EN - Glosspharingeal Neuralgia

Glosspharingeal Neuralgia

The anatomy in the case where the left retrosigmoid approach was performed is shown in the figure. In the middle, glossopharyngeal nerves 10-11 on the left, nerve 8 on the right. Nerve 6 is the blurred nerve in the background.

Glossopharyngeal neuralgia (GPN) is a very rare pain syndrome, unlike its counterpart trigeminal neuralgia. It produces a shooting pain, like an electric shock, in the sensory distribution of the auricular and pharyngeal branches of the glossopharyngeal (IX) and vagus (X) cranial nerves. The area of ​​involvement includes the ear, base of the tongue, throat, tonsillar fossa, and angle of the jaw. GPN is defined as a brief, unilateral pain that starts and stops suddenly and can be easily triggered by simple movements such as speaking, swallowing, yawning, and coughing. Touching the external auditory canal and the side of the neck may also cause pain. An episode may last anywhere from 2 seconds to 2 minutes and may occur up to 200 times per day. GPN typically occurs unilaterally, although some individuals have described bilateral involvement. Occasionally, GPN has been associated with episodes of syncope, bradycardia, and seizures. When these symptoms occur, GPN is renamed vagoglossopharyngeal neuralgia (VGPN) because of the associated vagus nerve involvement. Understanding the anatomy helps to better understand the symptoms and triggers of GPN. The glossopharyngeal nerve exits the medulla via the brainstem and exits the skull via the jugular foramen. The glossopharyngeal nerve has five branches. The tympanic branch provides parasympathetic innervation not only to the parotid gland but also to the medial surface of the tympanic membrane, middle ear mucosa, and superior eustachian tube. The stylopharyngeal branch innervates the stylopharyngeal muscle and elevates the pharynx during speech and swallowing. The pharyngeal branch provides sensory innervation to the pharynx. The carotid sinus branch, together with the vagus nerve, provides parasympathetic innervation from chemoreceptors in the carotid body and baroreceptors in the carotid sinus, which may play a role in the syncopal attacks that occur in VPGN. The glossopharyngeal nerve gives off terminal tonsillar and lingual branches that carry somatosensory and taste from the posterior third of the tongue. Glossopharyngeal neuralgia is diagnosed clinically, but diagnosis is often difficult due to its location, clinical features, and rarity. It may overlap with other cranial nerve etiologies, leading to misdiagnosis. GPN is often misdiagnosed as trigeminal neuralgia (TN) because it shares similar clinical features and affects adjacent areas. Typically, GPN produces pain on the left side of the body, while trigeminal neuralgia affects the right side. Bilateral pain and associations with multiple sclerosis are more common in TN. It is important to note that individuals can suffer from both GPN and TN, as the glossopharyngeal nerve communicates with the mandibular division of the trigeminal nerve. Although there are diagnostic difficulties, management of GPN is essentially the same as that of TN.

EPIDEMIOLOGY
Glossopharyngeal neuralgia is a rare condition, much less common than other cranial neuralgias such as trigeminal neuralgia. It accounts for only 0.2–1.3% of all cranial neuralgias, affecting 0.2–0.4 per 100,000 people per year, and has a solid incidence rate of 0.7 per 100,000 people. The incidence of glossopharyngeal neuralgia increases with increasing age, most commonly affecting adults older than 50 years. In a retrospective review of data on glossopharyngeal neuralgia published in 1981, 57% of the 217 cases studied occurred in patients over the age of 50, and 43% were affected between the ages of 18 and 50. Glossopharyngeal neuralgia occurs equally in both men and women regardless of gender, but is typically more common in women and on the left side. In the same study mentioned earlier, 74% of patients reported spontaneous remission of pain episodes, and only 17% had constant pain without relief. Eighty-eight percent of patients reported unilateral pain, while another 12% had bilateral pain in the sensory distribution of the glossopharyngeal nerve.

RISK FACTORS AND COORDINATIONS
Glossopharyngeal neuralgia, like trigeminal neuralgia, typically presents in individuals 50 years of age or older. GPN symptoms increase with age; Therefore, age is the primary risk factor for developing GPN. There does not seem to be a gender predilection for GPN, although it is more common in women affected by pain in the head and neck region and more common in women presenting with orofacial pain. Therefore, both men and women are equally affected by GPN. In some cases of GPN, patients have been found to have cardiovascular or neurological symptoms such as asystole, bradycardia, hypotension, syncope, seizures, and even cardiac arrest. These symptoms arise from overlapping connections with the vagus nerve. In rarer cases, patients may develop these symptoms in the absence of the classic pain symptoms of GPN, making diagnosis even more difficult. Other rare comorbidities include tinnitus, vertigo, involuntary movements, and neurovegetative phenomena; eruption, salivation and unilateral mydriasis.

CLINICAL PRESENTATION AND DIAGNOSIS
Clinically, glossopharyngeal neuralgia presents with acute, sudden onset, recurrent attacks of severe, sharp, stabbing unilateral pain in the areas of sensory distribution of the glossopharyngeal nerve, together with a branch of the sensory vagus nerves. These areas include the mastoid, back of the throat, back third of the tongue, back of the nose, eustachian tube and middle ear, tonsils and larynx. Patients may present with cough and hoarseness and have difficulty speaking and swallowing. The pain typically begins in the back of the tongue or throat and radiates to the jaw or behind the ear. Rarely, glossopharyngeal neuralgia may cause bradycardia, hypotension, systole and even asystole. The duration of these painful episodes varies from seconds to minutes and may occur several times during the day or night. Triggers for attacks of pain include, but are not limited to, tinnitus, sudden head movement, touching the gums, touching the outer surface of the ear, coughing, sneezing, swallowing, talking, laughing, or chewing. Glossopharyngeal neuralgia is typically diagnosed clinically after presenting with the symptoms listed above. The diagnostic test for glossopharyngeal neuralgia involves touching the back of the throat with a cotton swab, which causes severe pain and is then relieved by the application of a local anesthetic such as lidocaine or bupivacaine. This test is especially important in patients undergoing surgery to confirm the diagnosis of glossopharyngeal neuralgia. Once the diagnosis is made, the underlying cause of the pain is determined by a history of trauma, radiation therapy, previous surgery to the mouth and maxillofacial area, laboratory tests including CBC, CRP, erythrocyte sedimentation rate, and antinuclear antibodies, and finally imaging such as a CT scan, MRI, X-ray, or MR angiogram. An MR angiogram can help identify the posterior inferior cerebellar artery and help clarify whether vascular compression is the cause, as the artery loop curves upward and can compress the supraciliary fossa. However, if the anterior inferior cerebellar artery is compressed, surgery is required to formally diagnose glossopharyngeal neuralgia.

DIFFERENTIAL DIAGNOSIS
When a patient presents with acute onset, severe, sharp facial pain such as glossopharyngeal neuralgia, there are a number of diagnoses that are included in the differential diagnosis.

The list is extensive, and some of the differential diagnoses are discussed below. A thorough physical examination and a comprehensive history can usually narrow the differential diagnosis to make the diagnosis, but some form of imaging is often required to confirm the suspicion.

TRIGEMINAL NEURALGIA
Trigeminal neuralgia is characterized by sudden onset, unilateral, electric shock-like pain in the distribution of the second or third division of the trigeminal nerve. The pain is episodic and ends as quickly as it came. With an incidence of 4.3 per 100,000 people in the United States, it is one of the most common cranial nerve neuralgias, typically affecting older women. Because it is much more common, glossopharyngeal neuralgia is often misdiagnosed as trigeminal neuralgia. A thorough history and physical examination can help with the correct diagnosis.

SUPRAORBITAL NEURALGIA
Supraorbital neuralgia is a subtype of trigeminal neuralgia involving the supraorbital branch. It is a rare disorder that typically presents with the triad of: nonradiating forehead pain, tenderness over the supraorbital nerve when palpated, and relief of symptoms with nerve block. Any type of facial pain can fall into the differential diagnosis for glossopharyngeal neuralgia, but the pain associated with supraorbital neuralgia is different in character from that presented by glossopharyngeal neuralgia. Patients with supraorbital neuralgia typically have sensory dysfunction and are characterized by pain localized in or just above the eyebrow.

SUPERIOR LARYNGEAL NEURALGIA
Superior laryngeal neuralgia can be triggered by speech, swallowing, coughing, and yawning and, like glossopharyngeal neuralgia, can be associated with hoarseness and cough. Therefore, it is included in the differential diagnosis list. Pain can be evoked upon palpation of the superior laryngeal nerve at the entrance to the larynx. A physical examination in the clinic can help distinguish between pain associated with glossopharyngeal neuralgia and pain associated with superior laryngeal neuralgia.

NERVUS INTERMEDIUS NEURALGIA
Neuralgia of the nervus intermedius is a rare disease and, like glossopharyngeal neuralgia, presents with intermittent unilateral electric shock-like stabbing pain. However, it differs from glossopharyngeal neuralgia in that the pain is located deep in the ear. This pain may be associated with lacrimation, salivation, or taste disturbances. It is less common for glossopharyngeal neuralgia to present with shock-like pain deep in the ear, so a thorough history and physical examination may help narrow the distinction.

NASOCILIARY NEURALGIA
Nasociliary neuralgia, also known as Charlin syndrome, nasal nerve syndrome, and nasal ciliary nerve syndrome, presents as a sharp pain in the nasal and paranasal regions. This pain is typically elicited by palpation of the lateral aspect of the nostril. This neuralgia is rare and the pain radiates primarily to the brow, eye, nose, or jaw. Some associated symptoms include tearing, conjunctivitis, congestion, sneezing, and forehead erythema. Nasociliary neuralgia still presents with facial pain, but it affects different parts of the face than typical glossopharyngeal neuralgia.

OCCIPITAL NEURALGIA
Occipital neuralgia presents with paroxysmal or shooting/stabbing pain with deep, aching pain between episodes. Pain can be triggered by palpation of the occipital nerve, and local anesthesia may cause resolution of symptoms. Associated symptoms of occipital neuralgia include visual disturbances, ocular pain, tinnitus, dizziness, and nausea, and are therefore frequently misdiagnosed.

EAGLE SYNDROME
Eagle syndrome presents very similarly to glossopharyngeal neuralgia. It occurs when an elongated styloid process impinges on the branches and fibers of the glossopharyngeal nerve, causing the same symptoms. Imaging is necessary to distinguish primary glossopharyngeal neuralgia from glossopharyngeal neuralgia caused by an elongated styloid.

TEMPORAL ARTHERITIS
Giant cell temporal arteritis presents with headache, painless visual loss, jaw claudication, and fever. There will be some temporal artery tenderness on palpation, and the headache may occur for 2–3 months at a time. This is made easier in the differential diagnosis of glossopharyngeal neuralgia because of the character of the pain associated with glossopharyngeal neuralgia and how different it is from that type of pain, but it still needs to be considered in a patient presenting with facial pain. A sedimentation must be obtained to formally diagnose temporal arteritis.

JACOBSON'S NEURALGIA
Glossopharyngeal neuralgia may present with loss of sensation in the ear alone. This is known as the otic form of glossopharyngeal neuralgia and is often confused with Jacobson's neuralgia. Jacobson's neuralgia is a neuralgia of the tympanic branch of the glossopharyngeal nerve. It presents very similarly to glossopharyngeal neuralgia, but will require imaging to confirm the presence of a mass or other anatomic abnormality that could be causing compression of the Jacobson's nerve.

MYOFACIAL PAIN DYSFUNCTION SYNDROME
Myofascial pain dysfunction syndrome is a psychophysiological disorder related to the masticatory muscles. The pain worsens with jaw movement and presents as a dull, radiating pain. It is a different type of pain than glossopharyngeal neuralgia and is less likely to be a differential diagnosis, but it is still on the list because of the facial pain that occurs with this syndrome.

CLUSTER HEADACHE
Cluster headache may be the least likely on the differential diagnosis list, but it is still important to mention. Like glossopharyngeal neuralgia, cluster headaches are more common in women and present with unilateral facial pain, but have symptoms such as Horner syndrome, conjunctival injection, and epiphora. Attacks are longer than glossopharyngeal neuralgia, lasting 15-180 minutes instead of seconds to minutes, and attacks occur without any stimulation.

PATHOPHYSIOLOGY
Most cases of glossopharyngeal neuralgia are idiopathic in that no identifiable lesion can be found. Idiopathic causes may be the result of vascular decompression or central pontine dysfunction. A possible explanation for vascular compression of the glossopharyngeal nerve is the posterior inferior cerebellar artery (PICA) compressing the nerve at the level of the root entry zone as it leaves the medulla and jugular foramen. Demyelination and axonal degeneration of the glossopharyngeal and vagal cranial nerves may be other idiopathic causes of GPN.
Although less commonly attributed to GPN, some individuals may have these attacks of pain due to other causes. Secondary glossopharyngeal neuralgia may be associated with malignancies or lesions compressing the glossopharyngeal nerve. Tumors located within the cerebellopontine angle (e.g., schwannomas) compress the glossopharyngeal nerve as it exits the skull. Other important tumors that can cause nerve compression include laryngeal and nasopharyngeal tumors, skull base tumors, oropharyngeal tumors, and tongue tumors. Invasion of such tumors can cause swallowing or displacement of the glossopharyngeal nerve, which can worsen symptoms. GPN can also develop after radiation therapy. In addition, infections such as tonsillitis, pharyngitis, arachnoiditis, para pharyngeal abscess, and tuberculosis can contribute to the pain syndrome. Complications of certain surgical procedures (e.g., after tonsillectomy, neck dissection, and craniosurgery) postotomy) may cause disorders of the glossopharyngeal nerve. Eagle syndrome (elongated styloid process), Paget syndrome, and Sjögren syndrome may also be present with GPN. A published case report specifically describes bilateral Eagle syndrome as a cause of bilateral GPN. It is theorized that the elongation of the styloid process may irritate the glossopharyngeal nerve as it courses (which is medial to the styloid process in the neck). Additional secondary causes include vascular malformations, direct carotid puncture, choroid plexus overgrowth, dental extractions, carotid aneurysms, and occipital cervical malformations. GPN has a variety of etiologies; therefore, it is also important to perform a comprehensive imaging study to adequately exclude other pathologic processes.

TREATMENT/MANAGEMENT
The treatment of GPN must involve more than one medical specialty because there are important differential diagnoses such as Trigeminal Neuralgia, Temporal Arteritis, Jacobson's Neuralgia, Superior Laryngeal Neuralgia and Myofascial Pain Dysfunction Syndrome mentioned above. Although the medical management of these diseases is similar, surgical approaches after failed conservative treatment are very different and must be differentiated. The treatment of this disease can be divided into three different categories that can be initiated in any order according to severity. Treatment usually begins with a fairly conservative or pharmacological approach. If this is ineffective, minimally invasive treatment is sought and then surgery is the last resort. These treatments are discussed below.

MEDICAL/CONSERVATIVE MANAGEMENT
One of the first studies by Rushton et al in 1981 showed that an anesthetic can be applied locally at the level of the oropharynx, which can be both diagnostic and therapeutic for GPN. In the past, medical cocaine was used in addition to anesthesia and GPN was diagnosed when the pain subsided. This is an option for those with acute symptoms who want immediate relief, although it may provide short-term relief of pain. Positive symptom relief from local anesthetics is predictive of future surgical intervention if medical therapy fails. This study also showed that carbamazepine was preferred by patients over phenytoin for relief of GPN symptoms. Pharmacological treatment for GPN is very similar to that for trigeminal neuralgia (TN) because of their similar but not widely understood pathophysiology, and both use anticonvulsants with sodium channel blocking mechanisms. Due to the similarity and lack of studies specifically targeting GPN, studies on TN treatments will be discussed briefly. A study in rats showed that carbamazepine had the most significant reduction in neuralgia-like pain compared with other similar drugs such as baclofen, clomipramine, and morphine. In a case study of a 48-year-old woman with GPN, a two-month trial of gabapentin treatment was shown to effectively stop her symptoms for four years, with no side effects from the medication. A group of researchers conducted a systematic review to determine whether eslicarbazepine acetate (a member of the dibenzoazepine family) would be a suitable alternative for the treatment of neuralgia in those who could not tolerate first-line treatments such as carbamazepine. One case study they reviewed showed that a woman with TN (bilateral from multiple sclerosis) was able to control her pain with carbamazepine. Unfortunately, she had significant side effects (symptomatic hyponatremia) that caused her to stop taking the medication. However, after trying several different medications, she was able to control her pain with no side effects using eslicarbazepine acetate (400 mg). Another study retrospectively reviewed patients with neuralgia-type pain (5 with TN, 3 with painful diabetic neuropathy, and 2 with postherpetic neuralgia) and showed that patients had a 50% reduction in pain on a visual analog scale (VAS) after treatment with an average dose of 800 mg eslicarbazepine per day. Although several studies showed promising results, the review article concluded that most of the studies did not have a control group and did not have a sample size large enough to support the use of eslicarbazepine as a good alternative to carbamazepine in the treatment of neuralgia pain. Another case study showed a 78-year-old man with symptoms of glossopharyngeal neuralgia for 2 years who was shown to have symptoms treated with 1800 mg gabapentin. Carbamazepine and oxcarbazepine had been tried but failed to control the pain in this patient. Although other drugs have been shown to work, first-line medical treatment continues to be carbamazepine or oxcarbazepine, and although patients experience pain relief, drug side effects are the main reason for discontinuation of treatment. In addition to these, pharmacological and conservative treatments, treatment mechanisms, additional treatments such as physical and psychological therapy, and h Both hot and cold compression have had varying success, but may be beneficial for some patients. If medical and conservative treatment fail, minimally invasive techniques are an option.

MINIMALLY INVASIVE OPTIONS
One minimally invasive treatment option for patients who do not respond to pharmacotherapy is pulsed radiofrequency (PRF). In this technique, radiofrequency pulses are directed to the affected nerve under CT guidance. This changes the way the nerve conducts electrical signals in a non-ablative manner to reduce the pain it may be causing. This has been proven to work in patients with GPN symptoms, but Jia et al (2020) conducted the first retrospective study to determine long-term outcomes. They concluded that, in the long term, pulsed radiofrequency is an effective and safe treatment option for those suffering from GPN. The study examined 25 patients with oropharyngeal carcinoma and over 3 months, PRF provided significant pain relief and improved sleep in 23 (92%) of the patients. They concluded that PRF is a promising method for reducing pain from GPN caused by oropharyngeal cancer. Another minimally invasive technique that can be used to reduce pain is a nerve block. Liu et al (2019) studied 12 patients with GPN who received a nerve block near the styloid process and concluded that it was a safe, ultrasound-guided treatment that provided significant pain relief for up to 18 months. Another woman with GPN secondary to postherpetic neuralgia experienced pain relief for several weeks after receiving a nerve block using 2 mL of 0.25% bupivacaine and 10 mg dexamethasone, followed by two more injections at 2 weeks and 4 months. The final minimally invasive technique to be discussed is percutaneous radiofrequency thermocoagulation (PRT), which has been used for many years as an effective treatment for pain of neuropathic etiology. Wang et al., after contacting 71 patients who received the treatment, determined that PRT was a safe and effective option for patients with GPN who could not be treated conservatively. They found that 78.8% of participants had pain relief immediately after the procedure and 43.0% had minimal or no complications 10 years after the procedure. Another retrospective study examining the same CT-guided PRT treatment examined 117 cases of GPN who had not achieved long-term relief with medical therapy or who had contraindications for surgery, and concluded that, apart from side effects (such as laryngeal and pharyngeal numbness, hoarseness, and dysphagia that resolved within 12.9 +/- 5.1 weeks), there was a significant reduction in pain (using the Barrow Neurological Institute pain scale), indicating that it was a safe and effective treatment option for some patients for up to 12 years. After trials of minimally invasive techniques, surgery is often the last resort for GPN, which is successful.

SURGICAL OPTIONS
The two main surgical options for treating glossopharyngeal neuralgia, which is indicated for patients who are resistant to or unable to receive medical therapy, are microvascular decompression (MVD) and rhizotomy. MVD is widely used for neuralgia-type pain, but until recently, the long-term outcomes of GPN treatment have not been studied. A group in Shanghai reviewed over 200 cases and reported that 86.9% of responding patients had “excellent” results after five years. Like any surgery, MVD carries potential side effects.
Another surgical treatment option for GPN is rhizotomy of the glossopharyngeal nerve. Ma et al (2016) retrospectively reviewed 103 cases of glossopharyngeal rhizotomy alone or in combination with partial vagus nerve rhizotomy. They found that although both were a safe and effective way to reduce pain associated with long-term pain relief for approximately 93% of subjects, the combination with vagus nerve rhizotomy had an approximately 9-fold higher long-term complication rate. In some cases, MVD may be tried in conjunction with rhizotomy in GPN. Rui et al (2019) compared the treatment option of MVD to glossopharyngeal nerve rhizotomy. They found that there was no significant difference in cure rates. They also found that patients with MVD plus rhizotomy had higher rates of complications such as cough and hoarseness associated with fluid intake. Their study suggests that adding rhizotomy to MVD does not improve the recovery rate of patients with GPN and may actually increase the risk of complications. One group also wanted to see if a rhizotomy was needed during/after MVD to provide adequate pain control. They found that MVD was sufficiently successful on its own, with 46 out of 46 patients experiencing immediate postoperative pain relief. They also found that 97.8% of them continued to have excellent pain control after 1 year.

CONCLUSION
Glossopharyngeal neuralgia, although rare, is a very common It is a complex pain syndrome that requires advanced treatment. Many different medical specialties are involved in the care of patients affected by glossopharyngeal neuralgia. These specialties include neurology, otolaryngology, interventional pain specialists, and neurosurgery. This review comprehensively summarizes the epidemiology, risk factors, clinical presentation, diagnostic criteria, differential diagnoses, pathophysiology, treatment, and clinical trials of glossopharyngeal neuralgia. Many other pathologies can present similarly to glossopharyngeal neuralgia, so definitive diagnostic measures are necessary to make a formal diagnosis. Treatment of glossopharyngeal neuralgia can be medical, minimally invasive, or surgical. Medical therapy typically includes carbamazepine or oxcarbazepine. If carbamazepine or oxcarbazepine does not sufficiently relieve the pain, other neuropathic pain medications may be prescribed. Glossopharyngeal neuralgia can also be treated with interventional pain management techniques, most commonly pulsed radiofrequency ablation, nerve blocks, or percutaneous radiofrequency thermocoagulation. There are two main surgical approaches that can be performed to treat glossopharyngeal neuralgia: microvascular decompression and rhizotomy. In general, glossopharyngeal neuralgia has a variable prognosis, as it is largely patient dependent.