tomography
brain, these myxomatous aneurysms seem hyperdense,
on account of accumulation of myxoid matrix or calcification in the aneurysmal wall.10 Although the exact mechanism of development of myxomatous aneurysms is still
enigmatic, the most plausible and accepted one is the
metastasize and infiltrate theory, whereby the myxoma
fragments embolize from the heart, seed in the cerebral vessel wall, initiate an inflammatory cascade, in-turn
leading to dilatation and aneurysm formation.1–3,8,10 High
levels of interleukin-6 in the CSF produced by the cardiac myxoma cells contribute to upregulation of MMPs
(matrix metalloproteinases), which in turn promotes degradation of extracellular matrix and myxoma invasion
into the walls of cerebral arteries, ultimately resulting in
aneurysm formation.3,10 This theory is substantiated by
demonstration of proliferation of myxomatous cells in the
aneurysmal wall as well as the invasion of internal elastic
lamina.10 An alternative less known hypothesis for myxomatous aneurysm pathogenesis is the vascular damage

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Figure 3. Hematoxylin and eosin staining.
Hematoxylin and eosin staining of the resected tissue (A) on low
power view shows blue background of acid mucopolysaccharides
with mesenchymal cells (depicted in green circles), with high power
view (B) demonstrating round, plump, and stellate mesenchymal cells
consistent with cardiac myxoma.

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• Cardiac myxoma is the most common primary cardiac tumor and are notorious for both early as well as
delayed neurological manifestations.
• Ischemic stroke is the most common neurological
manifestation of cardiac myxoma, with up to 0.5% of
all ischemic strokes being attributed to myxomatous
embolization.
• Myxomatous aneurysms and myxomatous cerebral
metastases are rarer neurological complications of

cardiac myxomas, with putative pathological mechanism being metastasize and infiltrate theory.
• Mobility rather than size of the cardiac myxoma determines the embolization potential.
• Concomitant ischemic strokes and cerebral aneurysms
should make one suspect the possibility of the underlying cardiac myxomas, despite being a rare entity.

theory, whereby the postembolic vascular damage and
subsequent endothelial scarring contributes to hemodynamic alteration in cerebral vascular dynamics resulting
in aneurysm formation.10
On account of the rarity of the cases, little is known
about the natural history of myxomatous aneurysms. A
meta-analysis of 37 published cases of myxomatous
aneurysms highlighted that 78.4% of them were managed conservatively, with 75.9% among them demonstrating stability or regression on follow-up imaging
studies.10 Hence for unruptured myxomatous aneurysms,
majority of the researchers propose conservative management, with serial angiographic studies on follow-up
(initially at 3 months and later on at 6–12 months interval
as per stability), to look for interval change, especially any
enlargement. About 20.7% cases in the study by Zheng
et al10 demonstrated enlargement on follow-up angiographic studies, with all-cause mortality being 3.4%.
However, there is paucity of data about the risk of rupture of cerebral myxomatous aneurysms in literature on
account of rarity of cases. The risk of rupture of primary
intracerebral aneurysms cannot be extrapolated to cerebral myxomatous aneurysms on account of the different
respective pathological mechanisms involved.
There are isolated published reports pertaining to the
role of microsurgical resection/endovascular coiling,8 chemotherapy, and radiotherapy9 in management of myxomatous aneurysms, although a definitive guideline is still
lacking. In case of ruptured or enlarging aneurysm, decision to treat should be made on a case by case basis.
Given that aneurysms related to cardiac myxoma are multiple, and often times involve terminal intracerebral vessels,
both open microsurgical and endovascular techniques
have their limitations and may not assure a complete cure.
Open microsurgery may include resection or trapping of
the aneurysm. Application of clips may not be feasible
given the friable nature of the vessel wall. Standard endovascular coil embolization techniques are not possible
given the fusiform nature of these aneurysms in majority
of cases. In addition, invaded tumor cells in the vessel wall
remain unattended in endovascular treatments, thereby
potentially contributing to further invasion as well as
recurrence.8 There is lack of evidence for antithrombotic

medications in management of thrombosed cerebral
myxomatous aneurysms especially after resection of the
cardiac myxomas. As there is histopathologic evidence of
actively proliferating tumor cells in the myxomatous aneurysmal wall, chemotherapy (doxorubicin/etoposide/carboplatin) as well as radiotherapy have also been documented
to be effective in individual cases.9,10
On account of multiple fusiform aneurysms with
no foci of active hemorrhage on imaging, our patient
is being planned for follow-up vascular imaging in 3
months to assess for any interval evolution, with potential for microsurgical resection with bypass of the largest
aneurysm (left perisylvian middle cerebral artery) along
with chemoradiotherapy in case of any lesion enlargement or new focal neurological symptoms.

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CONCLUSIONS
Cardiac myxoma may manifest de novo with neurological
symptoms, with ischemic strokes being the most common presentation and myxomatous aneurysms being
rarer. On account of the rarity of the latter, treatment
protocols are unclear and even surgical resection of
the primary cardiac tumor might not completely prevent
delayed occurrence of myxomatous aneurysms or myxomatous cerebral metastases.
ARTICLE INFORMATION
Affiliations
Department of Neurology, Neurological Institute (P.K.), Department of Neurology
and Neurointerventional Surgery, Neurological Institute (S.J., S.I.H.), Cleveland
Clinic Abu Dhabi, UAE. Cleveland Clinic Abu Dhabi, UAE (P.J.). Sheikh Khalifa
Medical City, Abu Dhabi, UAE (W.H.G.).

Sources of Funding
None.

Disclosures
None.

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TAKE-HOME POINTS

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Stroke. 2021;52:e10–e14. DOI: 10.1161/STROKEAHA.120.031679