The dynamic natural history of cerebral aneurysms from cardiac myxomas: A review of the natural history of myxomatous aneurysms

Abstract

We describe two contrasting patients with multiple cerebral aneurysms and a previous history of resected cardiac myxomas with no cardiac recurrence on follow-up echocardiography. Both patients presented with stroke- like symptoms; one with a left visual defect and the other with right hemiplegia. Magnetic resonance imaging of the brain of both patients showed the presence of multiple cerebral aneurysms that was later confirmed on conventional angiography. Both patients’ aneurysms were managed conservatively. Serial angiograms were performed during their follow-up, which spanned several years. One patient’s aneurysms remained static while the evolution of the other patient’s aneurysms displayed a dynamic quality with some increasing in size while others diminished. This is the first description in which some aneurysms progressed while others regressed simultaneously in the same patient. Aneurysms in patients with a history of cardiac myxoma can be active years after primary tumor resection and it is difficult to predict how they will develop. We reviewed the literature of all patients with multiple myxomatous aneurysms who were treated conservatively to better understand the natural history of this rare disease. Long-term follow-up of these patients may be necessary.

Introduction

In patients with cardiac myxomas, neurological symptoms can be the initial presentation in up to 50% of this population.¹ The most common cause of these symptoms is embolic infarct but direct invasion of the vessel wall by the tumor with subsequent arterial aneurysms is sometimes seen. Medical management of this rare disease is controversial owing to the lack of long-term follow-up and the unclear natural history of patients with myxomatous aneurysms. We present two patients who had resected atrial myxomas with multiple cerebral aneurysms confirmed by angiography and the long-term evolution of these untreated lesions. We also reviewed the literature to determine the natural history of such patients with multiple myxomatous aneurysms who were managed conservatively.

Case presentations

A 61-year-old man with a past history of minor strokes more than 20 years ago and residual expressive dysphasia presented with an acute onset of rotational vertigo and left visual field deficit. Magnetic resonance imaging (MRI) revealed a flow defect in the basilar artery and several posterior fossa aneurysms. There were no hyperintensities seen on the diffusion-weighted imaging (DWI) sequences. Diagnostic angiography showed a fenestration of the basilar artery as well as better delineated the multiple fusiform aneurysms (Figure 1). A left atrial myxoma was discovered during a routine two-dimensional echocardiography and resected (Figure 2(a)). A multidisciplinary team decided on a conservative approach toward the multiple aneurysms based on the absence of any sign of hemorrhage, and the not-insignificant treatment risk of coiling the aneurysms. The patient recovered well and remained asymptomatic; at a follow-up angiogram 18 months later, the aneurysms were unchanged. The patient is scheduled for a repeat computed tomographic angiography in three years’ time.

Figure 1.

(a) and (b) Left vertebral artery digital subtraction angiography anteroposterior and lateral views showing a fusiform aneurysm in the left posteroinferior cerebellar artery. (c) Right internal carotid artery digital subtraction angiography lateral view showing two aneurysms in the M2 segment of the right middle cerebral artery.

Figure 2.

(a) Histology of the resected tumor showing loosely packed cords of stellate and plump cells with eosinophilic cytoplasm containing vacuoles within a bland myxoid stroma. The surface of the tumor was generally villous. (b) Similar histology showing loosely arranged cords of stellate and plump cells with eosinophilic cytoplasm and vacuoles, with a varyingly smooth or villous surface. The central part of the lesion was fibrotic containing myxoma cells and hemosiderin-containing macrophages indicating an earlier bleeding.

The second patient is a 19-year-old woman who presented to the emergency department with right-sided hemiparesis lasting for one hour. The patient had two previous admissions for loss of consciousness and was initially diagnosed with Todd’s paresis secondary to epilepsy. An MRI did not show any acute infarct; however, it revealed multiple aneurysms in different arterial territories. Conventional angiography confirmed the presence of multiple fusiform cerebral aneurysms affecting several distal branches of both middle cerebral arteries (MCAs).

A cardiac ultrasound was performed that disclosed a left atrial myxoma and the tumor was resected surgically (Figure 2(b)). After discussion with a multidisciplinary team, the patient’s aneurysms were managed conservatively, with close follow-up via yearly MRI and conventional angiography. Over the next five years, several aneurysms enlarged while others regressed in size (Figure 3). The largest aneurysm increased significantly in size between examinations and she developed an alternate transdural blood supply from the middle meningeal artery, likely secondary to focal ischemia distal to this aneurysm (Figure 4). This patient is currently asymptomatic and is planned for follow-up angiography with possible endovascular treatment if the aneurysms continue to increase in size.

Figure 3.

Lateral views of serial digital subtraction angiographies in (a) 2011, (b) 2013, (c) 2014 and (d) 2016, showing enlargement and regression in different aneurysms simultaneously in the left internal carotid artery territory.

Figure 4.

Digital subtraction lateral views after contrast injection of the left external carotid artery showing transdiploic blood supply to the left parietal lobe that developed between 2011 and 2014.

In an effort to better delineate the natural history of multiple myxomatous aneurysms, we performed a literature review and included any patients who had multiple myxomatous aneurysms that were treated conservatively and had a period of follow-up described. Patients who had surgery or endovascular treatment that would interfere with the natural history of the disease were excluded from this review. Of 30 patients, including the two patients from this paper, 21 (70%) patients were female with a mean age of 37.4 ± 15.4 years and with a mean follow-up of 41.5 ± 67.8 months. Nineteen (63.3%) patients had stroke-like neurological symptoms on presentation while two (6.7%) patients died and six (20%) patients had recurrent ischemic events during follow-up. One patient died from a large corpus striatum bleed that herniated and the other died from status epilepticus. In this cohort, 17 patients had repeat imaging during follow-up, three patients (17.6%) had enlarging aneurysms and three (17.6%) showed aneurysms reducing in size. One of our patients showed both an increase and decrease in the size of the aneurysms. The rest of the 10 (58.8%) patients had aneurysms that were stable on serial imaging.

Discussion

This is the first record of patients with aneurysms arising from cardiac myxomas, which suggests that they can have a variable natural history in the same patient, that is, the possibility of resolution or progression in size over time in different aneurysms simultaneously in the same patient. We have also compared our patients with the existing literature. Other case series have tended to include patients with aneurysms that were treated whereas we included patients with only conservative treatment in our literature review to have a better understanding of the natural history.

Cardiac myxomas are the most common cardiac tumors and originate from the mesenchymal cells of the septal endocardium.^2,3 Although they are benign tumors, they can embolize and seed the brain, causing ischemic events or, less commonly, aneurysms. Evidence of embolism can be seen up to 50% of patients with left atrial myxoma and half of these have cerebral involvement.¹ The underlying pathological processes for intracranial aneurysms in conjunction with cardiac myxomas is not well established. Myxomatous emboli can invade through the endothelium of the vessel wall or via the vasa vasorum, destroying the architecture of the vessel, scaring the endothelium and subsequently altering flow dynamics, which lead to aneurysm formation.⁴ Myxomatous emboli have also been postulated to result in vascular occlusion of the vasa vasorum with an inflammatory response. Finally, tumor cells can proliferate and penetrate the wall both leading to scarring of the vessel’s wall and pseudoaneurysm formation.⁵

Myxomas typically present with symptoms of reduced cardiac output, non-specific symptoms such as fever, weight loss and myalgia. Neurologic complications resulting from cardiac myxoma are seen in up to 35% of patients with myxomas.⁶ This is largely due to an embolic phenomenon causing ischemic stroke although mass effect from aneurysms and tumor seeding has been reported.⁷ In our series, both patients presented with neurological symptoms, presumably caused by myxomatous tumor emboli, although neither had acute DWI changes on MRI. After treatment and resection of the myxoma, both patients showed clinical improvement. This clinical resolution did not correspond to the evolution of the aneurysms.

The angiographic features of myxomatous aneurysms share some similarities with human immunodeficiency virus (HIV)- or other immunodeficiency-associated aneurysms and septic emboli causing aneuryms.^8,9 Similar to HIV-related aneurysms, they tend to occur in small- to medium-sized vessels and may lead to ischemic and/or hemorrhagic sequelae. They tend to be multiple, fusiform in shape and are normally found in distal locations as was seen in both patients. In the face of an unknown etiology of stroke, it is advisable to perform a transesophageal cardiac ultrasound to exclude infective endocarditis or cardiac myxoma, even with a normal cardiac auscultation and transthoracic echocardiography.¹⁰ Histological characteristics of the resected myxomas can provide an estimate of the risk for embolization, with irregular pedunculated myxomas being more likely to embolize than villous or sessile myxomas.¹¹ The predilection for embolization of cardiac myxomas cannot be completely determined by histology. This was shown by the fact that both of our patients with villous cardiac myxomas still developed multiple myxomatous aneurysms from emboli. The incidence of embolization has also been reported to be unrelated to the size of the cardiac myxoma.¹² There are at present no guidelines for screening for intracranial aneurysms after a cardiac myxoma has been diagnosed, although the current literature does suggest that patients with embolic complications have higher rates of aneurysm formation. One study found almost 30% of patients with embolic complications developed myxomatous aneurysms compared to only 3% in patients without embolic complications.¹³ Finally, high-resolution MRI of the vessel wall with black-blood sequences to study walls of the aneurysm and the presence of inflammation can help in planning for treatment. This is especially so in cases of multiple aneurysms to determine which one is the culprit for a bleed or at a higher risk of bleeding.¹⁴

The recurrence rate of cardiac myxomas in the heart is well documented with 1%∼3% recurring after resection.¹⁵ Therefore, long-term follow-up with echocardiography for all patients with myxomas is recommended. Conversely, there is little information regarding the natural history of myxoma-associated aneurysms in the cerebral vasculature;¹⁶ it is known that they can appear years after removal of the cardiac tumor and this can occur even without recurrence of the cardiac tumor.¹⁷ Our case series shows that the evolution of these aneurysms is variable with the possibility of progression or regression in size (Figure 4). The optimal follow-up period or treatment of these aneurysms has not been established and will depend largely on the symptoms, size, shape and location of the aneurysms from which we can approximate bleeding risk. From our literature review, it seems that there is a relatively high risk of recurrent ischemic events (Table 1). Our findings will also need to be validated in a larger case series.

Table 1.

List of cases with multiple myxomatous aneurysms treated conservatively.

Authors	Year	Age	Sex	Neurological presenting symptoms	Follow-up (months)	Outcome	Follow-up imaging
Zheng et al.18	2015	39	F	Headache and giddiness	14	Well	No
Stoane et al.19	1966	29	M	Nil, incidental finding	2	Well	Yes, DSA, aneurysms enlarged
Price et al.20	1970	21	F	Headache, confusion, diplopia	27	Ischemic stroke and death	Yes, DSA, aneurysms enlarged
Damásio et al.21	1975	43	F	Recurrent psychiatric symptoms, diplopia, gait disturbance	12	Well	No
Branch et al.22	1985	53	F	Hemiplegia	18	Well	Yes, DSA, aneurysms resolving
Hung et al.23	1992	10	F	Hemiplegia	8	Well	Yes, DSA, aneurysms stable
Suzuki et al.24	1994	34	F	Not available	5	Well	Yes, DSA, aneurysms enlarged
Mattle et al.25	1995	49	M	Progressive dementia	60	Recurrent TIA and progressive dementia	No
Oguz et al.26	2001	40	M	Numbness in right arm, blurred vision	12	Well	Yes, MRI, aneurysms stable
Stock27	2004	22	F	Acromegaly	132	Well	Yes, DSA, aneurysms resolving
Ashalatha et al.4	2005	54	M	Aphasia and hemiplegia from left MCA stroke	6	Multiple ICHs	No
Josephson and Johnston28	2005	33	F	Multiple embolic strokes	96	Well	Yes, MRI, aneurysms stable
Herbst et al.29	2005	31	M	Giddiness from cerebellar strokes	24	Well	No
Sabolek et al.30	2005	43	F	Headache, nausea, reduced consciousness	15	Progressively decreased intellect	Yes, DSA, aneurysms resolved
Chen et al.31	2005	19	F	Seizures, multiple infarcts	12	Well	No
Namura et al.32	2007	45	M	Right-hand sensory loss and gait disturbance from infarcts	120	Recurrent stroke	Yes, DSA, aneurysms stable
Kvitting et al.33	2008	55	F	Left hemiplegia	6	Recurrent strokes	No
Li et al.34	2008	27	F	Vertigo, dysarthria and right hemiplegia with multiple infarcts	24	Well	No
Ryou et al.35	2008	27	F	Giddy, headache, blurred vision	132	Well	Yes, DSA, aneurysms stable
Shinn et al.36	2009	48	F	Syncope, seizure	3	Death	No
Koo et al.37	2009	64	F	Dysarthria, gait disturbance from multiple infarcts	6	Well	Yes, CTA, aneurysms stable
Tamulevičiūtė et al.38	2011	29	F	Left-sided weakness from stroke	336	Recurrent TIA	Yes, DSA, aneurysms stable
Radoi et al.5	2012	45	M	Headache, giddy, left-sided weakness, seizures	12	Recurrent seizure	No
Lee et al.39	2012	55	F	Nil, incidental finding	47	Well	No
George et al.40	2012	45	F	Headache, TIA	6	Well	Yes, DSA, aneurysms stable
Kim et al.41	2012	58	F	Nil, old strokes	12	Well	No
Takenouchi et al.42	2014	14	F	Transient left-sided weakness and aphasia	7	Well	No
Gupta and Agrawal43	2015	11	M	Hemiplegia and facial weakness from stroke	12	Recurrent stroke	Yes, DSA, aneurysms stable
Current study Patient 1	2018	61	M	Vertigo and visual field defect	18	Well	Yes, DSA, aneurysms stable
Current study Patient 2	2018	19	F	Right-sided weakness	60	Well	Yes, DSA, aneurysms both enlarged and regressed

CTA: computed tomographic angiography; DSA: digital subtraction angiography; F: female; M: male; ICH: intracerebral hemorrhage; MCA: middle cerebral artery; MRI: magnetic resonance imaging; TIA: transient ischemic attack.

The treatment options are between open surgery, endovascular approaches or conservative treatment. Patients with acute intracranial bleeding are typically considered urgent surgical candidates and even more so if a craniectomy is necessary. However, the fusiform shape of these aneurysms means that the preservation of the responsible vessel can be difficult and sacrifice of the feeding artery may be required. There are several endovascular options available; coiling alone with embolization of the vessel may not be sufficient because of the aforementioned fusiform shape. Stenting the feeding artery with a flow diverter could be a reasonable option although evidence in the literature is lacking. Finally, spontaneous regression of these aneurysms after excision of the cardiac tumor has been frequently reported.^27,28,30 These aneurysms can be stable over many years and conservative treatment with long-term close MRI or angiography follow-up to evaluate the progression or resolution of these aneurysms may be a suitable strategy, especially if the risks of surgical or endovascular methods are high.³⁸ Another method that is still controversial is to treat enlarging aneurysms, which are not good candidates for surgical or endovascular treatment, with chemotherapeutics to stabilize the lesions.⁴⁴

Conclusion

Myxomatous aneurysms should be suspected in patients with history of cardiac myxoma and neurological symptoms. These aneurysms appear to have a variable progression, and long-term follow-up in the form of intracranial vascular imaging may be prudent, pending a larger series to validate our findings.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.