INTRODUCTION AND DEFINITION — Neuralgia is a form of neuropathic pain that is characterized by the following features [1-3]:

●Paroxysmal, brief (seconds to a few minutes), shock-like or lightning-like pain that follows a peripheral or cranial nerve distribution and can spread to adjacent areas in the course of the attack.

●By definition, no objective neurologic deficits are found in the distribution of the affected nerve. (See "Overview of craniofacial pain".)

●Attacks can be provoked by nonpainful stimulation (allodynia) of trigger points or zones.

●A refractory period follows attacks; the duration of the refractory period shortens as the disease progresses.

Nervus intermedius neuralgia is a rare disorder characterized by brief paroxysms of pain felt deeply in the auditory canal [4]. Other terms previously used for this condition used are geniculate neuralgia and Hunt neuralgia [5].

This topic will review clinical aspects of nervus intermedius neuralgia. Other cranial neuralgias and central causes of facial pain are discussed separately. (See "Overview of craniofacial pain" and "Central neuropathic facial pain" and "Cold stimulus headache" and "Nummular headache" and "Occipital neuralgia" and "Trigeminal neuralgia".)

ANATOMY — The intermediate nerve of Wrisberg (the nervus intermedius) is a small sensory branch of the facial nerve (cranial nerve VII) carrying general visceral efferent, special visceral afferent (taste), and general somatic afferent fibers (figure 1) [5]. The cell bodies of the sensory afferents dwell in the geniculate ganglion, and their peripheral axons innervate the inner ear, the middle ear, the mastoid cells, the eustachian tube, and part of the pinna of the ear [5,6].

PATHOPHYSIOLOGY — There is no proven pathologic substrate for nervus intermedius neuralgia [6]. In addition, there is no indisputable evidence that the neuralgic pain originates in the geniculate ganglion or the nervus intermedius.

Some investigators believe that compression of the nerve by a blood vessel is an important mechanism [7,8], and relief of pain by vascular decompression of the intermediate nerve provides some support for this position [7]. However, there are multiple cranial nerve afferents in the ear [9], and otalgia in these cases could have resulted from a compromise to the nervus intermedius and/or other cranial nerves. In different surgical reports, section or decompression of a combination of cranial nerves V, VII, VIII, IX, X, and/or XI has been necessary to obtain relief [1,5]. Thus, the role of vascular compression in the pathogenesis of geniculate and other neuralgias is disputed [10].

EPIDEMIOLOGY — Nervus intermedius neuralgia is rare, and only limited data are available regarding the incidence, prevalence, and risk factors associated with this condition. Middle-aged women are predominantly affected, as found in a systematic review of the literature published in 2013 [11]. Of the identified 15 cases of surgically validated nervus intermedius neuralgia, women accounted for 14 (93 percent), and the median age at symptom onset was 41 years (range 16 to 47 years).

CLINICAL MANIFESTATIONS — The syndrome consists of brief (usually lasting seconds, rarely minutes), severe paroxysmal pain, felt within the depths of the ear, and sometimes is associated with a trigger-zone in the posterior wall of the ear canal. The pain can be sharp or burning, may involve the auricle, and sometimes radiates from the auditory canal to the parieto-occipital region or to trigeminal sensory zones [4,11]. Altered taste perception, such as a sense of bitter taste, can occur in some individuals, as can disorders of lacrimation or salivation [1,4,6].

The presence of an attack trigger (ie, auditory canal stimulation) was once considered a characteristic feature of nervus intermedius neuralgia. However, a systematic review found that a trigger was described in only 3 of 10 patients with available data [11].

DIAGNOSIS — The diagnosis of nervus intermedius neuralgia is made on clinical grounds and is based upon pain description. The diagnosis requires ruling out other neurologic and otolaryngologic causes of ear pain [5].

The diagnosis of classic nervus intermedius neuralgia, according to the International Classification of Headache Disorders 3rd edition (ICHD-3), requires fulfilling all of the following criteria [4]:

●Paroxysmal attacks of unilateral pain in the distribution of nervus intermedius

●Pain has all of the following characteristics:

•Lasting from a few seconds to minutes

•Severe in intensity

•Shooting, stabbing, or sharp in quality

•Precipitated by stimulation of a trigger area in the posterior wall of the auditory canal and/or periauricular region

●Not better accounted for by another ICHD-3 diagnosis

The condition is rare if one carefully adheres to these criteria. Although the ICHD-3 diagnostic criteria mandate the presence of a trigger area in the auditory canal, this is not always present [12].

Differential — The differential diagnosis for otalgia is broadly divided into primary (pathology within the ear such as infection, inflammation, trauma, or neoplasm) versus secondary (referred) causes [12]. Nerves referring pain to the ear include branches of cranial nerves V, VII, IX, and X, and upper cervical nerve roots (C2-C3) via the great auricular and lesser occipital nerves [12]. Pathology affecting any of these neural structures can potentially refer pain to the ear.

Some patients fitting ICHD-3 diagnostic criteria for nervus intermedius neuralgia [4] may have a variant of glossopharyngeal neuralgia with pain paroxysms restricted to the ear [11]. This is the main disorder in the differential diagnosis. In such cases, the typical pharyngeal pain of glossopharyngeal neuralgia may not occur until years later [1]. (See "Overview of craniofacial pain", section on 'Glossopharyngeal neuralgia'.)

In a few case reports, vascular compression of cranial nerve VII, the intermediate nerve, and cranial nerve VIII by a loop of the anterior inferior cerebellar artery was identified as the cause of intractable paroxysmal ear pain. One patient also had ipsilateral sensorineural hearing loss, tinnitus, and positional vertigo [7]; another had hemifacial spasm [8].

Secondary nervus intermedius neuropathy is most commonly caused by reactivation of latent varicella-zoster virus (ie, herpes zoster) within the geniculate ganglion, with subsequent spread of inflammation to nearby ganglia and cranial nerves, leading to ear pain, ipsilateral facial paresis, and vesicular eruption in the auditory canal and auricle (ie, the Ramsay Hunt syndrome). (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Ramsay Hunt syndrome (herpes zoster oticus)'.)

Evaluation — As noted above, it is necessary to rule out other neurologic, otolaryngologic, and infectious causes of ear pain in cases of suspected nervus intermedius neuralgia. We recommend a brain MRI (contrast-enhanced) and MRA for patients with suspected classic nervus intermedius neuralgia to rule out a structural lesion or vascular compression.

The workup requires a contrast-enhanced magnetic resonance imaging (MRI) of the brain, focusing on the internal auditory meatus. Brain MRI is useful for identifying structural brain lesions (eg, demyelinating lesions or a mass lesion in the cerebellopontine angle). Magnetic resonance angiography (MRA) is useful for demonstrating an ectatic blood vessel compressing the nerve. However, the sensitivity and specificity of these imaging studies for identifying a secondary cause of ear pain in patients with suspected nervus intermedius neuralgia and a normal neurologic examination is unknown.

Brain MRI, however, does not image all areas that can refer pain to the ear. Therefore, MRI of the face and soft tissues of the neck may be needed in some cases [12]. Urgent brain imaging is warranted if there are neurologic deficits.

TREATMENT — The rarity of nervus intermedius neuralgia has precluded accumulation of data that could guide therapy [5,6]. Pharmacologic treatment is based largely upon extrapolation from treatments that are effective for other cranial neuralgias, mainly trigeminal neuralgia. (See "Trigeminal neuralgia", section on 'Medical treatment'.)

Pharmacotherapy — As with trigeminal neuralgia, a trial of carbamazepine is reasonable for patients with nervus intermedius neuralgia. The usual starting dose of carbamazepine is 100 to 200 mg twice daily. The dose can be increased slowly over several weeks as needed for pain relief, with a typical maintenance dose of 600 to 1200 mg daily in divided doses.

Adverse effects of carbamazepine include drowsiness, dizziness, nausea, and vomiting; slow titration may minimize these effects. Carbamazepine-induced leukopenia is a potential adverse effect, but it is usually benign. Aplastic anemia is a rare side effect. The Stevens-Johnson syndrome and toxic epidermal necrolysis are additional rare complications, particularly during the first eight weeks of therapy. They are significantly more common (estimated incidence of 5 percent) among patients with the HLA-B*1502 allele. This allele occurs almost exclusively in patients of Asian ancestry, including South Asian Indians. Screening for this allele is recommended in patients of these ethnic groups prior to starting carbamazepine. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Genetic factors' and "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Carbamazepine'.)

For patients who do not tolerate or respond to carbamazepine, likely the best next alternative drugs are oxcarbazepine or baclofen. Other reasonable options are gabapentin, pregabalin, and phenytoin. Tricyclic antidepressants (eg, amitriptyline) are only occasionally effective.

Surgery — Neurosurgery is considered as a last resort when pharmacotherapy fails or when adverse effects of medications significantly reduce quality of life. However, there are limited data to guide operative techniques [13]. The opinion of an experienced neurosurgeon, familiar with the detailed anatomy of the nervus intermedius and its variants, and with intraoperative anatomic findings, should be obtained to choose the most appropriate intervention [13]. Alone, sectioning of the nervus intermedius is often ineffective [14].

●Most often, the procedure involves excision of the nervus intermedius and geniculate ganglion [15], with or without exploration and/or section of cranial nerves V, IX, and X [16]. The surgeon may elect to perform vascular decompression if a potential offending vessel is seen during exploration. One series of 64 patients who had excision of the nervus intermedius and geniculate ganglion reported "excellent" results in 63 patients, but outcomes were not objectively defined in this report [15]. Complications included a temporary partial facial paralysis in 11 patients (17 percent). In addition, permanent ipsilateral xerophthalmia is an expected outcome, due to sectioning of the greater petrosal nerve as part of the surgical approach to the geniculate ganglion.

●Microvascular decompression of cranial nerves V, IX, and X, with or without section of the nervus intermedius, is another option [17,18]. In a series of 10 patients with nervus intermedius neuralgia treated with microvascular decompression who had long-term (>12 months) follow-up, an "excellent" outcome was reported for three patients, and partial relief for six [19].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neuropathic pain".)

SUMMARY AND RECOMMENDATIONS

●Nervus intermedius neuralgia is a rare disorder characterized by brief paroxysms of pain felt deeply in the auditory canal. Middle aged women are predominantly affected. (See 'Introduction and definition' above and 'Epidemiology' above.)

●The symptoms of nervus intermedius neuralgia consist of episodes of brief (seconds to minutes), severe paroxysmal pain, felt in the depths of the ear, sometimes radiating to the parieto-occipital region or trigeminal sensory zones, and sometimes triggered by stimulation in the posterior wall of the ear canal. The pain can be sharp or burning. (See 'Clinical manifestations' above.)

●The diagnosis of nervus intermedius neuralgia is made on clinical grounds and is based upon pain description. The diagnosis requires ruling out other neurologic and otolaryngologic causes of ear pain. (See 'Diagnosis' above.)

●The differential diagnosis includes primary (pathology within the ear) and secondary (referred) causes of otalgia. Atypical presentations of glossopharyngeal neuralgia with pain paroxysms restricted to the ear may be difficult to distinguish from nervus intermedius neuralgia. Secondary nervus intermedius neuropathy is most commonly caused by herpes zoster. (See 'Differential' above.)

●For patients with suspected classic nervus intermedius neuralgia, we recommend a contrast-enhanced brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to rule out a structural lesion or vascular compression. Face MRI and neck soft tissue MRI may also be needed in some cases. (See 'Evaluation' above.)

●For patients with classic nervus intermedius neuralgia, we suggest initial treatment with carbamazepine (Grade 2C). Alternatives include oxcarbazepine, baclofen, gabapentin, pregabalin, and phenytoin. Neurosurgical treatment is an option if pharmacotherapy fails. (See 'Treatment' above.)