CASE REPORTS

Multiple Intracranial Aneurysms as
Delayed Complications of an Atrial
Myxoma: Case Report
Walter C. Jean, M.D., Sabrina M. Walski-Easton, M.D.,
Eric S. Nussbaum, M.D.
Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota

OBJECTIVE AND IMPORTANCE: Atrial myxomas are rare cardiac tumors
that may cause neurological complications; however, delayed neurological events after total tumor resection are rare. In this report, we present
a patient who developed transient cerebral ischemic attacks and was
found to have multiple intracranial aneurysms 5 years after successful
resection of her atrial myxoma. At the time of myxoma resection, there
were no neurological symptoms; at the time of presentation with transient ischemic attacks, there was no evidence of atrial recurrence.
CLINICAL PRESENTATION: A 32-year-old woman presented with five episodes of right arm and face paresthesia, each lasting 15 to 20 minutes, 5
years after successful resection of her atrial myxoma. Clopidogrel bisulfate therapy was initiated, with resolution of her symptoms. Angiography
revealed multiple, peripherally located, fusiform cerebral aneurysms.
INTERVENTION: A left frontal craniotomy for resection and biopsy of one of
the aneurysms was performed, to establish the diagnosis. Pathological
analysis of the biopsied aneurysm provided evidence of direct atrial
myxoma invasion and occlusion of the cerebral blood vessel.
CONCLUSION: Neurological symptoms may accompany or lead to the
diagnosis of atrial myxoma. Rarely, as in this case, myxomatous aneurysms may develop years after definitive treatment of the primary tumor.
Patients who have undergone successful resection of a left atrial myxoma
may be at risk for delayed cerebral ischemia associated with aneurysm
development, and this phenomenon must be considered for patients with
neurological symptoms who present even years after myxoma removal.
The natural history, pathophysiological features, and treatment dilemma
of these aneurysms are discussed. (Neurosurgery 49:200–203, 2001)
Key words: Atrial myxoma, Embolism, Multiple fusiform aneurysms, Transient ischemic attacks

A

trial myxomas are rare tumors.
They reportedly occur in less than
0.05% of the population, but they constitute approximately 50% of primary
cardiac neoplasms (10, 14, 21, 22). These
tumors present with systemic embolization in up to 45% of cases (9, 14, 17, 22,
23), with the cerebral circulation being
involved in one-half of these instances

(9, 10, 14, 23). Cerebral ischemia resulting from direct tumor embolization is
the most common neurological presentation (1, 3, 4, 7, 11, 20). Other rare neurological manifestations include parenchymal brain metastasis (15, 19),
intracerebral hemorrhage (2, 7, 13, 23),
and oncotic aneurysm formation (2, 3,
5–8, 12, 14, 16, 18, 21, 22).

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With rare exceptions, neurological
symptoms related to atrial myxomas occur before or at the time of primary
tumor diagnosis. Reports of delayed
neurological symptoms after surgical
removal of the myxoma are sparse (7, 9,
14, 18, 20). We describe a patient who
presented with transient cerebral ischemic symptoms 5 years after complete
resection of a left atrial myxoma. A cerebral angiogram revealed numerous
fusiform intracranial aneurysms. The
pathophysiological features of these aneurysms and the symptoms of the patient are discussed, and the pertinent
literature is reviewed.

CASE REPORT
A 32-year-old, right-handed woman
was transferred to our institution after
experiencing five episodes of paresthesia involving the right arm and face.
Each event lasted 15 to 20 minutes and
resolved spontaneously, without residual symptoms. The neurological examination revealed no persisting deficits,
and a lumbar puncture disclosed no abnormalities. The clinical history of the
patient was significant for a left atrial
myxoma, which had been discovered 5
years earlier because of tumor embolization to the extremities and coronary
vessels. At that time, the patient had
undergone an uneventful thoracotomy,
with resection of the myxoma. Pathological analysis of the tumor revealed a
well-circumscribed mass measuring 3.5
⫻ 3.2 ⫻ 3 cm, with loose stroma and
scattered spindle-shaped cells. The patient had been without symptoms since
the time of surgery.
Ultrasonographic examination of the
carotid arteries and magnetic resonance
imaging of the brain were performed,
and findings were within normal limits.
Electroencephalography demonstrated
left temporal slowing, without epileptiform activity. Transthoracic echocardiography disclosed no evidence of a recurrent atrial myxoma, but four-vessel
cerebral angiography revealed multiple
peripheral, fusiform, intracranial aneurysms (Fig. 1).

Multiple Intracranial Aneurysms
The patient continued to experience
stereotypical episodes of right-sided
paresthesia. These symptoms ceased
with the institution of clopidogrel bisulfate therapy at 75 mg/d. To establish
whether there were active tumor cells
within the aneurysm walls, the patient
underwent a left frontal craniotomy for
resection of one of the aneurysms located at the frontal pole (Fig. 1). During
surgery, the aneurysm was noted to be
situated at a branch point in the vessel,
and one of the two efferent arteries was
observed to be thrombosed. The aneurysm was trapped between clips and
resected. Histopathological analysis revealed multifocal expansion of the vascular intima by the myxoid tumor,
which was characterized by a mucoid
matrix with stellate cells (Fig. 2). Disruption of the internal elastic lamina was
also observed.
The patient tolerated surgery well
and continued to receive clopidogrel
bisulfate, without additional symptoms.
Follow-up cerebral angiography performed 4 months after her neurological
presentation revealed no changes in the
remainder of her aneurysms.

DISCUSSION
Although neurological symptoms, especially transient ischemia, may accompany or actually result in the diagnosis
of left atrial myxomas, delayed neurological complications years after complete tumor excision are rare. Knepper
et al. (11) monitored eight patients for
up to 8 years after total excision of their
atrial myxomas, and none of the pa-

tients experienced subsequent neurological events. Similarly, of 35 patients
with atrial myxomas who were monitored at the Mayo Clinic, only 1 experienced cerebral ischemic symptoms 4
years after cardiac surgery (20). The timing of the neurological presentation in
our case is extremely unusual. In addition, the large number of peripheral aneurysms observed in this patient is striking. To our knowledge, there are fewer
than 15 cases in the literature in which
cerebral aneurysms associated with
atrial myxomas are described (2, 3, 5–8,
12, 14, 16, 18, 21, 22). The typical angiographic findings included peripherally
located, fusiform aneurysms (3, 5, 7, 8,
14, 18, 22). In our case, essentially all
major intracranial arteries distal to the
circle of Willis were involved.
The pathogenesis of these aneurysms
has not been definitively established. It
seems that the aneurysms result from
direct embolization of tumor material to
the intracranial vasculature, with tumor
cells lodging in the smaller, more peripheral arteries (5, 7, 8, 14). The cells
may then attach to the vessel wall,
weaken the endothelium, and invade
the internal elastic lamina. The disrupted vascular wall then dilates in an
aneurysmal manner. Pathological analysis of a biopsied aneurysm from our
patient revealed myxoid tissue occupying the lumen of the vessel, with invasion of the endothelium and disruption
of the internal elastic lamina. These
findings are consistent with the few previous reports in which pathological results were available (5, 7, 14).

FIGURE 1. Cerebral angiograms, indicating multiple fusiform aneurysms. A,
anteroposterior internal carotid artery injection. B, lateral internal carotid artery
injection.

Neurosurgery, Vol. 49, No. 1, July 2001

201

FIGURE 2. Intraoperative photograph
(A) and histopathological analyses (B
and C). A, fusiform aneurysm in situ.
The efferent artery (arrow) had spontaneously thrombosed because of luminal
occlusion by tumor cells. B, hematoxylin and eosin stain, demonstrating myxoma cells (asterisk) occluding the
lumen (arrows) of the artery (original
magnification, ⴛ100). C, elastin stain,
showing invasion and disruption (asterisk) of the elastic lamina (arrows) (original magnification, ⴛ400).
The natural history of myxomatous
aneurysms is not well characterized,
which further complicates treatment.
Both aneurysm enlargement with time
and spontaneous thrombosis and resolution have been reported (3, 18). Although both subarachnoid and intracerebral hemorrhage has been described
for patients with myxomatous aneurysms, a direct link between aneurysms

202

Jean et al.

and hemorrhage has been difficult to
prove (2, 7, 14). Bobo and Evans (2) described a patient with left thalamic hemorrhage, but myxomatous aneurysms
were observed only on the distal
branches of the right middle cerebral
artery. Reports of subarachnoid and intracerebral hemorrhage in patients with
atrial myxomas in the absence of cerebral aneurysms further obscure the
causal link (11, 13) and suggest that
bleeding in these cases may have resulted from hemorrhagic embolic vascular occlusion.
Interestingly, adjuvant treatment of
these aneurysms has been described in
only one report. Roeltgen et al. (18) used
doxorubicin to treat an enlarging right
middle cerebral artery myxomatous aneurysm in a 33-year-old female patient.
After a 6-month course of chemotherapy, the aneurysm exhibited no further
enlargement on follow-up angiograms.
Reluctance to use chemotherapy or radiotherapy has arisen from the uncertain efficacy of these modalities and the
unknown natural history of the disease.
In our case, options for adjuvant therapy are currently being considered.
For our patient, the transient ischemic
events were presumably related to local
vascular occlusion, as intraoperatively
observed in the cortical branch artery
associated with an aneurysm. Because
the patient did not experience recurrence of her cardiac tumor, the possibility of recurrent embolization from a central source was excluded. The presence
of the aneurysms does indicate, however, previous episodes of tumor embolization. We hypothesize that the
growth of these emboli with time led
not only to aneurysmal dilation of the
vessels but also to occlusion of smallercaliber vessels. Careful follow-up monitoring of these aneurysms is planned.

CONCLUSION
The development of multiple intracranial aneurysms attributable to oncotic embolization from atrial myxomas
is rare. Even more unusual is delayed
presentation with transient ischemic episodes years after surgical removal of
the tumor. Patients who have undergone successful resection of a left atrial
myxoma may be at risk for delayed ce-

rebral ischemia associated with aneurysm development, and this phenomenon must be considered for patients
with neurological symptoms even years
after myxoma removal.

ACKNOWLEDGMENTS
We thank Dr. Cornelius Lam for assistance with the manuscript. We did
not receive any financial or intellectual
backing for this report.
Received, November 2, 2000.
Accepted, December, 4, 2000.
Reprint requests: Eric S. Nussbaum, M.D.,
Department of Neurosurgery, University of
Minnesota, D429 Mayo Building, 520 Delaware Street SE, Minneapolis, MN 55455.
Email: nussb002@tc.umn.edu

REFERENCES
1. Bekavac I, Hanna JP, Wallace RC, Powers J,
Ratliff NB, Furlan AJ: Intra-arterial thrombolysis of embolic proximal middle cerebral artery
occlusion from presumed atrial myxoma. Neurology 49:618–620, 1997.
2. Bobo H, Evans OB: Intracranial aneurysms in a
child with recurrent atrial myxoma. Pediatr
Neurol 3:230–232, 1987.
3. Branch CL, Laster DW, Kelly DL: Left atrial
myxoma with cerebral emboli. Neurosurgery
16:675–680, 1985.
4. Browne WT, Wijdicks EFM, Parisi JE, Viggiano
RW: Fulminant brain necrosis from atrial myxoma showers. Stroke 24:1090–1092, 1993.
5. Burton C, Johnston J: Multiple cerebral aneurysms and cardiac myxoma. N Engl J Med 282:
35–36, 1970.
6. Castaigne P, Laplane D, Ricou P, Mallecourt J:
Multiple intracranial arterial aneurysms of mycotic appearance: Repeated vascular embolic accidents—Myxoma of the left atrium [in French].
Rev Neurol (Paris) 131:339–346, 1975.
7. Chen HJ, Liou CW, Chen L: Metastatic atrial
myxoma presenting as intracranial aneurysms
with hemorrhage: Case report. Surg Neurol 40:
61–64, 1993.
8. Damasio H, Seabra-Gomes R, da Silva JP,
Damasio AR, Antunes JL: Multiple cerebral aneurysms and cardiac myxoma. Arch Neurol 32:
269–270, 1975.
9. Desousa AL, Muller J, Campbell RL, Batnitzky
S, Rankin L: Atrial myxoma: A review of the
neurological complications, metastases, and recurrence. J Neurol Neurosurg Psychiatry 41:
1119–1124, 1978.
10. Diflo T, Cantelmo NL, Haudenschild CC,
Watkins MT: Atrial myxoma with remote metastasis: Case report and review of the literature. Surgery 111:352–356, 1992.
11. Knepper LE, Biller J, Adams HP, Bruno A: Neurologic manifestation of atrial myxoma: A 12year experience and review. Stroke 19:1435–
1440, 1988.

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12. Loeper J, Rouffy J, Loeper J, el-Hachimi A,
Hammou JC, Chomette G: Myxoma of the left
atrium resembling diffuse inflammatory
arteriopathy [in French]. Ann Med Interne
(Paris) 121:559–566, 1970.
13. Macaulay VM, Crawford PJ, McKeran RO:
Atrial myxoma presenting with cerebral haemorrhage. Postgrad Med J 61:331–332, 1985.
14. New PFJ, Price DL, Carter B: Cerebral angiography in cardiac myxoma. Radiology 96:335–
345, 1970.
15. Ng HK, Poon WS: Cardiac myxoma metastasizing to the brain. J Neurosurg 72:295–298, 1990.
16. Patte M, Rakofsky M, Telerman M, Struyven J,
Demeurisse G, Levi S: Left atrium myxoma discovered as the result of a cerebral angiography
[in French]. Acta Neurol Belg 73:252–263, 1973.
17. Price DL, Harris JL, New PFJ, Cantu RC: Cardiac
myxoma: A clinicopathologic and angiographic
study. Arch Neurol 23:558–567, 1970.
18. Roeltgen DP, Weimer GR, Patterson LF: Delayed neurologic complications of left atrial
myxoma. Neurology 31:8–13, 1981.
19. Samaratunga H, Searle J, Cominos D, Le Fevre
I: Cerebral metastasis of an atrial myxoma mimicking an epithelioid hemangioendothelioma.
Am J Surg Pathol 18:107–111, 1994.
20. Sandok BA, von Estorff I, Giuliani ER: Subsequent neurological events in patients with atrial
myxoma. Ann Neurol 8:305–307, 1980.
21. Steinmetz EF, Calanchini PR, Aguilar MJ: Left
atrial myxoma as a neurological problem: A
case report and review. Stroke 4:451–458, 1973.
22. Stoane L, Allen JH, Collins HA: Radiologic observation in cerebral embolization from left
atrial myxomas. Radiology 87:262–266, 1966.
23. Wada A, Kanda T, Hayashi R, Imai S, Suzuki T,
Murata K: Cardiac myxoma metastasized to the
brain: Potential role of endogenous interleukin-6.
Cardiology 83:208–211, 1993.

COMMENTS
This is a rare clinical presentation of
intracranial myxomatous aneurysms,
which presented as transient ischemic
attacks several years after apparently
successful treatment of the primary
atrial myxoma. The authors review the
approximately 15 cases with documented myxomatous aneurysms that
were previously reported in the literature. The findings from the biopsy of a
peripheral lesion in this case were consistent with previously published results. We also have encountered a case
of an atrial myxoma presenting with
transient ischemic attacks, and a similar
single peripheral aneurysm was excised. The diagnosis was established on
the basis of the histological examination
results, which led to cardiac evaluation
and excision of the primary myxoma.
In this case, the situation was quite
different and was indeed unusual. It is

Multiple Intracranial Aneurysms
not known whether the patient harbored clinically silent, intracranial, myxomatous aneurysms at the time of diagnosis and treatment of the atrial
myxoma. Such lesions might have gradually progressed, leading to occlusion of
a branch vessel and the presentation described. Another explanation might be
that microscopic myxomatous emboli
lodged in cerebral vessels, leading to
gradual aneurysmal degeneration with
time.
We agree with the authors’ approach,
with close expectant monitoring of these
lesions. Little is known regarding their
prospective natural history and associated prognosis. Only symptomatic and
more likely treated cases have been reported in the literature. Many others
may be undiagnosed, unrecognized,
and/or untreated. In contrast to bacterial mycotic aneurysms, the relationship
of these myxomatous aneurysms to
hemorrhage is not well established.
They are more likely associated with
ischemic complications or unrelated
brain hemorrhage. In some cases, they
have been observed to progress to parent vessel occlusion.
This case emphasizes the importance
of long-term monitoring of patients
with atrial myxomas, with a low index
of suspicion for thinking about and diagnosing these lesions. This report does
not address the question of whether
follow-up surveillance with magnetic
resonance angiography should be performed every few years for patients
with atrial myxomas.
Issam A. Awad
Denver, Colorado
The authors report the fascinating
case of a patient who presented with
transient ischemic attacks 5 years after
removal of an atrial myxoma. As the
authors document in their review of the
literature, it is extraordinarily rare for
such a patient to develop, years later,
multiple myxoma-related aneurysms
and neurological symptoms resulting

from them. This report should add a
level of complexity to the differential
diagnosis of patients who present with
transient ischemic attacks with a history
of atrial myxoma, even if treatment for
the latter condition occurred years earlier. This report also suggests that the
growth of tumor cells within the vessel
wall occurs very slowly and obviously
requires adjuvant therapy if the disease
is diffuse, as in this case.
H. Hunt Batjer
Chicago, Illinois
Jean et al. provide us with a fascinating case of a 32-year-old woman who
presented with transient ischemic attacks 5 years after seemingly successful
resection of her left atrial myxoma. Angiography demonstrated the presence of
multiple, peripherally located, fusiform
aneurysms, which proved to be myxomatous in origin after one such lesion
was excised and histologically examined. The authors suggest that late neurological complications resulting from
successfully treated left atrial myxomas
are quite rare. From their own literature
search, it can be concluded that the incidence is no greater than 3% among
patients who harbor these unusual tumors. Using the values provided by the
authors and knowing the size of my
own referral base, I calculate that, on
average, I should have encountered
only two such cases in my career to
date. Apparently I missed both of them.
A question that occurs to me as I read
this report is whether transthoracic
echocardiography is sufficiently sensitive to detect recurrence. Would transesophageal echocardiography or gated
magnetic
resonance
imaging
be
superior?
The real crux of the case, however, is
how to treat this individual. Antiplatelet
therapy has obviously proven to be successful in the short term. But will these
lesions progress? I think that everyone
would agree with the authors regarding
the need for close follow-up monitoring.

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203

The role of chemotherapy remains intriguing, although I certainly have no
answers in this regard. Like the authors,
I could find only one example in the
literature of adjuvant treatment for the
management of aneurysms associated
with an atrial myxoma. I did, however,
find another example of adjuvant treatment for the management of parenchymal metastases. Bernet et al. (1) described a 31-year-old male patient with
an atrial myxoma with metastases to
soft tissue, lung, and brain. The brain
metastases consisted of multiple parenchymal lesions, some measuring more
than several centimeters in size. The patient was treated with doxorubicin, ifosfamide, and external-beam radiation
(5000 cGy). After 10 years, the patient
was in clinically stable condition and
free of disease. Given the paucity of
data, however, I share the authors’ reservations regarding adjuvant treatment.
Although the authors did not elaborate on this point, I find the premise put
forth by Wada et al. (2) to be intriguing.
Those authors suggest that the endogenous production of interleukin-6 by
atrial myxomas may be related to their
potential invasiveness and ability to metastasize through vascular channels.
Further studies will be needed to determine whether serum levels of
interleukin-6 are in any way predictive
of future cerebral events. Given the rarity of this tumor type, however, I do not
expect to see such studies in the near
future.
Robert E. Breeze
Denver, Colorado

REFERENCES
1. Bernet F, Stulz PM, Carrel TP: Long-term remission after resection, chemotherapy and irradiation of a metastatic myxoma. Ann Thorac Surg
66:1791–1792, 1998.
2. Wada A, Kanda T, Hayashi R, Imai S, Suzuki T,
Murata K: Cardiac myxoma metastasized to the
brain: Potential role of endogenous interleukin-6.
Cardiology 83:208–211, 1993.