Case Reports
Case 1
A 14-year-old girl presented with sudden-onset aphasia and right-sided weakness. She
had a history of generalized tonic-clonic epileptic seizures from the age of 11.
A computed tomography (CT) scan showed hypodensity in the left MCA territory. On echocardiography,
a 39 × 17 mm tumor in the left atrium was identified, suggesting atrial myxoma. Surgical
excision of the myxoma was performed in another hospital. The neurological condition
of the patient improved, but a learning disability ensued, as well as preserved oral
comprehension with slower verbal information processing and oral expression characterized
by hesitation and moderate anomia. Speech therapy and persistence of school activities
enabled continued improvement.
On digital cerebral angiography performed after the cardiac surgery, multiple aneurysmatic
lesions in the anterior and posterior circulations were identified. The most evident
lesions were in the bifurcation of the left MCA, in the A2 and A3 segments of the
ACA, and in the right PICA ([Fig. 1]). We proposed endovascular treatment, preceded by a test occlusion and occlusion,
if possible, but the parents did not accept the risks of a cerebellar infarction even
after explanation of the hemorrhagic risk and its consequences. Therefore, a conservative
treatment was chosen.
Fig. 1 Diagnostic cerebral angiogram showing a right posterior inferior cerebellar artery
aneurysm. Notice the fragility spots represented by lobulation and the two small aneurysms
in the superior branch.
We performed a control MRI angiography, that showed the aforementioned lesions with
no significant change compared with the previous test, and an additional lesion located
inside a sulcus in the posterior temporal region. Digital cerebral angiography showed
stable lesions, and there was no increase in size or number of lesions in a 2-year
outpatient follow-up.
Case 2
A 47-year-old woman was admitted to our hospital with generalized tonic-clonic seizures.
A CT scan showed two areas of hemorrhagic stroke on the right parietal lobe, on the
posterior right MCA territory. The patient was awake and oriented, with a slight left
hemiparesis on physical examination. She had a history of a cardiac myxoma surgery
3 months before, without surgical or postsurgical complications.
Magnetic resonance imaging depicted multiple foci of sulcal and intraparenchymal lesions,
one of which showed evidence of hemorrhage (a small 1 cm parietal hematoma), suggesting
multiple intracranial cavernomas. The clinical information provided to the radiology
did not mention her cardiac history.
Clinical treatment of the low volume hematoma was chosen, with general clinical improvement,
cessation of seizures, and residual occasional headaches.
After 2 months, the headaches worsened, and a follow-up MRI made in another institution
([Fig. 2]) depicted several foci seen before, but which now showed an increase in volume in
2 lesions, with perilesional hemorrhage in 1 of them. Gadolinium-enhanced T1 images
showed continuity of the lesions with distal blood vessels, suggesting fusiform aneurysms,
the larger one located in the right precentral gyrus, with vasogenic edema in the
surrounding parenchyma. Minute hyposignal foci in SWI-weighted imaging in the cerebellum,
brainstem, and cerebral hemispheres suggested microhemorrhages.
Fig. 2 Follow up magnetic resonance imaging studies obtained 2 months after initial presentation.
Axial susceptibility weighted images (SWI) (a, b) and 3D axial T1 weighted images (c, d) at the same anatomic level for comparison. Note the round blooming artifact in SWI
in the right parietal region, consistent with hemorrhage, as well as small amounts
of linear blood in the sulci diffusely. There is contrast enhancement in the right
parietal lesion, corresponding to the larger aneurysm seen on digital subtraction
angiography.
Digital subtraction 3D angiography (3D DSA) showed 7 fusiform aneurysms in the territory
of the right MCA ([Fig. 3]), 5 in the left MCA territory and four aneurysms in the distal PCA territory (2
on the left and 2 on the right side). Most of these lesions remained opacified until
the late venous phase.
Fig. 3 3D digital subtraction angiography showing multiple fusiform aneurysms on the right
middle cerebral artery distal branches.
A diagnostic echocardiography showed no remaining atrial myxomas. Based on the symptoms
and on the findings of increased lesion volume, a multidisciplinary team comprised
of therapeutical neuroradiologists, oncologists and radiation therapists chose radiation
therapy as the best course of action. Two lesions were irradiated, 1 in the frontal
and another in the parietal region, measuring 1.6 and 1.3 cm, respectively. The treatment
was performed with stereotactic ablative radiotherapy (SABR, also known as radiosurgery),
with a single dose of 1200 cGy, in a linear accelerator with Agility multileaf collimators
(Elekta Corporation, Stockholm, Sweden). We decided to only treat these lesions due
to the evidence of volumetric progression when compared with previous diagnostic images,
which was lacking in the other lesions.
Follow-up brain MRI and cerebral angiogram performed after 2 years of follow-up, in
January 2021, showed stability of both treated and untreated lesions, with no evidence
of disease progression or new lesions. The patient was clinically stable, without
new seizures. Annual MRI and MRA follow-up was decided as the management strategy
for the patient, with digital subtraction angiography as a possible choice in case
the noninvasive images showed progression of the lesions.
Discussion
Clinical Presentation and Pathogenesis
Cardiac myxomas are benign lesions originated from subendocardial mesenchymal cells
commonly located in the left atrium, at or near the interatrial septum. There is a
female-to-male ratio of 2:1 and they are more frequent between the 3rd and 6th decades of life, although children and elderly individuals may be affected.[4]
They can be solid or soft (papillary subtype) and, in these cases, they may be pedunculated,
and intermittently stop the flow across the mitral valve, leading to syncope. Most
of the times the lesions are benign but may recur after initial surgical treatment
if incompletely resected. Malignant transformation has been reported. Recurrence has
been reported in the familial myxoma syndrome.[5]
The clinical presentation may range from asymptomatic to sudden death. Cardiac symptoms
such as dyspnea, syncope, and cardiac murmur may occur when the tumor is solid, and/or
embolization when the papillary subtype is involved.[6]
The triad of symptoms of cardiac myxoma include:[7]
-
Inflammatory syndrome, with symptoms such as myalgia, arthralgia, fever, with elevated
erythrocyte sedimentation rate and C-reactive protein (CRP) levels.
-
Embolic presentation, most commonly to the brain or systemic circulation, as tumors
are often left-sided in the heart
-
Valvular heart obstruction, leading to pulmonary edema with dyspnea and, less commonly,
right heart failure.
Myxomas produce growth factors such as vascular endothelial growth factor (VEGF),
resulting in angiogenesis, which may explain why they are more invasive to blood vessels
than other tumors. They proliferate under the intimal layer of the artery, and may
progress to invade the whole vessel wall, leading to rupture.
Overproduction of interleukin-6 (IL-6) could be responsible for the inflammatory presentation,
recurrence, and distal embolization of cardiac myxomas.[8] High levels of IL-6 leads to upregulation of matrix metalloproteinases, consequently
with degradation of the arterial wall collagen and aneurysmal genesis.[9]
Interleukin-6 may be a more sensitive biomarker than CRP for evaluation of the inflammatory
status of patients with cardiac myxoma. The normalization of circulating IL-6 levels
can be of value in the follow-up of patients after cardiac tumor resection.[10]
About 30 and 40% of patients will suffer tumor embolism in the lungs, in the brain
or in the systemic circulation. Factors associated with an increased risk of embolism
include:
-
Echocardiographic irregular tumor surface (polypoid tumors) embolize much more frequently
than round tumors (58 versus 0%).[11]
-
Atrial fibrillation, larger tumor size, and an increased left atrial diameter.[12]
The tumor location (left or right atrium) and/or presence of a persistent foramen
ovale will determine the site of embolism.[13]
Neurologic symptoms will occur in ∼ 30% of patients with an atrial myxoma, and in
almost half of these, the neurologic manifestation will precede the cardiac symptoms.[14]
Three distinct neurological presentations have been described:[15]
-
Embolic ischemic stroke.
-
Intracranial aneurysms.
-
Intracranial metastases (the most uncommon presentation).
The aneurysm cases we present here are of two women, both with multiple lesions. We
will summarize the characteristics and treatment options of these aneurysmal lesions.
The initial presentation of both patients was tonic-clonic seizures. Patient 1 did
not bleed, but patient 2 had a hemorrhagic stroke due to a ruptured distal fusiform
aneurysm. Only after that, the cardiac myxoma was found.
Also, in both patients, the main patterns of aneurysm distribution were multiplicity
and always had a distal location. The topography was most frequently in the MCA and
PICA territories, but also in the PCA. No aneurysm was found in the ACA territory.
The shape of the lesions was always fusiform. In patient 2, there were significant
irregularities in the PICA aneurysms ([Fig. 1]), which indicated test occlusion and occlusion, if possible, but the parents did
not accept the risks.
In patient 2, some aneurysms coexisted with hypodense areas on MRI (old hemorrhagic
sites), which presented as gyral pattern of marked signal loss on T2WI and SWI. Of
note, homogenous enhancement surrounding the aneurysms was detected on contrast-enhanced
MRI.
The neurologic presentation may occur before, at the time, months or even years[16] after the clinical manifestation or diagnosis of the primary tumor. In our cases,
the presentation consisted of seizures and only after the imaging features of the
brain (MRI angiography) it was thought to be related to an embolic event.
The histopathological type of both tumors was papillary myxoma. The mobility, but
not the size of the myxoma appears to be related to the embolic potential,[3] and the friable and gelatinous papillary myxomas embolize more often than solid
lesions.
All patients had multiple fusiform aneurysms in distal locations. There are three
hypotheses for the genesis of these lesions:[3]
-
Embolic fragments of the tumor leading initially to vascular occlusion and destruction
of the arterial wall and/or myxoma cells would proliferate without apoptosis, leading
to occlusion.
-
Hematogenous dissemination of lesions with cerebral vasa vasorum invasion, leading
to destruction of the arterial wall, particularly of the internal elastic lamina,
resulting in aneurysm formation.
-
A combination of the two mechanisms above: myxomatous tumor emboli leading to invasion
of the vasa vasorum, apoptosis and destruction of the vessel wall, widening of the
arterial lumen, and fusiform aneurysm formation.[17]
Differential Diagnosis
Echocardiography should be performed in all patients with suspected embolic events,
especially when cerebral infarcts or hemorrhages in multiple arterial territories
are identified. On noncontrast CT, the aneurysms are spontaneously hyperdense, due
to accumulation of myxoid matrix or to calcification in their walls. Also, there are
abnormal findings surrounding the myxoid aneurysms, like signal loss on T2-weighted
images, enhancement in contrast-enhanced T1 images and on CT, due to myxoid accumulations,
angiogenesis, or granulation tissue. These perilesional changes may contribute to
differentiate these aneurysms from other lesions, as described below:
Cavernoma: Cavernomas are not seen on angiography, but on MRI images, both may appear
as large-volume lesions surrounded by an irregular hemosiderin ring; different degrees
of perilesional edema can exist simultaneously and both show a blooming effect on
gradient-echo and susceptibility images, but only the myxoid aneurysms are clearly
identifiable on T1-weighted images.[4]
Mycotic aneurysms: angiographic findings of myxoid aneurysms are not different from
the most common mycotic (septic) aneurysms: multiple lesions that are fusiform in
shape and peripheral in topography. The finding of persistent hyperdensity in noncontrast
enhanced CT scan may suggest a myxoid origin: histopathological studies showed accumulation
of myxoid, hemosiderin, and iron from recurrent chronic hemorrhages, but not calcification.[18] Septic aneurysms are more prone to rupture, resulting in subarachnoid hemorrhage
or hematoma around the lesions.[2]
Other neoplastic intracranial aneurysms: choriocarcinoma and lung carcinoma metastases
generally are single lesions and may lead more frequently to intracranial hemorrhage
(100% in choriocarcinoma and 84% in lung carcinoma). Instead, myxoid aneurysms are
almost always multiple and the rate of intracranial hemorrhage is much lower (19.6%).[19]
Treatment Options for Myxomatous Intracranial Aneurysms
Early cardiac surgery with extreme caution not to allow the myxoma to embolize intraoperatively
is the best treatment to reduce the possibility of embolic complications or sudden
death, as well as for optimally preventing these serious lesions from reaching the
central nervous system.
After cardiac surgery, these patients need frequent neurological examination, as well
as echocardiography, brain MRI and MRA, and must be made aware of the need to seek
medical attention should any neurological symptom arise.
In a study of 58 patients with myxomatous intracranial aneurysms, the incidence of
rupture was 19.6% in 11 years.[19] A meta-analysis[20] of 37 patients with multiple myxomatous intracranial aneurysms showed 76% of stability
or regression of these lesions, enlargement of 21%, and mortality of 3.4%.
The management of intracranial myxomatous aneurysms is controversial. The resection
of the atrial lesion does not avoid the continuous growth of these lesions in the
central nervous system, if they are already present, with risk of hemorrhage.
There is no definitive guideline available in the current literature, so decisions
should be made case by case. Surgery, embolization, and surgery with adjuvant chemotherapy
have been proposed, with or without adjuvant low-dose radiation therapy.[21]
Conservative Treatment
Given the poor understanding of the natural history of these lesions, a conservative
management is mandatory in most asymptomatic patients with stable and nonhemorrhagic
lesions.[22]
Follow-up imaging may show stability or even regression of some lesions after cardiac
tumor removal.[20]
[23] In a series of 37 cases, 78.4% were managed conservatively and 75,9% with stable
or even regression, with a mortality of 3.4%. In the present study, 20.7% of the cases
demonstrated aneurysmal enlargement, without symptoms or bleeding.[19]
Noninvasive Methods
The pathogenesis and further growth of myxomatous aneurysms is linked to the proliferation
of neoplastic cells inside the arterial wall. Therefore, radiation and chemotherapy
have been used in selected cases to try to halt their growth.[24] There are limited reports of such treatments, so their efficacy remains unproven.
Radiation Therapy
The effects of radiation in metastatic myxomas are extrapolated from the response
seen in the setting of tumors and especially of brain arteriovenous malformations,[25] including endothelial damage, arterial wall smooth muscle proliferation, and intraluminal
platelet aggregation with microthrombosis, resulting in vessel obliteration. The parent
vessel occlusion with radiation has a slow course, allowing for the opening of collateral
circulation, avoiding ischemic events. Furthermore, given the differential response
to radiation of neoplastic cells, it could interrupt the proliferation of myxomatous
cells and, consequently, aneurysmal enlargement.[24]
There are many reports of successful treatment of metastatic myxoma,[21] but for the treatment of myxomatous intracranial aneurysms, we have found only two
literature reports of radiation therapy for multiple lesions located in eloquent areas,
in which parent artery surgical or endovascular ligation would be highly deleterious.
One single case report used 45 Gy low-dose fractionated radiation in multiple myxomatous
aneurysms, with occlusion of the lesions and parent vessels on control angiograms.[17] The other report treated with 14 Gy, obtaining the same effect (aneurysmal and parent
vessel occlusion), claiming to minimize the risks of adverse effects of radiation.[24]
The main issue with monotherapy with radiation is similar to its use in treating hemorrhagic
brain arteriovenous malformations[26]: in hemorrhagic myxomatous aneurysms, the latency period until radiation promotes
protection may put the patient at risk of new bleeding episodes.
Chemotherapy
In cases of evolving symptomatic masses, chemotherapy might be considered. Etoposide
and carboplatin have been used[27] in severe cases, but their efficacy is poor, and most medical centers are cautious
about their use due to a lack of clinical experience and of high-quality studies.
Invasive Methods
As most lesions occur in distal branches, surgical excision remains the option of
choice in selected cases. In determining the best treatment option, lesion topography,
morphology, and clinical and aneurysm size evolution are important factors to help
decide between surgical or endovascular approach. The same patient may even need both
methods of treatment for multiple lesions.[28]
Surgical Treatment
In cases in which there is significant increase in lesion size, craniotomy may be
indicated for decompression. In the subdural space, thrombi may be seen on the brain
surface, as well as mucinous masses and yellow staining. It is often not possible
to remove the aneurysms due to the eloquent territory irrigated, and the low risk
of bleeding. Thus, postoperative MRI or DSA may show persistence of the aneurysms,
with amelioration of the mass effect.
In those cases in which the lesion is close to the cortical surface, and with small
parent vessels, the use of a neuronavigational system to guide craniotomy may be chosen,
followed by exploration of the sulcus harboring the lesion. After identification of
the dilated fusiform artery, coagulation and/or clipping of the afferent and efferent
artery is performed, allowing for safe removal of the aneurysm. Bypass should be considered
for those lesions in eloquent areas, since clip reconstruction is impossible due to
the friability of the aneurysms.[16]
[29]
Endovascular Treatment
For acute vascular occlusion, intravenous thrombolysis has been attempted in emergency
stroke care scenarios, without the knowledge of a cardiac myxoma as the underlying
condition.[30] From a practical standpoint, this can be effective in restoring the blood flow and
improve the prognosis in patients with cerebral embolism due to a cardiac myxoma,
but the possibility of a hemorrhagic complication in the setting of a coexisting myxoid
aneurysm must be remembered.
Consequently, unstable (growing) and symptomatic intracranial myxoid aneurysms, although
with a low risk of rupture, may need to be occluded. As a fusiform lesion, they must
be occluded sacrificing the artery closely proximal and distally to them (the so-called
“deconstructive approach”) with a liquid embolic. This may pose a very difficult decision,
as neurological deficits may appear after ligation.
One advantage of the endovascular method is the possibility of performing balloon
test occlusion before this decision, with the patient awake, in an attempt to predict
the clinical consequence of sacrificing the vessel. Rarely, some deficits may appear
lately, only after increased metabolic demands such as that due to physical exercise.
After aneurysm and vessel occlusion, although the hemorrhagic risk is eliminated,
the lesion itself or its surroundings may continue to grow as a tumor. This would
be the case to treat with chemotherapy or radiotherapy soon, although in most reported
cases these embolized lesions remained stable on follow-up after embolization,[20] possibly because embolization devascularizes the region, causing decreased blood
flow to neoplastic cells and lowering the risk of tumoral growth.
