Intermediate nerve neuralgia (INN), also called nervus intermedius neuralgia or geniculate neuralgia (GN), is a rare craniofacial pain syndrome that commonly causes severe unilateral pain in the external auditory canal (EAC) without any neurological deficits (1). The etiology of INN may be related to neurovascular conflict (NVC) or herpes zoster infection (2). The intermediate nerve (IN) contains three types of fibers: (1) general somatic afferent sensory fibers coming from the surface of the ear canal, tympanic membrane, retro-auricular skin, and regions within the pharynx; (2) special visceral afferent fibers coming from the anterior two-thirds of the tongue, floor of the mouth, and palate; and (3) general visceral efferent fibers innervating the lacrimal, sublingual, submandibular, and nasopalatine glands.

The IN exits the brainstem between the facial nerve and the vestibulocochlear nerve in the posterior cranial fossa before fusing with the facial nerve inside the internal acoustic meatus. Otalgia deep inside the ear can stem from the IN.

INN patients should begin with medical management, although the outcome is usually unsatisfactory, in which case, MVD or sectioning of the IN should be performed (3).

Here, we present a literature review and a case report to study the management of INN.

A woman in her early 60s with a remarkable medical history was admitted presenting with right otalgia and mandibular pain for 7 years. The right otalgia was located in the EAC, the auricle, and the deep part of the ear. The pain was described as a cutting-like sensation triggered by stimulation around the ear. It lasted from 10 s to several minutes and was occasionally accompanied by numbness at the base of the right tongue, which remitted spontaneously. The patient had a history of carbamazepine allergy and no history of ear herpes zoster infection. Prior to admission, she had undergone several acupuncture and physiotherapy sessions and had taken oral medications, such as mecobalamin and gabapentin, but with no significant improvement in symptoms. Physical examination did not show any unusual symptoms but the aforementioned pain. On admission, the patient had a Barrow Neurological Institute (BNI) pain intensity score of IV and a numerical rating scale (NRS) score of 9.

INN is an uncommon cranial neuralgia syndrome. Its etiology remains unclear, although neurovascular compression of the IN is the most likely cause of this kind of otalgia. This otalgia is usually triggered by stimulation of the posterior wall of the EAC or periauricular region, which is usually caused by NVC with the IN by the AICA.

INN is difficult to diagnose directly; hence, diseases that are similar to INN should be eliminated first. These diseases include otitis externa and media and intracranial lesions in the cerebellopontine angle; malignancy of the pinna, EAC, temporal bone, or nasopharynx; temporomandibular joint diseases; lesions of dental origin; referred pain from nasopharyngeal and laryngeal lesions; vascular lesions; and rare syndromes, such as Eagle's syndrome (6). To eliminate all these causes of otalgia, the clinician should perform thorough neurological, dental, otological, and other ENT examinations.

To diagnose INN, differentiating it from other kinds of neuralgia, especially neuralgia supplied by cranial nerves V, VII, IX, and X, is essential. The two diseases most easily confused with INN are trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN) because both are similar to INN in their pain characteristics. The location and distribution of the pain contribute to the differential diagnosis.

EAC pain can also occur with TN and GPN. Therefore, we need to gradually investigate the source of pain according to the diagnostic criteria (4). TN is the most common cause of facial pain. The typical location of the pain in TN is the second (maxillary) or third (mandibular) division of the trigeminal nerve. The right-side pain is usually mild, and the right side is also more likely to be affected than the left side (7). The most frequent trigger actions are touching the face, talking, chewing, and brushing teeth, while unusual trigger actions include flexing the trunk, contact with hot or cold food/water, speaking loudly, and turning the eyes to the right (8).

GPN is characterized by momentary, spasmodic, and acute stabbing pain in the posterior area of the throat, tonsillar fossa, base of the tongue, ear canal, and areas inferior to the angle of the mandible. GPN usually persists for several seconds and is triggered by swallowing, chewing, talking, coughing, or yawning. This kind of pain often overlaps with the pain of INN. Using local anesthesia to block local nerves in sequence may help identify the nervous origin (9).

To diagnose and assess patients with INN, 3.0 T MRI of the cerebellopontine angle is important. This may identify vascular compression of the nervus intermedius, although the positive rate is not 100%. In addition, vascular nerve compression cannot diagnose INN because many asymptomatic patients also have vascular nerve compression (10). However, the most important diagnostic criterion is an operative picture showing that neurovascular compression on the nervus intermedius is essential for the diagnosis of intermediate neuralgia.

Other investigations, such as auditory evoked brainstem responses, pure-tone audiometry, vestibular function tests, and computed tomography, can also help exclude other causes of otalgia.

All patients with INN should begin medicinal therapy, which is the first-line treatment for INN with varying success (11). Carbamazepine, lamotrigine, gabapentin, and tricyclic antidepressants, such as amitriptyline, are commonly given to patients with INN. Carbamazepine is the most commonly used medicine for INN and the most likely to achieve good clinical outcomes (12). The daily dose of carbamazepine ranges from 200 mg to 1,800 mg according to the patient's tolerability and sensitivity (13). The long-term use of carbamazepine will lead to low bone mineral density. Carbamazepine can also decrease the plasma concentration of warfarin and other drugs. Common side effects include, but are not limited to, tiredness, dizziness, ataxia, nausea, hyponatremia, and leucopenia (14).

Other medicines for the treatment of INN include oxcarbazepine (300–2,700 mg), lamotrigine (25–800,000 mg), gabapentin (300–3,600 mg), pregabalin (150–600 mg), baclofen (5–100 mg), phenytoin (50–500 mg), and botulinum toxin type A (25–195 units). Considering that these drugs have different sites of action, combinations of medicines for the treatment of INN may be better than single-drug therapy and can also treat patients who have single-drug resistance.

Regional nerve blockade through local anesthesia is an alternative to medical therapy. Many investigations suggest that local anesthesia is effective for all kinds of neuralgia, even beyond the period of conduction blockade, which means that all patients with ineffective drug treatment should receive regional nerve blockade before surgery.

When medicines and regional nerve blockade fail, surgery should be considered. There are many procedures for the treatment, but the most common forms of operation are MVD and intracranial sectioning of the nervus intermedius (15). We present herein a summary of previous papers on the surgical treatment of INN (Table 1). We found that with a deeper understanding of INN, the surgical treatment of INN gradually changed from transection of the IN to MVD combined with transection of the IN. The surgical methods selected in our case refer to the previous literature and verify and supplement them, which is believed to have a good reference value for subsequent INN patients (16–23).

Surgical treatment is an optional treatment for INN. There are two widely used options, namely, MVD of the IN at its REZ and transection of the nervus intermedius. MVD of the nervus intermedius is a surgery that relieves the vascular compression at its root entry area to the brainstem if there is a tortuous vascular loop. Usually, the compressing vessel is the AICA or the vertebral artery. This procedure aims to separate the nervus intermedius from the compressing vessel by inserting a piece of Teflon as MVD for TN. However, unlike the clinical efficacy of MVD for TN, there is still a lack of evidence to support the efficacy of MVD for intermediate neuralgia (24). Kenning et al. (25) performed and described MVD for intermediate neuralgia in detail.

Sectioning of the nervus intermedius is a surgery that directly cuts off the IN. This kind of operation can effectively relieve or even cure neuralgia. However, considering that the IN is composed of three kinds of fibers (26), transection of the IN may lead to a corresponding loss of nerve function. A number of case reports suggest that, even if transection of the IN relieves the pain, this surgery has some complications, including, but not limited to, cerebrospinal fluid leak, paresis of the ninth and tenth cranial nerves, facial paresis, facial numbness, chemical meningitis, and wound infection (27, 28). In addition, NVC may not be found by 3.0 T MRI. The patient's change from fear of the disease to understanding and relaxation now further proves the effectiveness of our treatment.

Considering that INN is similar to TN and GPN, the diagnosis must be made after these diseases are excluded. At present, special MRI sequences are an important choice for the diagnosis of the disease for their ability to find neurovascular compression of the complex of the seventh and eighth cranial nerves; however, this imaging manifestation must be combined with clinical manifestations to be meaningful because many asymptomatic patients also have this imaging manifestation. In addition, there are many patients with clinical manifestations without obvious imaging abnormalities, which makes the diagnosis of INN very difficult. More studies focusing on the etiology of INN are warranted.