Convulsive Syncope From Carotid Sinus Syndrome as a Manifestation of Laryngeal Cancer

Introduction

The carotid sinus baroreceptors are found near the bifurcation of the internal and external carotid arteries bilaterally. They play a crucial role in regulating heart rate and blood pressure and do this by vagal parasympathetic innervation of the sinoatrial and atrioventricular nodes as well as inhibition of sympathetic tone to the heart and blood vessels. When stimulation of the baroreceptors causes a greater than expected reduction in heart rate and blood pressure, this is known as carotid sinus hypersensitivity (CSH). CSH has been defined as heart rate pauses of more than 3 seconds and a drop of systolic blood pressure of more than 50 mmHg by the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society and 2018 European Society of Cardiology syncope guidelines.^1,2 When CSH causes symptoms of cerebral hypoperfusion such as giddiness, syncope and falls, this is defined as CSS. Malignancies of the head and neck are an uncommon cause of CSS. ³ Treatment of the underlying malignancy often resolves CSS. ⁴

Case Report

A 62-year-old Chinese male with past medical history of hypertension presented with 3 episodes of syncope that occurred on the same day. These episodes lasted a few minutes with spontaneous recovery. There was no associated chest pain, palpitation, weakness, or abnormal movement noted. He was admitted to Cardiovascular Medicine. Initial electrocardiogram showed T-wave inversions in lead III but no arrythmias or prolonged QT interval was identified. Cardiac enzymes were trended and not found to be elevated. Echocardiogram revealed a normal ejection fraction of 60% with no valvular pathology. The patient was placed on telemetry monitoring which showed sinus rhythm, infrequent ectopic beats and no significant pauses. During that admission, the patient was noted to have hoarseness of voice and was referred to the Otolaryngology department. A full head and neck examination revealed small volume left cervical lymph nodes, with nasoendoscopy showing a left vocal cord palsy and left aryepiglottic fold tumor. CT neck performed showed a 2.4 × 3.6 cm left supraglottic tumor with thyroid cartilage destruction and extra-laryngeal spread. There was extensive cervical lymphadenopathy including a large 2.8 × 2.4 × cm necrotic lymph node lying in close relation and displacing the left carotid vessels laterally (Figure 1). Ultrasound (US) carotids showed compression of the left internal carotid artery by the large necrotic lymph node. The patient also underwent CT coronary arteries and was found to have severe stenosis of the proximal left anterior descending artery. In view of the raised anesthetic and surgical risk, panendoscopy and biopsy under general anesthesia was held off after discussion with the patient. Arrangements were made for CT guided biopsy instead. As the patient was clinically well, he was discharged while awaiting the biopsy appointment.

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Figure 1.

(A) Left supraglottic tumor measuring 2.4 × 3.6 cm. (B) Left retropharyngeal necrotic lymph node measuring 2.8 × 2.4 cm lying in close relation and displacing the left carotid vessels laterally at level of the carotid bifurcation.

Outpatient CT guided biopsy of the tumor revealed moderate to poorly differentiated invasive squamous cell carcinoma. Positron emission tomography (PET) CT showed hypermetabolic primary left supraglottic tumor and large, fludeoxyglucose (FDG) avid, rim enhancing left retropharyngeal and left level 2 to 4 cervical lymphadenopathy (Figure 2). A lesion in the superior mediastinum was ametabolic and suggestive of a pericardial or thymic cyst. The TNM staging for the patient was cT4aN2bMx, stage IVA.

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Figure 2.

CT neck performed as part of PET-CT 1 month after previous imaging. Left retropharyngeal and left level II necrotic lymph node surrounding the carotid bifurcation.

He then represented 3 days after PET-CT with pre-syncopal symptoms of giddiness and light-headedness. While admitted, he developed episodes of upper and lower limb jerking lasting seconds with loss of consciousness. These episodes were associated with significant bradycardia (heart rates ranging from 30 to 63 beats per minute) and hypotension (systolic blood pressure ranging from 41 to 89 mmHg). He was reviewed by Neurology and Cardiology departments and the patient was diagnosed with CSS secondary to supraglottic squamous cell carcinoma with cervical lymphadenopathy. CT and magnetic resonance imaging (MRI) brain were unremarkable. Electroencephalogram (EEG) showed no epileptiform activity. Inpatient telemetry monitoring revealed sinus bradycardia and intermittent junctional rhythm with heart rates less than 40 for longer than 10 seconds during the episodes. A trial of diazepam was not found to be effective in aborting the seizure-like episodes. Instead, measures to prevent and treat hypotension, such as maintaining adequate hydration, intravenous fluid resuscitation and dopamine infusion were effective. Subsequently, a permanent pacemaker was inserted and heart rate kept above 80 beats per minute. There were no further episodes of syncope or seizure-like episodes. Regarding definitive treatment of the supraglottic squamous cell carcinoma, after multidisciplinary tumor board discussion, the tumor was deemed surgically unresectable due to carotid encasement, and the patient underwent tracheostomy insertion and radiation therapy (RT). He was offered concurrent chemotherapy but declined due to the risks of side effects. He underwent RT for 3 sessions but defaulted subsequently as he was not able to lie flat due to secretions during treatment. 4 months post pacemaker insertion, there were no further documented episodes of syncope or seizure-like episodes. Unfortunately, the patient passed away soon after due to pneumonia.

Discussion

CSS is an uncommon condition and is found to be the cause of syncope in 1% of cases, ⁵ with an incidence of less than 1 in 250 among patients with head and neck malignancies. ⁶ The typical patient profile is a male greater than 65 years old. Furthermore, patients with hypertension and atherosclerotic heart disease have a greater response to carotid sinus stimulation. ⁷ Among the patients with head and neck malignancies presenting with CSS, the majority present with extensive cervical lymph node involvement, ⁸ as in the case of our patient. Common triggers of CSS include neck hyperextension, tight neckwear, coughing, straining, and heavy lifting. ⁹ It can be challenging to distinguish syncope from seizures, as syncope can also present as a convulsive disorder. ¹⁰ Convulsive syncope is uncommon with an estimated prevalence of 0.03%. ¹¹ It is caused by cerebral hypoperfusion whereas seizures are secondary to abnormal electrical activity in the brain. In our patient, given the presentation of jerking movements associated with hypotension and bradycardia, coupled with normal EEG and brain imaging, the seizure-like episodes were secondary to convulsive syncope masquerading as seizures.

Weiss and Baker ¹² first classified CSS into 3 subtypes: (1) The cardioinhibitory response which manifests as bradycardia and asystole. (2) The vasodepressor response which causes vasodilation and hypotension without bradycardia. (3) The cerebral response secondary to ipsilateral cerebral ischemia due to carotid artery compression. When these responses overlap, it is termed the mixed response. In a study of 132 patients over the age of 65 who were subjected to carotid sinus massage, 29% displayed cardioinhibitory, 37% vasodepressor, and 34% mixed response. ¹³ Our patient displayed a predominantly cardioinhibitory response.

The pathophysiology of CSS in head and neck malignancies is not yet fully understood and several hypotheses have been proposed. Firstly, direct tumor compression on the carotid sinus can cause reflex hypersensitization. ³ Secondly, the close proximity of the tumor to the carotid sinus can produce permanent depolarization of the axons, which creates a tendency to fire adjacent uninjured axons, causing CSS. ¹⁴ RT with post-irradiation fibrosis may also trigger CSS in a similar fashion. ⁸ Tumor invasion of the glossopharyngeal nerve causing neuralgia has also been described as a cause.^15,16 It is postulated that aberrant impulses originating from the glossopharyngeal nerve cause sympathetic inhibition and an abnormally strong carotid sinus reflex.^15,17 As such, in cases where carotid sinus massage does not induce syncope, one should consider the possibility of glossopharyngeal nerve involvement of the tumor.

Although stimulation of both carotid sinuses cause bradycardia, studies have shown a difference in response between the right and left. In a study by Sigler ¹⁸ of 345 individuals, it was found that stimulation of the right carotid sinus was associated with sinus bradycardia and sinoatrial asystole, whereas the left carotid sinus had greater association with high grade atrioventricular block (Mobitz type 2 and 3rd degree). For our patient, compression of the left carotid sinus produced sinus bradycardia and intermittent junctional rhythm. Atrioventricular block was not seen.

We postulate that CSS is a poor prognostic factor for patients with head and neck cancers. As discussed regarding the pathophysiology of CSS, tumors would have to be large and/or invasive to cause compression or invasion of the carotid sinus or surrounding nerves. In addition, the majority of such patients present with extensive cervical lymph node involvement. ⁸ In our patient, the primary supraglottic tumor was locally invasive with metastatic necrotic lymph nodes on presentation. The disease was advanced and surgically unresectable due to tumor encasement of the internal carotid and the carotid bulb. Our patient, who was only able to tolerate 3 sessions of RT, passed away just 6 months after initial diagnosis. As such, patients with head and neck cancers presenting with CSS are expected to have more advanced tumors, greater disease burden, a higher oncological stage and subsequent poorer prognosis.

In the management of CSS, the patient should first be educated on avoiding mechanical manipulation of the carotid sinuses. For example, the avoidance of wearing tight collars and chiropractic manipulation of the neck. Subsequently, anticholinergic medications and cardiac pacing can be considered and have been proven effective. ¹⁵ During syncopal episodes, atropine provides immediate symptom relief. ¹⁹ In patients, such as ours, who present with predominantly cardioinhibitory CSS, permanent pacemaker insertion is indicated.^1,20 However, for those with significant vasodepressor component of CSS, cardiac pacing is often ineffective. ⁴ Cardiac pacing can correct bradycardia and asystole but cannot address the vasodepressor response and vasodilation. Surgery is reserved for patients who fail medical therapy and pacemaker insertion. ²¹ This includes denervation of the carotid sinus by sectioning of the nerve of Hering or atherectomy with adventitial stripping. Intracranial sectioning of the glossopharyngeal nerve and upper 2 rootlets of the vagus nerve can also be considered. ²² When possible, definitive management is surgical removal of the tumor causing compression. ²³ In our case, the tumor was deemed unresectable and the patient was started on RT which has also been shown to be beneficial. ¹⁴

In conclusion, it is rare for laryngeal cancer to cause CSS. To our knowledge, this is the first reported case of laryngeal cancer manifesting as convulsive syncope masquerading as seizures due to CSS. In patients with unexplained syncope or seizure-like episodes and a background of head and neck cancer, clinicians should consider the diagnosis of CSS. CSS is a poor prognostic factor due to the associated higher stage of disease.