Top-of-Basilar Artery Occlusion Thromboembolism in Arrhythmogenic Right Ventricular Cardiomyopathy Treated with Intravenous Thrombolysis and Mechanical Thrombectomy

Acute thromboembolic ischaemic stroke is a recognized complication of arrhythmogenic right ventricular cardiomyopathy (ARVC). While the precise mechanisms underlying the increased risk of stroke in ARVC are not fully understood, potential contributing factors include concomitant atrial fibrillation (AF) and the formation of intracardiac thrombi [1].

Stroke involving the basilar artery region accounts for less than 10% of all ischaemic strokes and presents with a wide range of non-specific clinical symptoms and signs, posing difficulties for clinicians to recognize. Patients often end up with poor outcomes without receiving recanalization therapy in time. Therefore, a high index of suspicion and the crucial role of computed tomography (CT) angiography in detecting occlusive thrombi is required for these time-sensitive therapies such as intravenous thrombolysis and/or endovascular thrombectomy (EVT) [2].

The management of ARVC-associated thromboembolic complications necessitates a multidisciplinary approach, involving comprehensive cardiac evaluation to assess ventricular function, arrhythmias, and the presence of intracardiac thrombi. Additionally, strategies for stroke prevention, such as anticoagulation therapy with direct oral anticoagulant (DOAC), may be indicated based on individual patient characteristics and risk profiles. By exploring the complexities of ARVC and its thromboembolic complications, along with the critical recognition of posterior circulation stroke, specifically top-of-basilar artery occlusion (BAO), we aim to contribute to a better understanding of this rare but clinically significant condition and improve patient outcomes through targeted interventions and preventive measures [3].

A 37-year-old man presented to the emergency department with acute onset of dizziness, imbalance, and vomiting. He described the dizziness as a persistent spinning sensation, rendering him unable to ambulate. He was in hospital when the symptoms began. His medical history was significant for hypertension and ARVC, for which he underwent implantable cardioverter-defibrillator (ICD) insertion in 2014. He also experienced ischaemic strokes in 2018 and 2019 with full neurological recovery following each event. He was followed up in another large cardiac centre and was prescribed aspirin and atorvastatin.

On examination, the patient exhibited a normal body habitus. Vital signs included a blood pressure of 144/86 mm Hg, a pulse rate of 88 beats per minute with a regular rhythm, a respiratory rate of 18 breaths per minute, and a temperature of 37°C. The neurological examination revealed bilateral ptosis, ophthalmoplegia, vertical nystagmus, and dysarthria. Coordination tests showed a notable left upper limb intention tremor and past pointing, along with a positive heel-shin test on the left lower limb. There was no limb weakness, no abnormalities in reflexes, and no abnormal sensations on proprioception and pinprick examinations. The National Institutes of Health Stroke Scale (NIHSS) score was 7. A non-contrast CT scan of the brain revealed no obvious hypodensity, with an Alberta Stroke Program Early CT Score (ASPECTS) of 10, while CT angiography and subsequently cerebral angiography detected an occlusive thrombus at the top-of-the-basilar artery as shown in Figures 1 and 2, respectively.

As his presentation was within 3 h of onset, he was treated with intravenous rt-PA at the dose of 0.9 mg/kg followed by EVT. Complete recanalization of the basilar artery was achieved using the Penumbra reperfusion catheter system, resulting in a modified Treatment in Cerebral Infarction (mTICI) score of 3 as shown in Figures 3 and 4. Post-procedural CT brain as shown in Figure 5 revealed a small area of cerebellar haemorrhage with intraventricular extension.

A transthoracic echocardiogram conducted a week later revealed a left ventricular (LV) ejection fraction of 30–35% with akinetic segments in the basal to mid anterolateral wall, hypokinetic segments in the basal to mid inferolateral, basal anteroseptal, basal inferoseptal, apical lateral and basal inferior wall regions. No intracardiac thrombus or significant valvular abnormalities were detected. A subsequent transesophageal echocardiogram was performed to further evaluate and confirm the absence of an LV thrombus and excluded a patent foramen ovale. Electrocardiogram monitoring indicated sinus rhythm with no arrhythmias detected during the inpatient stay. Magnetic resonance imaging of the brain as shown in Figure 6 which was performed 2 weeks from presentation revealed complete recanalization of the basilar artery thrombosis, late subacute cerebellar reperfusion haemorrhages with residual right intraventricular extension, and mild communicating hydrocephalus. ICD interrogation and 24-h ambulatory electrocardiogram monitoring did not show evidence of AF.

Clinically, the patient exhibited no focal neurological deficits except for horizontal gaze-evoked nystagmus. A multidisciplinary team concluded that long-term secondary prevention of stroke should involve initiating anticoagulant therapy with a DOAC. At the 3-month follow-up, the patient exhibited normal physical findings with no recurrence of stroke and was discharged with a modified Rankin Scale (mRS) of 1.

BAO is a rare condition, accounting for approximately 1% of all ischaemic stroke cases. In our case, the presentation is part of recognized manifestations of top-of-the-basilar syndrome. A high index of suspicion should be present as the failure to diagnose the condition promptly can lead to dire consequences.

Embolism is a well-known cause of distal BAO, as demonstrated in our case. Specifically, in cases involving the distal basilar artery, also known as top-of-the-basilar syndrome, individuals may present with progressive reduction in consciousness with oculomotor and pupillary dysfunction due to midbrain involvement. Another important consideration is that the NIHSS has limitations as it has emphasis for left-dominant hemisphere functions and the anterior circulation with lesser focus on cranial nerve dysfunction. As a result, a low NIHSS score may not accurately represent the severity of posterior circulation strokes. Overall, the diagnosis of BAO is challenging due to its non-specific clinical presentation, which varies according to the specific level of BAO [2].

The aetiology of posterior circulation strokes parallels that of anterior circulation strokes, encompassing atherothrombotic disease, small vessel disease, embolism, and, to a rare extent, arterial dissection [2]. Patients with posterior strokes may present with NIHSS score of 0 despite experiencing symptoms such as nausea, vertigo, or headache. This diagnostic challenge can lead to missed opportunities for timely intravenous thrombolysis or EVT, resulting in poor functional outcomes or death [2‒4].

ARVC is a rare autosomal inherited, idiopathic cardiomyopathy characterized by the replacement of myocardium in the right ventricle with fibro-fatty tissue and complicated by myocardial necrosis. The disease pathogenesis is related to desmosomal dysfunction where mutations in desmosomal proteins such as plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, and plakoglobin result in disruption of intercellular cardiomyocyte adhesion. This condition occurs with variable penetrance and clinical expression. The usual medical presentations include palpitations, syncope, and sudden death in young individuals between the ages of 20–40 years [5]. However, thromboembolic complications including ischaemic stroke were less commonly reported. One mechanism of stroke is altered haemodynamics and stasis of blood from wall motion abnormalities leading to thrombus formation. The other mechanism is cardiac conduction system disease contributing to the presence of AF and other arrhythmias [6]. LV abnormalities occur in the late stages of ARVCD as part of the disease progression although more recent literature and advances in understanding have identified ARVC patients with biventricular and LV dominant disease. Overall, LV failure and LV thrombus formation are more significant contributors to thromboembolic stroke than right ventricular (RV) disease. In our patient, the poor LV function is likely to be due to advanced disease in ARVC and also possibly, progression from a subset of the ARVC phenotype [5‒7].

Studies have indicated a 14% incidence of atrial arrhythmias over 5.8 years in patients with ARVC. AF accounts for approximately 70–80% of reported atrial arrhythmias [5]. The primary risk factor for developing AF in these patients was right atrial (RA) dilatation. Other associated risk factors include older age, male predominance, hypertension, and the presence of atrial flutter. Pathophysiologically, as clarified earlier, desmosomal dysfunction leads to RA dysfunction, which in turn causes RA enlargement and subsequent right heart failure. Further RA remodelling results in multiple re-entry circuits and substrate for the development of AF [5, 6, 8].

The therapeutic management of ARVC is challenging. Management options include lifestyle modifications, medications (antiarrhythmics, β-blockers, and cardiac failure medications), catheter ablation, ICD implantation, and, in severe cases, heart transplantation. Patients with ARVC are advised to avoid competitive sports, except for recreational, low-intensity activities. ICD implantation is recommended for individuals with hemodynamically unstable, sustained ventricular tachycardia or ventricular fibrillation, and for those with severe RV or LV dysfunction, regardless of the presence of arrhythmias. For incessant ventricular tachycardia or frequent ICD interventions despite optimal therapy, catheter ablation is advised [5]. In the case discussed, despite receiving an ICD implantation, the patient developed recurrent strokes, suggesting the potential presence of subclinical or paroxysmal AF as a causative factor. Anticoagulation therapy plays a pivotal role in secondary prevention of thromboembolic events in ARVC, particularly in individuals with AF or a history of neurovascular events [6].

In rare cases, given the lack of evidence from randomized controlled trials, guidance from retrospective studies has shown that patients with ARVC and RV thrombus had substantial thrombus resolution with the use of DOAC or warfarin [7]. On this basis, treatment was individualized. In our case, the current admission from a cardioembolic stroke was an indication for long-term anticoagulation with a DOAC as secondary prevention.

The use of anticoagulation in primary prevention of stroke in ARVC is recommended in the presence of AF and in individuals with significant ventricular dysfunction. The use of antiplatelet therapy is acceptable in the absence of these risk factors [5‒7]. In our case, the patient presented with a cardioembolic stroke with a history of prior strokes from another centre. In addition, the presence of large hypokinetic right and left ventricles with concomitant sluggish flow within the right ventricle detected by echocardiography is a recognized risk factor favouring the initiation of anticoagulant therapy [7‒9].

Our successful treatment of this patient was dependent on the timely recanalization through intravenous thrombolysis and EVT. These strategies have recently been proven in the setting of clinical trials which achieved favourable outcomes in cases of BAO [10, 11]. Without such interventions, the prognosis is poor, as reported by the Basilar Artery International Cooperation Study (BASICS) where 68% of patients had a poor outcome defined as a mRS of 4, 5, or death. Interestingly, this study also reported a considerable rate of successful or partial recanalization at 62.1% (64 out of 103 patients) but with time lines beyond that seen in our case report [12].

Patients with unsuccessful recanalization typically presented with longer thrombi (>10 mm) located at the midbasilar or less commonly at the top-of-the-basilar location [4]. These findings underscore the importance of timely thrombolysis and thrombectomy in BAO, as it achieves the highest recanalization rates for large artery occlusions and should be considered the initial therapy of choice [4].

This case underscores the importance of prompt recognition of the non-specific and varied symptoms of acute posterior circulation stroke syndromes as well as the limitations of the contemporary NIHSS scoring system. This case highlights the critical role of multimodal imaging techniques, such as CT angiography, in confirming the diagnosis of BAO and enabling timely therapeutic interventions like EVT and intravenous thrombolysis. Additionally, comprehensive cardiac evaluation is crucial for identifying underlying structural heart disease and potential sources of cardioembolism, particularly in cases involving the top-of-the-basilar artery segment. Long-term secondary stroke prevention strategies should be tailored to each individual based on their specific aetiology and comorbidities. In the continuum of the management of ARVC, the decision to initiate anticoagulation therapy with DOAC reflects a careful balance between reducing the risk of recurrent stroke and minimizing the potential for haemorrhagic complications. Overall, this case illustrates the intricate interplay between cardiovascular and cerebrovascular pathology and emphasizes the necessity of a multidisciplinary approach to optimize patient outcomes in acute stroke care of a complex patient with ARVC.

The authors would like to thank the medical, nursing, and interventional laboratory staff involved in the care of acute stroke patients at the University of Malaya Medical Centre.

Ethical approval was not required for this study in accordance with local guidelines. All relevant data were anonymized. Written informed consent was taken from the patient for the interventional procedures and for subsequent use of data related to publication and teaching purposes.

The authors have no conflicts of interest to declare.

No funding was received for this work.

The early drafts of the manuscript were written by Amirul Ab Ghapar, Grace Chu Sze Ern, and Ru Peng New. Khairul Azmi Abdul Kadir, head of biomedical imaging department and interventional neuroradiologist, performed the thrombectomy and provided the supervision for the technical description of the procedure and the labelling of pertinent radiological images. The members of the neurology team who were involved in the clinical management of this patient including the material preparation and analysis are as follows: Amirul Ab Ghapar, Grace Chu Sze Ern, Imran Idris, Sharon Mei Ling Tai, and Kay Sin Tan. Goh Khean Jin was the head of the neurology unit at the time and co-managed the patient. Ru Peng New and Imran Zainal Abidin provided the inpatient cardiological input for this patient. Kay Sin Tan as senior and corresponding author provided guidance for amendments and revised the final manuscript for clarity and critical content. All authors read and approved the final manuscript.

The data that support the findings of this case report are not publicly available due to the confidentiality surrounding the doctor-patient relationship as the information could compromise the privacy of the participant. However, upon reasonable request, it is available from the corresponding author.