Case of vago-glossopharyngeal neuralgia secondary to metastatic oropharyngeal cancer

Abstract

Glossopharyngeal neuralgia (GN) is a rare pain syndrome caused by compression of the glossopharyngeal nerve. It is typically idiopathic and often goes misdiagnosed because of its similarities to trigeminal neuralgia. Vago-glossopharyngeal neuralgia, an even rarer subset of GN, occurs when the pain is accompanied by syncope and/or arrhythmia. Here, we present the case of a 54-year-old man with oropharyngeal cancer that metastasised to areas within his left carotid sheath. He presented with numerous intermittent episodes of pain, accompanied by vagal episodes. While this presentation is similarly described in prior case reports, our case is unique in that the syndrome occurred as a direct sequelae of a metastatic tumour completely encasing the left internal carotid artery.

Background

Vago-glossopharyngeal neuralgia (VGN) is a rare craniofacial pain syndrome that is characterised by recurrent attacks of severe unilateral pain in the sensory distributions of the glossopharyngeal nerve and the auricular and pharyngeal branches of the vagus nerve.^{1 2} Patients typically complain of excruciating sharp, shooting or knife-like pain that lasts for several seconds to minutes. The pain is localised but not limited to areas such as the pharynx, submandibular area, palatine tonsils, middle ear and auricle.³ Other characteristics of this syndrome include syncope, hypotension and/or arrhythmias.⁴ Glossopharyngeal neuralgia (GN) alone has an annual incidence rate of 0.7 per 100 000 people and most frequently affects the left side of the head and neck in men over the age of 50 years.^5–8 Of those with reported GN, only 2% are said to have arrhythmias, hypotension or syncope during pain attacks forming the diagnosis of VGN.⁹ Current management of VGN includes the usage of antiepileptics such as carbamazepine and gabapentin.⁹ Surgical therapy is an option if medications cannot be tolerated or if the pain is refractory to treatment. Finally, temporary cardiac pacemaking has been trialled to prevent syncope with different outcomes.^10–14 Here, we present an unusual case of VGN secondary to a neoplasm causing complete encasement of the left internal carotid artery (ICA). This led to an atypical presentation of VGN with symptoms that included severe headaches, Horner’s syndrome and haemodynamic instability.

Case presentation

A 54-year-old man with a prior medical history significant for Human Papillomavirus-positive stage IV squamous cell carcinoma of the right tonsil status postchemoradiation in 2017 presented to an outside hospital with episodes of sinus bradycardia, hypotension and a painful left neck mass. He had been seen by his primary care physician for this neck mass 2 weeks prior and was subsequently started on oral prednisone and systemic antibiotics for a presumed ear infection. However, his symptoms did not resolve and he continued to experience left jaw pain as well as difficulty in swallowing. At the outside hospital, a CT of the neck was performed which showed encasement of the left internal carotid artery by a tumour. Additionally, a biopsy of the neck mass confirmed a poorly differentiated HPV-positive squamous cell carcinoma. CT and MRI of the brain were negative for acute pathology. At this point, the patient was transferred to our hospital for further workup and management.

On initial clinical examination, the patient was alert and oriented, answering questions appropriately and had no remarkable physical examination findings except for a tender left neck mass without surrounding erythema or fluctuance. He was found to be tachycardic and hypertensive with a heart rate of 113 bpm and a blood pressure of 180/114 mm Hg. His oxygen saturation was appropriate and his Body mass index was within normal limits.

After admission, the patient started having acute episodes of hypotension and bradycardia multiple times a day, without any obvious trigger. The patient described the episodes as starting with a sudden worsening of left-sided neck and jaw pain that radiated to the left temple and forehead, with associated nausea. At this point, his blood pressure and heart rate would drop rapidly, often necessitating a rapid response team. These episodes lasted approximately 5–10 min and would resolve with intravenous fluid boluses, pain and nausea medications and atropine. Following the episode, the patient would usually have one to two episodes of emesis after which the jaw pain and headache would temporarily resolve.

Investigations

Initial lab work was unremarkable except for mild euvolemic hypernatremia. Chest X-ray was unremarkable, and a CT with intravenous contrast confirmed no metastatic disease in the chest, abdomen or pelvis. Magnetic resonance angiography (MRA) of the brain and neck with and without intravenous contrast was performed under general anaesthesia to prevent any vagal episodes during the procedure. These studies revealed a mass centred within the left carotid space, circumferentially surrounding the mid/distal left internal carotid artery causing an area of mild narrowing but with the patent flow (figure 1). The mass extended from the level of the skull base to C3, measuring 5.5 cm craniocaudally, with extension posteriorly into the perivertebral and retropharyngeal space. MRA demonstrated significant narrowing of the left internal carotid by the mass (figure 2).

Figure 1.

Axial T2-weighted MRI through the suprahyoid neck demonstrates a mass (white arrow) within the left carotid space circumferentially surrounding the left carotid artery (circled).

Figure 2.

Magnetic resonance angiography demonstrates narrowing of the left internal carotid artery (arrow) by the mass.

Differential diagnosis

The initial differential diagnosis for the neck and jaw pain was an atypical migraine. The associated symptoms of nausea, vomiting, radiation of pain to the left side of the face and photophobia were thought to be consistent with a diagnosis of migraine. In regards to the episodes of bradycardia and hypotension, differentials included carotid sinus syndrome secondary to compressive effects from the tumour, psychogenic syncope as the patient had a diagnosis of chronic anxiety and vasovagal syncope triggered by emesis. Thus, the patient was given multiple doses of lorazepam, pain medication and antiemetics in an attempt to alleviate his symptoms and prevent recurrent episodes. However, episodes continued to occur despite these palliative measures and thus psychogenic syncope and vasovagal syncope seemed less likely differentials. After mapping the pain distribution, GN with a vagal component emerged as a likely diagnosis considering the patient’s sudden episodes of bradycardia and hypotension. The glossopharyngeal nerve is known to be directly connected with the nerve innervation of the carotid sinus, which could explain his vagal episodes. Additionally, the pain usually originated in the left neck and jaw over the glossopharyngeal nerve distribution. With the addition of nerve-inhibiting medications, the patient began to see some improvement of his symptoms, further pointing towards neuralgia as a likely diagnosis. Ultimately, VGN is mainly a clinical diagnosis; thus, it was the overall clinical picture that led to this diagnosis.

Treatment

Multiple treatment modalities were employed for the management of the patient’s vagal episodes. A cocktail of analgesics, anxiolytics, antiemetics and atropine were given at symptom onset. These would help symptoms resolve but they were in no way prophylactic against further episodes from occurring. In order to obtain MRI imaging to further characterise the carotid body tumour before the intervention, an isoproterenol drip was trialled. However, the patient had a vagal episode while on the drip, consequently suspending the procedure. We next tried a dopamine drip which in fact was able to maintain his heart rate and blood pressure during the study. Once the diagnosis of VGN was suspected, carbamazepine was initiated and titrated upward to control both pain and vagal episodes. The pain was controlled with a regimen of carbamazepine 300 mg two times per day, rizatriptan as needed and gabapentin 300 mg three times per day. In this case, the definitive management of VGN was by reduction of tumour burden. Radiation oncology initiated radiation therapy with curative intent. After 10 days of radiation, the patient experienced significantly fewer vagal episodes with no episodes for more than 3 days. However, his pain in the glossopharyngeal region did persist. This pain is expected to decrease in both frequency and intensity as the patient continues radiation therapy. A sphenopalatine ganglion nerve block was attempted to reduce the pain; however, the patient was not able to tolerate the supine positioning required and thus the procedure was terminated. Ultimately, the symptoms were unable to be controlled and it is suspected they will not be until a significant reduction of the tumour mass is achieved. After 2 weeks of radiation, the patient was free of vagal episodes for 3 days. His pain had decreased in intensity as well.

Outcome and follow-up

During his initial hospitalisation, a multidisciplinary committee came together to discuss possible long-term treatment options. While the surgical intervention was decided to be too high risk initially due to unstable vitals secondary to vagal episodes, the neurosurgical intervention was offered later which the patient refused. Thus, radiation-oncology was consulted for the initial reduction of his tumour mass, and treatment was initiated prior to discharge. Over time, the vagal episodes improved which seemed to initially indicate a small reduction in tumour burden surrounding the carotid. The patient’s chronic pain secondary to GN was partially relieved by medications such as carbamazepine and gabapentin.

Three months after hospitalisation, the patient did complete 66 Gy over 30 fractions using image-guided Volumetric Modulated Arc Therapy (VMAT) technique. Unfortunately, follow-up CT and Positive Emission Tomography (PET) imaging showed interval development of pathologic lymphadenopathy as well as an enlarged hypermetabolic right hilar lymph node at a size highly suspicious for nodal spread. Fine needle aspiration of the right hilar lymph nodes was positive for squamous malignancy. Six months postinitiation of radiation therapy, the patient was offered interventions such as radical surgical dissection to remove the malignant lymph nodes with the goal being curative or systemic therapy including immunotherapy and/or chemotherapy. However, the patient declined these options and chose to seek hospice care. His symptoms of GN continue to be managed medically as he continues to decline surgical options. He continues to report pain mildly alleviated by gabapentin and narcotic medications. Unfortunately, the pain will pervade as long as the patient continues to decline more invasive interventions.

Discussion

In conclusion, several mechanisms have been proposed to explain syncope with or without arrhythmia in the context of the glossopharyngeal syndrome. One of these proposed mechanisms is described as GN asystole syndrome, where arrhythmias and syncope develop due to the intense pain caused by neuralgia itself.¹⁵ In this phenomenon, abnormal stimulation of cranial nerve IX sends a combination of afferent fibres and collaterals to the dorsal medial nucleus of cranial nerve X.^{15 16} Other afferent signals are sent to the tractus solitarius causing activation of the parasympathetic nervous system leading to vagal effects.¹⁷ The Hering nerve is an afferent branch of the glossopharyngeal nerve that innervates the carotid sinus and carotid body located at the base of the ICA. Stimulatory signals received by the Hering nerve during episodes of neuralgic pain causes activation of the vagus via the mechanism stated above.¹⁷ This reflex loop causes episodes of bradycardia and cerebral hypoperfusion, which ultimately can cause syncope.¹⁸ Another mechanism involves invasion of the parapharyngeal space by tumours or abscesses. This case report was unique in that Cicogna et al reported that their patient did not present with any pain syndrome associated with GN, solely with syncopal episodes presumed to be caused by a lesion located in the parapharyngeal space. Similarly, in 2018, Nagata et al describe a case in which metastatic oesophageal squamous cell carcinoma caused the development of GN via metastasis to a parapharyngeal lymph node. Tumour infiltration was shown to directly cause the development of GN, and chemoradiation to reduce the tumour size completely resolved the symptoms.

In contrast, to the case described by Nagata et al, VGN likely resulted from the complete encasement of the ICA in our patient, causing compression of the glossopharyngeal nerve and altering vagal nerve transmission. Continuous changes sensed by the baroreceptors likely caused abnormal signals to be sent to the vasomotor centre of the brain which led to the patient’s haemodynamic fluctuations resulting in bradycardia and syncope. While VGN has been documented in medical literature since the 1980s, its mechanism remains poorly described. Management of this disease has been through trial and error, and there is no established protocol to guide providers on how to best manage these patients. VGN secondary to tumour burden/mass effect is even less documented and understood. Among the cases previously reported, there was no consistency of tumour location to accurately predict if the development of VGN will occur. However, it seems that patients with a history of oropharyngeal malignancy with new-onset syncope coupled with pain in the glossopharyngeal distribution may indicate tumour relapse and spread.¹⁹ VGN needs to be better described in order for a more timely diagnosis, which can not only reduce the morbidities associated with this syndrome but also diagnose tumour recurrence in patients with a history of malignancy. Overall, treatment and management of VGN, particularly in the context of malignancy, needs to be further studied as the options to date are only palliative and most patients with this disease, including our patient, continue with a very poor quality of life even after diagnosis.

Patient’s perspective.

For me, pain was the most debilitating symptom. When I would have those episodes these were actually welcomed for me because they would help my pain go away. My wife and I hope this diagnosis can be better studied and discussed in the literature because I do not want anybody to experience the same level of pain and suffering that I have been going through these past few months.

Learning points.

• Proper identification of this painful and debilitating disease is necessary to improve patients’ quality of life; however, identification is often difficult because of lack of awareness of the disease.

• Metastatic cancer may have several atypical/unexpected manifestations; thus, providers need to carefully assess the clinical picture beyond the presence of tumour burden.

• In complex cases such as this one, multidisciplinary teams need to be involved in patient care so that optimal treatment options can be offered.