Cerebral aneurysm associated with cardiac myxoma : Case report

Left atrial myxomas are a rare but well known cause of cerebrovascular accidents in young people. Cerebral embolism is the most common cause of cerebral ischemic stroke. Th e intracranial aneurysm is rarely associated with myxoma. We report the case of a patient who had an operation of PICA aneurysm due to subarachnoid hemorrhage ten months before the discovery of the large left atrial myxoma. Fortunately, the untimely diagnosis of the myxoma did not have other consequences. In order to prevent possible complications of we should keep in mind that these two apparently diff erent entities could be associated. ©  Association of Basic Medical Sciences of FBIH. All rights reserved


Introduction
Atrial myxomas represent approximately  of all cardiac tumors.About  of them are located in the left atrium [].Th ey are often a source of systemic embolism (central and peripheral).To be more precise, the embolization of tumor particles or thrombotic material mixed with tumor cells occurs in - of patients with myxoma [].There were reports of the embolisms of cerebral vessels, coronary and renal arteries, spleen, mesenteric arteries, and lower limbs arteries [].In at least half of the cases cerebral arteries were affected, leading to the embolic ischemic strokes [,].In addition to these neurological manifestations of myxomas, it is extremely rare to find myxoma associated with intracranial aneurysms or parenchymal brain metastases [,].We report the case of a patient who had the operation of a. posterior inferior cerebelli (PICA) aneurysm due to subarachnoid hemorrhage ten months before the discovery of the large left atrial myxoma.

Case report
A -year-old woman was admitted to our hospit a l w i t h d y s p n e a a t r e s t a n d p a l p i t a t i o n .Ten months earlier the patient was hospitalized at the Clinic for neurosurgery due to subarachnoid hemor-rhage.The -vessels cerebral angiography immediately was done.It revealed small saccular aneurysm diameter  mm and diameter of neck  mm arising from the origin of left posterior inferior cerebelli artery directed backwards, upwards and lateral (Figure ).The patient was operated and clipping of the saccular aneurysm neck was done.A month after the operation, fatigue, myalgia, and palpitations appeared and objective examination for the fi rst time revealed a heart murmur.The patient was indicated for echocardiographic examination which she refused.In the meantime, she lost  kg of body weight.A month before hospitalization dyspnea on minimal exertion, provoked by changed body position, appeared.A few days before admission to hospital she had dyspnea even during conversation.Th ere were no data about conventional cardiovascular risk factors, familial medical history of stroke or taking contraceptives.On examination patient was pale, hypotensive with normal body temperature.Her arterial pressure in the sitting position was / mmHg and / mmHg in standing position, her heart rate was /min.Th ere was no jugular venous distension.Th e lungs were clear, auscultation revealed regular heart action, accented and split fi rst sound with diastolic murmor on the apex.Th e liver and spleen were not palpated under the costal margin.Peripheral edema was not noticed.Mucocutaneous lesions or any element of excessive neuro-endocrine activity were not manifested in our patient.Routine blood tests were normal including the erythrocyte sedimentation rate ( mm/for the first hour), the level of CRP ( mg/l) and globulin level ( g/l).An electrocardiogram registered sinus tachycardia.Chest roentgenogram was normal.Two-dimesional transtho-racic echocardiographic (TTE) examination revealed a large polypoid tumor mass with irregular surface, diameter  x x  cm, which originated from interatrial septum and prolapsed into the left ventricle through mitral valve during diastole (Figure ).Mild mitral regurgitation was found.Apical four-chamber section detected mild dilatation of the right atrium and Doppler echocardiographic examination registered the pulmonary arterial pressure up to mmHg.Since our patient had a low estimated risk of coronary arteries disease multislice computed tomography (MSCT) was done.With the results of MSCT we excluded hemodynamically signifi cant changes in the coronary arteries.Th e large tumor mass was also well visualized in the left atrium on both the axial slices and also with three-dimensional imaging (Figure ).Subsequently, the patient's left atrial mass was excised (Figure ) without complication and the mass was histopathologically confirmed as a typical myxoma.

Discussion
Cardiac myxomas are the neoplasms which have endocardial origin and are mostly found in the left atrium [].About  of all patients with the myxoma of this localization stay completely asymptomatic.The remaining patients can develop symptoms of mitral valve obstruction (), systemic embolization () and constitutional symptoms () [].In our patient mitral valve obstruction symptoms dominated (dyspnea), but also existed and constitutional symptoms (fatigue, myalgia and loss of body weight).Echocardiographic examination revealed a large tumor that almost completely obliterated mitral valve with subsequent mild mitral insuffi ciency and secondary pulmonary hypertension.Its presence was confirmed by MSCT.At the admission to hospital due to previously mentioned symptoms our patient did not have any symptoms of central or peripheral embolization.However, there was information about subarachnoid hemorrhage and operation of left PICA aneurysm being done ten months before.Intracranial aneurysms are rarely associated with cardiac myxoma.At the end of the nineteenth century Marchand was the first author who described this phenomenon [].Since then about forty cases of intracranial aneurysms associated with myxoma have been reported in literature.Sabolek et al. [] in the meta-analysis of  reported cases of cerebral aneurysm associated with myxoma found that patients were  to  years old, average about  years.In the analyzed group cerebral aneurysms were usually multiple, and were located in distal branches of both sides of middle cerebral artery.They were mostly fusiform-shaped ( cases), rarely saccular (), with the diameter  to  mm [].The data concerning the time of aneurysm diagnosis in relation to the detection of myxoma are different.The diagnosis of aneurysms varies from  years before the diagnosis of tumors up to  years after diagnosis [].In majority of patients aneurysm was discovered after cardiac surgery in the period from two months up to  years [,].Th e relationship between intracranial aneurysm and cardiac myxoma is still unknown.However, there are some hypotheses about the mechanism of their development [].According to the one of the theories, the origin of myxomatous aneurysm formation is embolization of the myxomatous cell to the intracranial vasculature with subsequent scarring, hemodynamic changes and pseudoaneurysm formation [].Another possible mechanism is the direct transendothelial pen-  etration and infi ltration of myxomatous tumor cells into the arterial wall which cause dilatation of arterial lumen by subendothelial growth.Th is theory is supported by some pathohistological studies which detect myxoma cells in the wall of aneurysms with interruption of the internal elastic lamina by invading tumor cells [].Alternatively, tumor cells may infi ltrate cerebral vessels via vasa vasorum, thereby destroying the architecture of arterial walls.Th is hypothesis is almost unacceptable because vasa vasorum mostly does not exist in intracranial arteries of experimental animals and humans [].Time is common factor for all previously mentioned mechanisms of aneurysm formation.That could be the reason for postponed aneurysm occurrence, even many years after the operation of myxoma.In presented case the intracranial aneurysm was detected before myxoma.Th is is not a rarity.Sabolek et al. [] found that in even  of patients intracranial aneurysm was detected before cardiosurgical resection of myxoma.Namely, it can be assumed that in the moment of appearance of neurological complications in our patient asymptomatic myxoma had already existed.Far more interesting is the fi nding of isolated intracranial aneurysm.However, even this rare fi nding with isolated aneurysm is not unique [].Furthermore, our patient had a saccular aneurysm while the most authors reported fusiform aneurysm.Besides the fi ndings of Sabolek et al. [] about the relationship between the saccular aneurysm and myxoma other authors have also fi nd these forms in combination with fusiform in patients with myxoma [, ].Specifi city is the localization at the PICA.As there are other aneurysms of rare and unexpected localization such as the basilar artery and the fact that the localization of the aneurysm at the PICA is not pathognomonic for atherosclerotic and congenital aneu-rysm [] we assume that there is a relation with the myxoma.In regard of the specifi city in our patient arises the question whether these are two independent entities or are they related?In the absence of histopathological confi rmation and other possible causes for peripheral aneurysms which include infection, tumor, choriocarcinoma embolization, trauma or Moya-Moya disease supports our assumption about the relationship between aneurysm and myxoma in this patient [].Th e natural history of intracranial aneurysms development in patients with cardiac myxoma is still unknown because coexistence of these entities is extremely rare.Roeltgen et al. [] have suggested that the clinical course of a myxomatous aneurysm has three possible forms: resolution after surgical removal of myxoma, potential progressive enlargement with possible hemorrhage, and spontaneous resolution or stabilization.Th at hypothesis was confi rmed in literature [,,].Th e poor experience in treating a small number of patients with this complication is the reason why treatment of intracranial aneurysms associated with cardiac myxoma is not precisely defi ned.As for one thing, appropriate and complete resection of myxoma is the method of choice because it minimizes the risk of tumor cell embolization but it does not eliminate the risk of delayed aneurysm formation regardless the mechanism of development -embolization or the metastatic way.There are no evidence-based guidelines that defined when cerebral angiography or aneurysm resection should be conducted in patients with cerebrovascular manifestations of atrial myxoma.Although fusiform aneurysms cannot be clipped because lack of a neck, successful surgical excision of these aneurysms has been reported [].The findings which confi rm that the dividing tumor cells are responsible for the formation of these aneurysms establish the hypoth-  esis that chemotherapy could prevent the aneurysm growth.However, results of doxorubicin therapy were equivocal [].In the case of our patient cardiac myxoma was not even considered as a possible reason for intracranial aneurysm development, since early diagnosis of myxoma was missed.Fortunately, there were no other complications in the meantime.In conclusion we must emphasize that intracranial aneurysm could be related with cardiac myxoma and could be the alert for prompt diagnosis of myxoma and tumor excision which consequently can prevent the other complications.

Declaration of Interest
Th ere is no confl ict of interest.

FIGURE 1 .
FIGURE 1. Conventional cerebral angiography showed saccular aneurysm arising from the origin of left posterior inferior cerebelli artery (2.4 x 3.1 mm).

FIGURE 2 .
FIGURE 2. TTE revealed a large polypoid tumor mass (7 x 4x 3 cm) prolapsed into the left ventricle through mitral valve during diastole.

FIGURE 4 .
FIGURE 4. Intraoperative view of the myxoma originating from atrial septum.