Neurological manifestations of atrial myxoma and stereotactic radiosurgery for metastatic aneurysms

Introduction

Atrial myxomas are the most common primary and benign cardiac tumours. They are believed to originate from multipotential mesenchymal cells (1, 2). Cardiac myxomas have been rarely reported to have various neurological manifestations including embolic stroke (3, 4), intracranial aneurysms and cerebral cavernous malformations (CCM) (5, 6).

Due to the rarity of the disease, optimal treatment has yet to be determined. It has been reported that myxomatous aneurysms can remain static over 15 years with observation (7). Surgical methods are limited by invasiveness especially for multiple recurring aneurysms. Chemotherapy alone has had equivocal results (8). Positive results have been reported with whole brain or focal irradiation followed by chemotherapy (9, 10).

We report the first case where stereotactic SRT was used alone to treat metastatic myxomatous aneurysms. SRT offers the advantages of being less invasive than endovascular or open surgery, avoids the systemic effects of chemotherapy, and limits toxicity to surrounding brain parenchyma compared to whole brain irradiation.

Case Presentation

A 57-year-old gentleman presented with subacute confusion and memory loss, brain computer tomography (CT) and magnetic resonance imaging (MRI) confirmed a bleeding right occipital vascular malformation. Craniotomy and excision of the lesion was done. Histology showed ectactic vascular spaces with small cords of spindly cells among a rich myxoid background staining calretinin positive, demonstrating a cavernoma with myxomatous invasion. He developed central retinal occlusion 6 months later. Investigation for sources of emboli led to discovery of a left atrial myxoma on echocardiogram. The cardiac myxoma was excised, with no recurrence on 2-year echocardiography follow up.

Two and a half years after initial presentation, interval brain CT angiogram (CTA) incidentally found multiple fusiform intracranial aneurysms at left anterior cerebral artery (ACA) A2 segment bifurcation, right middle cerebral artery (MCA) distal M2 segment, cortical branches at frontal and para-central regions, left posterior cerebral artery (PCA) P3 segment, and right occipital cortical branches, with progressive enlargement half-yearly.

Frameless stereotactic radiosurgery (SRT) was done for the high-risk metastatic intracranial aneurysms of >5mm. Subsequently, reassessment imaging was done at half yearly intervals. Aneurysms with significant enlargement one year after the first SRT were treated in a second SRT session. Treatment parameters are summarized at Table 1. The first SRT targeted the right MCA M2, left ACA A3 and left PCA P3 and was done at 5 Grays per fraction (Gys/fr), prescribed to the 80% isodose level (I.L.) for 5fr over 2 weeks.

Table 1.

Frameless SRT treatment parameters 2.5 years and 3.5 years after initial diagnosis

SRT session	Aneurysm Site	Target Volume	Treatment Volume	Coverage
First (2.5 years after diagnosis)	Right MCA M2	1.649cc	1.912cc	97.9%
	Left ACA A3	1.027cc	1.278cc	95.9%
	Left PCA P3	0.455cc	0.679cc	99.3%
Second (3.5 years after diagnosis)	Left ACA A3	1.323cc	1.992cc	97.6%
	Left MCA M3	0.486cc	0.765cc	99.5%

Follow up brain MR angiogram (MRA) 6 months post first SRT showed that among the irradiated lesions: the left PCA P3 aneurysm (previously 6.4mm) had resolved. Right MCA M2 and left ACA A3 had decreased in size (9.4 to 5.4mm and 8.1 to 6.3mm respectively)(see Figure 1). Out of the non-irradiated lesions, a left MCA M3 aneurysm increased from 5.0mm to 6.3mm, while other aneurysms remained similar. Cavernomas remained static.

Figure 1.

a) MRA showing Right MCA M2 aneurysm at diagnosis; b) MRA of Right MCA M2 aneurysm 6 months post 1^st SRT

Subsequent MRA 1-year post first SRT showed that the previously irradiated and responded left ACA A3 aneurysm had rebounded from 6.3mm to 9mm. A second SRT was done targeting the enlarging radiosurgery-naive left MCA aneurysm and rebounded left ACA aneurysm over 2 weeks at 5Gys/fr, 2-3 fr/week, prescribed to the 79% I.L (see Table 1).

Reassessment MRA was done at 6 months after second SRT, showing that the newly irradiated left MCA aneurysm regressed from 6.3mm to 4.9mm. However, repeat irradiation to the left ACA aneurysm did not yield significant size reduction. Among the lesions only treated in the first SRT session, the right MCA M2 aneurysm increased from 5.4-10.9mm, while the left PCA aneurysm remained resolved. Among the never-irradiated lesions, one of the two aneurysms at the right calcarine artery increased in size from 3.2mm to 4.3mm, other lesions remained similar.

Clinically, the patient had improved cognitive function with some residual memory loss 4 years after initial diagnosis.

Discussion

From initial diagnosis until prior to first SRT (over a course of 16 months), the aneurysms grew at a rate of 0.1-0.3mm per month. SRT for aneurysms >5mm produced positive short-term results of size reduction ranging from 1.8 to 6.4mm and resolution of one lesion. However, long-term results beyond 1 year were variable. Although there was no recurrence of the resolved aneurysm, 2 previously responded aneurysms rebounded in size. Repeat SRT also yielded less significant results than newly irradiated lesions. The smaller aneurysms that never underwent SRT either remained static or showed slight increase in size by 0.1mm/month, although it can be argued they may have an intrinsically lower risk of progression. Further observation and large-scale studies are needed to investigate the short and long term efficacy of frameless SRT as a treatment for myxomatous aneurysms.