Rare cause of cardioembolic stroke and central retinal artery occlusion

Abstract

Primary cardiac valve tumours are rare. This is a case report of a 32-year-old non-smoker man with a history of stroke 1 year prior and no other cardiovascular risk factors. The patient was admitted to our acute stroke ward for recurrent left hemiparesis, slurring of speech, facial asymmetry and central retinal artery occlusion. Initial laboratory investigations and ECG were normal. An urgent CT brain showed a large hypodense area at the right frontal, parietal, temporal, occipital region with effaced sulci and right lateral ventricle with midline shift and cerebral oedema in keeping with acute infarction. We proceeded with CT angiography of the cerebral and carotid on the following day, which revealed no evidence of thrombosis, aneurysm or arteriovenous malformation. There were no abnormal beaded vessels to suggest vasculitis. Transthoracic echocardiography revealed a large mobile mass in the left atrium. Meanwhile, MRI cardiac confirmed a large ill-defined mobile solid mass attached to the mitral valve’s inferoseptal component suggestive of mitral valve myxoma. This case report highlights the significance of considering a cardiogenic source of emboli in patients with large cerebral infarcts and other cardiac embolic phenomena. Imaging modalities such as echocardiography and cardiac MRI will help detect treatable conditions, such as valvular myxoma and prevent further complications.

Background

Acute stroke in a young adult is uncommon, accounting for less than 1% of the general population.¹ The aetiologies and risk factors for arterial ischaemic stroke in young adults differ from those that are typical in older adults. Besides the atherosclerotic cardiovascular risk factors which are common in older adults, other risk factors should be worked up for the young stroke, including cardiac and haematological disorders, vasculopathy, illicit drug use, vasculitis and metabolic disorders.²

Cardiac tumour is a potential source of emboli to the central nervous system.³ Primary heart tumours are rare, while atrial myxomas are the most common benign primary neoplasm of the heart, accounting for close to 80% of all cardiac tumours.⁴ These neoplasms are typically located in the left atrium, where most of this tumour arose around the septal fossa ovalis margin (80%) as compared with the mitral valve area, which accounts for only 1% of cases.^{5 6} Symptoms include obstructive cardiac signs, embolic signs and systemic manifestations. In this case report, we present a case of a young adult with a cardioembolic stroke who was eventually found to have a large cardiac myxoma located at the mitral valve during our workup for his young stroke.

Case presentation

A 32-year-old man was referred from a district hospital, presented with acute onset left-sided hemiparesis, slurring of speech, facial asymmetry and difficulty in swallowing. He had a history of cerebral infarction a year before and was on single antiplatelet therapy. Otherwise, the man is a non-smoker, and he did not have any other medical illness. Clinical examination revealed bilateral ptosis with bilateral sixth cranial nerve palsy, left upper motor neuron seventh cranial nerve palsy, hemi neglect on the left side, moderate dysarthria and left hemiplegia with the power of 0/5 on the left side. Cardiovascular examination revealed normal first and second heart sound with no added sound. There was also no carotid bruit. There was a relative afferent pupillary defect on the right eye. Meanwhile funduscopic examination showed a cherry-red spot over the macula area on the right eye with macula oedema in keeping with right eye central retinal artery occlusion. On systemic review, the patient denied a history of significant loss of weight, night sweat and loss of appetite. The rest of the systemic examination was unremarkable.

Investigations

Laboratory investigations, including FFull blood count, electrolytes and liver function were all normal. Connective tissue disease screening was also sent, and all results came back normal. ECG revealed sinus rhythm and no evidence of cardiac arrhythmias. CT brain showed a large hypodense area at the right frontal, parietal, temporal, occipital region with effaced sulci and right lateral ventricle with midline shift and cerebral oedema in keeping with acute infarction (figure 1). There are also areas of hypodensity in the brainstem in figure 2 explains the presentation of bilateral sixth nerve palsy and ptosis. We proceeded with CT angiography of cerebral and carotid on the following day, which revealed no evidence of thrombosis, aneurysm or arteriovenous malformation. There were also no abnormal beaded vessels to suggest vasculitis (figures 3 and 4). Transthoracic echocardiography (figure 5) demonstrated a huge mass inside the left atrium measuring 7.2–9.1 cm. The chamber was not dilated, and the ejection fraction was recorded at 65% with good left ventricular (LV) function. Subsequent cardiac MRI confirmed a large mobile solid mass attached to the inferoseptal component of the mitral valve with tumor-like movements during cardiac cycles measuring 40.2 mm (length) × 32.5 mm (width) × 33.2 mm (thick), isointense on T1-weighted images and high signal intensity on T2-weighted image suggestive of valvular myxoma (figure 6). The mass partially prolapsed into the left atrium during the LV systolic phase and partially prolapsed into the LV during the left ventricular diastolic phase which is commonly seen in cardiac myxoma.

Figure 1.

CT brain showed hypodensity over the right middle cerebral artery territory with oedema and mass effect.

Figure 2.

CT scan showed hypodensity over the central pons.

Figure 3.

Normal CT cerebral angiography showed no evidence of thrombosis, aneurysm or vasculitis.

Figure 4.

Normal carotid angiography showed evidence of thrombosis or dissection.

Figure 5.

Echocardiography finding showed a mass attached to the mitral valve.

Figure 6.

MRI cardiac showed a solid mobile mass attached to the inferoseptal component of the mitral valve.

Differential diagnosis

Cardiac thrombus, papillary fibroelastoma and infectious vegetation are different diagnoses that one must consider. A cardiac embolus resulting from cardiac arrhythmia or LV clot would give a similar history. However, the 12-lead ECG of this patient did not reveal any cardiac arrhythmia. Whereas, echocardiography and cardiac MRI did not show any intraventricular clot and delivered an excellent ejection fraction. Two-dimensional echocardiography can be used to differentiate between myxoma and thrombus, where the thrombus typically presents with a layered appearance and myxoma may have an area of echolucency within the tumour.

Papillary fibroelastomas are usually found on the aortic valve but can also be present on the other valve. It is the second most common primary cardiac tumour in an adult after myxoma. They have a central core with ‘arms’ extending from the base described as sea anemones.⁶ Transthoracic echocardiography showed well-demarcated masses and uniform echo density with oval or irregular appearance. Up to 50% of these tumours have a stalk, and a majority of them are <20 mm in diameter. Myxoma is generally well defined, smooth, lobular and often pedunculated with a size usually more than 1.5 cm compared with papillary fibroelastoma which usually appears small and <1.5 cm with motion independent from the standard valve and is located on the downstream side of the valve by a small pedicle.^{7 8} In this patient, there is a huge mass attached to the inferoseptal component of the mitral valve, which moves according to the valve movement.

Infective endocarditis should always be ruled out. It is usually associated with cardiac vegetations that appear as flakes or masses of various sizes.⁶ It generally is located on the upstream side of valves from transthoracic echocardiography, orbiting motion independent of valve motion, chaotic with amorphous shape.

Complications of infective vegetation includes pseudoaneurysm, paravalvular leak/regurgitation or abscess.⁹ However, this patient did not fulfil the Duke’s criteria to support the diagnosis. Clinically, he did not show any peripheral stigmata of infective endocarditis. Furthermore, other inflammatory markers were not elevated. Even though myxoma is the most common intracardiac neoplasm, other intracardiac tumours are also possible such as fibroma, papillary fibroelastoma, or malignant tumours, including rhabdomyosarcoma and angiosarcoma. These neoplasms would give similar findings on imaging, but a tissue biopsy should differentiate between them.

Treatment

The patient was treated for partial anterior circulation cerebral infarction, on the line of acute stroke care. He was admitted to an acute stroke ward for close observation and was also provided with supportive management. He was initially presented to the district hospital with acute stroke; however, that hospital did not have thrombolytic therapy service for acute stroke. By the time, he arrived at our hospital, it was out of tissue window for thrombolytic therapy, and we decided not to go for thrombolysis. Several new lines support the use of intravenous thrombolysis in a patient with beyond 4.5 hour of last seen well or wake-up stroke as seen in extend.¹⁰ However, the absolute benefit is modest, and this recommendation is not ready yet for routine application. The benefits of adjunctive thrombolysis in eligible patients with a late time window remain questionable.¹¹

Previously, the patient was already on aspirin before this stroke, however, he still encounters a stroke event despite compliance to antiplatelet. Data show that pharmacotherapy with anticoagulation or antiplatelet do not prevent the recurrent myxoma-related cerebrovascular event, and it is not an alternative to surgical excision.¹² No known medical modalities exist for valvular myxoma, and drugs are usually used to treat cardiac complications such as arrhythmias or heart failure. After cardiac myxoma has been diagnosed, surgical excision will be the best choice. For this patient, we do not treat him with anticoagulant due to lack of clinical evidence that recommends anticoagulant use as prevention for recurrent stroke in myxoma-related cerebrovascular events.

Due to the risk of additional embolic events, prompt surgical excision of a mitral valve myxoma must be done to benefit the patients. The patient was then referred to the cardiothoracic team for resection. Myxoma resection with mitral valve replacement (based on extend of involvement) is recommended to avoid complications in the future, such as additional cardioembolic stroke (tumour), cardiac complications like heart failure, recurrent syncope and arrhythmias. Unfortunately, the patient refused to resect the tumour despite explanations regarding risks and benefits by our cardiothoracic team.

Regarding the patient’s right eye central retinal artery occlusion, we referred him to the ophthalmology team, and he was treated conservatively. No active management for his central retinal artery occlusion and follow-up were given to assess the vision. Again, the definitive treatment will be surgical resection to prevent recurrent embolic eventss and may worsen the future vision.

Outcome and follow-up

Rehabilitation, including motor function, physiotherapy, speech therapy and occupational therapy, was started for the patient’s neurological deficit. The patient currently uses a wheelchair at home and was given rehabilitation appointments with the neurology team and ophthalmology team. The patient must comply with following up with serial examinations to detect a recurrent embolic event. The risk of recurrence in this patient is high because the patient is not keen on surgical resection. No standard protocol for surveillance was involved. However, we conducted follow-up sessions for 4–6 months duration with serial annual echocardiography for each visit.

Discussion

Primary heart tumours are rare, and the majority are benign.¹² It has a female predominance between the third and sixth decades of life. It can arise from any cardiac chambers, although 75% occur in the left atrium and commonly found between third and sixth decades of life.¹² Their location, size and mobility determine the clinical features of these tumours; and in a minority of cases, there are no symptoms at all.^{3 13} One-third of myxomas are friable and will increase their tendency to emboli causing the embolic phenomenon.¹⁴ The larger size of tumours mostly has a smooth surface leading to more cardiovascular symptoms, mainly secondary to obstruction of AV valves.³

Ninety per cent of atrial myxoma is sporadic, while the remaining 10% represents an autosomal dominant pattern characterised by multiple tumours known as the Carney complex involving cardiac and extracardiac tumours.¹⁴ It is rare to find cardiac myxoma to arise from the mitral valve. Most of the atrial myxoma (83%) are in the left atrial, and only about 12.7% are found in the right atrial. A review by Chakfé et al reported 27 cases of mitral valve myxoma with a combination of 21 clinical cases and 6 postmortems.¹⁵ In 2001, an additional 10 cases were updated into discussion of Choi et al’s mitral valve myxoma, which is more common in females with a mean age of 37.6±20.5 years. Our literature review found 57 studies of mitral valve myxoma in the adult population dating date back to 1871.¹³ The majority of these cases presented with embolic complications or syncope.¹⁵ For the patient in this case who was presented with recurrent stroke and embolic phenomenon, it is essential to differentiate this valvular mass from other valvular lesions as management will be significantly different. Other possibilities of valvular mass will be benign tumours like papillary fibroelastoma or infective endocarditis.¹⁶

Previous literature has shown that ischaemic cerebral infarction was the most common neurological complication, where the mobility, and not the size of the cardiac tumour, appears to be related to embolic potential.¹⁷ The middle cerebral artery appears to be more commonly affected.¹⁸ Compared with intramural tumours, valvular tumours are characterised by greater mobility and a more significant tendency to embolise by way of tumour fragments or thrombus formed around the tumour.¹⁹ In our case report, this patient did not only suffer from ischaemic stroke; he also had ipsilateral central retinal artery occlusion as a result of cardioembolism of the tumour.

Echocardiography is very helpful in the evaluation of a suspected valvular tumour in determining the location, size, attachment, and influence on valve function, like in this case. It is non-invasive and widely available, making it a preferred choice in the initial cardiac tumour evaluation. We also can assess dynamic doppler flow due to cardiac myxoma. Transesophageal echocardiography is superior to transthoracic echocardiography in the diagnosis and characterisation of cardiac mass lesions.²⁰ MRI cardiac and CT give us additional information in assessing cardiac mass as they provide better resolution. For further description of mitral valve myxoma, between MRI and CT cardiac, MRI with contrast is the preferred option. In this case, we proceeded with cardiac MRI, which helped us to provide more information such as tissue characterisation, demarcating tumour size, attachment and its mobility. All this information helped us to diagnose valvular myxoma and differentiate it from other cardiac tumours, infective endocarditis and cardiac thrombus. This information may be further used during surgical resection. However, the diagnostic accuracy remains low at 68%, compared with the histopathological examination’s gold standard.^{12 13} Stellate cells with eosinophilic cytoplasm and indistinct border are histopathologic identification for cardiac myxoma.

Cerebral infarction with concomitant retina artery occlusion is usually related to embolic events due to various aetiology. Mitral valve myxoma can lead to multiple embolic events, and it can also be misdiagnosed as cardiac embolus.¹¹ In this case, there are no risk factors for ischaemic cerebrovascular events or atrial fibrillation. Nevertheless, intracardiac thrombus should be considered. Other than cardiac thrombus, there are reported cases of infection that can cause cerebral infarction with concomitant retina artery occlusion. Infection such as mycoplasma pneumoniae, which commonly causes respiratory tract infection, is also associated with extrapulmonary, including neurological manifestations.²¹ Other infectious agents include Varicella zoster virus, chlamydia pneumonia, mumps, influenza A and parvovirus B19 virus. In young patients, systemic causes such as autoimmune disease and hypercoagulable state also need to be considered in patients with acute stroke with concomitant retina artery occlusion. In the current case, there is no history to suggest acute infection prior to the event. Furthermore, systemic examination and blood parameters did not reveal any sign of autoimmune disease and a hypercoagulable state.

Once diagnosed, the treatment of choice would be surgical removal of the tumour as described in our literature, and the long-term prognosis was proven to be excellent.²² Early surgical intervention is vital to reduce having recurrent embolisation phenomenon. Embolic complications or sudden death are always possible, even in asymptomatic patients.

In summary, the valvular myxoma is rare, and it places the patients at a high risk of stroke and other cardioembolic events in different ways. Our case report has demonstrated how this valvular myxoma has caused recurrent strokes and central retinal artery occlusion within less than 18 months. The development of non-invasive diagnostic tools, such as echocardiography, CT and MRI, should be used to identify and evaluate valvular tumours. Subsequent cardioembolic events could be prevented if echocardiography is done during the first stroke attack. Therefore, clinicians must detect the tumour and prevent its complications.

Patient’s perspective.

On that day, I suddenly could not move my body’s left side, and my son said my voice has changed. I could not eat well and had double vision. I was hospitalized and admitted to the Intensive Neurology Ward. To my surprise, my doctors said that I have a growth inside my heart that needs to be removed. However, I was afraid of surgery, so I refused surgical intervention.

Learning points.

• Transthoracic echocardiography is an essential tool that can be used to investigate aetiology for young patients who had a stroke.

• It is important to consider a cardiogenic source of emboli in patients with large cerebral infarcts and other cardiac embolic phenomena for recurrent stroke with no traditional risk factor.

• Surgical intervention is the definitive treatment in patients with embolic stroke and cardiac tumour.

• Multiple infarcts in different vascular territories are a clue to a cardiogenic source.

• Early echocardiography will help to detect the cardiac myxoma and subsequent cardioembolic events that could have been prevented.