Clinical Reasoning: A misdiagnosis of atypical trigeminal neuralgia

Section 1

A 47-year-old man presented with right-sided facial pain that started 2 years prior. He described the pain as extremely intense, stabbing along the right jaw, lasting 5–60 seconds. This pain was exacerbated by chewing, and to a lesser degree, by brushing his teeth. The pain was so intense that he avoided eating when possible, leading to a 20-pound weight loss. When he did eat, he would try to chew on the left side of his mouth. Around the onset of these symptoms, he also noticed a persistent numbness and burning extending from the right lower earlobe to the lateral angle of the jaw that was exacerbated by turning his head to the right.

The patient was given a diagnosis of atypical trigeminal neuralgia (TN) and sent to our headache clinic for further management.

Section 2

TN is characterized by “recurrent paroxysms of unilateral pain in the distribution(s) of one or more divisions of the trigeminal nerve,”¹ most often the maxillary and mandibular divisions. As outlined by the International Classification of Headache Disorders, 3rd edition, TN pain¹:

• A. Does not radiate beyond the trigeminal distribution

• B. Lasts from a fraction of a second to 2 minutes (recurrent paroxysms may occur in clusters lasting longer)

• C. Is severe in intensity and electric shock–like, shooting, stabbing, or sharp in quality

• D. Is precipitated by innocuous stimuli within the trigeminal nerve distribution

Patients tend to be asymptomatic between paroxysms, though a subset of patients may develop a prolonged continual background pain, with fluctuations in intensity and periods of remission and recurrence that parallel the paroxysmal pain.² Approximately 99% of patients with TN report at least some of their attacks being associated with a trigger.^2,–,4 In one large study, the most commonly described triggers were gentle touching of the face (83% of patients) and talking (59%), followed by chewing (41%) and tooth brushing (36%).³ When cutaneous triggers are present, the most common trigger zones are around the mouth and nose, though anywhere on the face may be described.^3,5 Some patients may notice a transient refractory period following a paroxysmal pain, where additional pain cannot be triggered.¹ In contrast to the classic paroxysmal, shooting, stabbing, or shock-like qualities used to describe neuralgic pain, neuropathic pain tends to involve more persistent burning, tingling, or numbness. If the patient has features of neuropathy (numbness), persistent pain, bilateral pain, isolated supraorbital involvement, or a lack of sensory triggers, an alternative diagnosis should be considered. This could include dental pathology, parotid pathology, or an alternative neuralgia/neuropathy. See the table for a comprehensive overview of conditions that may mimic TN.

Our patient described paroxysmal severe shooting facial pain, lasting seconds at a time. He reported innocuous triggers, including chewing and possibly brushing his teeth. Interestingly, however, he denied all other classical TN triggers, including cutaneous triggers. He also described an atypical persistent pain that was more neuropathic (numbness/burning) than neuralgic, and this extended over the angle of the jaw and into the pinna of the ear, both territories that are outside of the distribution of the trigeminal nerve. Given the atypical presentation, we were concerned about an alternative diagnosis.

Section 3

A careful history is essential in the diagnosis of lower facial pain and should include the following:

• Head/neck surgery or trauma

• Cancer and systemic symptoms (fever/chills, night sweats, weight loss)

• Dental disease/procedures

• Symptoms suggestive of sympathetic pathway injury (ptosis or miosis)

• Clicking or popping of the jaw

• Rash (vesicles)

• All aggravating/relieving factors: swallowing, yawning, chewing, movement of temporomandibular joint, light touch, cool breeze or cold, head/neck positions, straining, talking, brushing teeth

On further questioning, our patient recalled a surgery just prior to the onset of pain, involving resection of a parapharyngeal pleomorphic adenoma for which he underwent resection via a right cervico-parotid approach. Follow-up MRI and magnetic resonance angiography revealed no tumor recurrence or other pathology to explain his neuropathic symptoms. On an extensive review of his triggers, he explained that while chewing on the right side did consistently trigger severe pain, if he could “push through,” the pain would subside after a minute, raising the question of a TN refractory period. Most interestingly, however, he also revealed that just thinking about food or smelling food could trigger similar severe pain. With regard to the constant burning pain over the angle of the jaw and ear, this was milder and did not fluctuate with his paroxysmal pains.

On examination, our patient had reduced pin sensation over the right lower ear extending along the angle of the jaw. Given the unusual triggering of pain with food smells, we performed a bedside provocation of salivation by giving the patient a sour candy. Even before putting the candy in his mouth, the patient began to experience his typical paroxysmal stabbing pain. This became severe when he put the candy in his mouth, prior to any chewing. After chewing for about 5 seconds, the excruciating pain settled back down to his constant numbness and burning. The remainder of his neurologic examination was normal.

Section 4

Our patient likely had 2 different diagnoses. The stabbing pain brought on by salivation and relieved after chewing for a few bites was consistent with a diagnosis of first bite syndrome (FBS). FBS is a known potential complication of surgeries in the parapharyngeal or upper cervical region, especially when there is damage to the sympathetic chain.^6,7 FBS can also occur with other injury to the sympathetic chain, including cervical arterial dissection or tumor invasion. The pain is typically described as a severe cramping or electric shock–like pain occurring in the region of the parotid gland and mandibular angle that occurs with the first bite of each meal and diminishes over the next several bites.⁸ Acidic or sour food may be particularly strong triggers for pain.⁶ Given the prominent trigger with salivation, it may be helpful to perform a bedside provocation of salivation, as we did in this case. Other than this bedside test, the neurologic examination in isolated FBS is often normal unless there has been damage to the sympathetic pathway. In this case, there may be an associated Horner syndrome, occurring in about 70% of patients.⁶

In the absence of ipsilateral upper neck or facial surgery, diagnostic imaging should be completed to exclude cancer of the deep lobe of the parotid gland, submandibular gland, or parapharyngeal space. Initial negative imaging should be repeated, given reports of tumor becoming visible several months after the onset of pain.⁹

The pathophysiology of this syndrome is believed to involve sympathetic and parasympathetic dysregulation.^8,10 Sympathetic secretomotor innervation of the parotid produces a small amount of thick saliva that inhibits secretion, whereas parasympathetic secretomotor input produces a large volume of watery saliva that stimulates secretion.¹⁰ Loss of sympathetic innervation to the parotid gland leads to denervation of sympathetic receptors located on parotid myoepithelial cells, which also contain parasympathetic receptors.⁸ These receptors are hypothesized to become hypersensitive to parasympathetic stimulation, resulting in a very intense contraction of these myoepithelial cells at the first bite.⁸

Our patient's case was complicated by a concurrent diagnosis of great auricular neuropathy presenting as constant numbness and burning along the lower earlobe to the lateral angle of the jaw. The great auricular nerve is a peripheral branch of the superficial cervical plexus that wraps around the sternocleidomastoid, before dividing into 2 branches that provide sensory innervation to the lower ear and the angle of the jaw, often extending the length of the mandible to the lateral chin (figure). Its superficial location makes it vulnerable to traumatic and iatrogenic injury, especially following rhytidectomy (facelift), carotid endarterectomy, and other cervical surgeries.

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Figure Sympathetic and parasympathetic innervation of the parotid gland

The sympathetics are supplied by the sympathetic chain coming off of the superior cervical ganglion. The parasympathetic innervation comes off of a branch of the auriculotemporal nerve. The inset on the right shows the great auricular nerve wrapping around the sternocleidomastoid to provide sensory innervation over the lower ear and angle of the jaw. Our patient, like many patients undergoing surgery to the deep parotid region, had injury to both the sympathetics as well as great auricular nerve resulting in first bite syndrome with concurrent lower face numbness. Image used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.