Trigeminal Neuralgia in Emergency Medicine

Trigeminal neuralgia (TN), also known as tic douloureux, is a pain syndrome often recognizable by the patient's history alone. Trigeminal neuralgia is characterized by facial pain often accompanied by a brief facial spasm or tic. Pain distribution is unilateral and follows the sensory distribution of cranial nerve V, typically radiating to the maxillary (V2) or mandibular (V3) area, or rarely, the opthalmic (V3) area.[1]  At times, both distributions are affected. Physical examination will usually eliminate alternative diagnoses. Signs of dysfunction of other cranial neruves or other neurologic abnormality exclude the diagnosis of classic trigeminal neuralgia and suggest that pain may be secondary to a structural lesion.

The International Association for the Study of Pain (IASP) classifies TN into three categories.  Classical TN is described as vascular compression that causes anatomical changes in the trigeminal nerve root. Next, secondary TN is due to an underlying neurologic disease. Third, idiopathic TN, is diagnosed after all studies reveal no etiology or there is no apparent cause.[2]   

Classic trigeminal neuralgia includes all cases without established etiology after investigation, as well as those with potential microvascular compression of the fifth cranial nerve. In symptomatic trigeminal neuralgia, the pain syndrome is secondary to tumor, multiple sclerosis, or other structural abnormalities.[3]

Diagnosis

According to the International Classification of Headache Disorders (ICHD), specific crtieria have been developed to diagnose TN.[2]  They are as follows:

A. At least three attacks of unilateral facial pain fulfilling criteria B and C

B. Occurring in one or more divisions of the trigeminal nerve, with no radiation beyond the trigeminal distribution

C. Pain has at least three of the following four characteristics: 

1. recurring in paroxysmal attacks lasting from a fraction of a second to 2 min
2. severe intensity
3. electric shock-like, shooting, stabbing or sharp in quality
4. precipitated by innocuous stimuli to the affected side of the face

D. No clinically evident neurological deficit

E. No alternative diagnosis

The mechanism of pain production remains controversial. One theory suggests that peripheral injury or disease of the trigeminal nerve increases afferent firing in the nerve; failure of central inhibitory mechanisms may be involved as well. Pain is perceived when nociceptive neurons in a trigeminal nucleus involve thalamic relay neurons. An abnormal vascular course of the superior cerebellar artery is often cited as the cause, as well as other small arteries or veins compressing the facial nerve. In about 85% of cases, no lesion is identified, even after extensive investigations, and the etiology is labeled idiopathic (classic) by default.

Aneurysms, tumors, chronic meningeal inflammation, or other lesions may irritate trigeminal nerve roots along the pons, causing symptomatic trigeminal neuralgia. Uncommonly, an area of demyelination from multiple sclerosis may be the precipitant. Lesions of the entry zone of the trigeminal roots within the pons may cause a similar pain syndrome.

An area of demyelination is shown in the image below.

Infrequently, adjacent dental fillings composed of dissimilar metals may trigger attacks,[4] and an atypical case has been reported following tongue piercing. A case report of trigeminal neuralgia in a patient with spontaneous intracranial hypotension has been reported; both conditions resolved following surgical treatment of a cervical root sleeve dural defect.[5]

Frequency

Trigeminal neuralgia (TN) is uncommon, with an estimated prevalence of 155 cases per million persons. In patients over 75 years old it can occur in up to 1 per 1000 patients. Females are affected twice as often as males.[6]

Mortality/Morbidity

No mortality is associated with idiopathic trigeminal neuralgia (TN), although secondary depression is common if a chronic pain syndrome evolves. Depression can be severe enough that some patients have committeed suicide. Many patients suffer from decreased quality of life and imparirment of daily function.[1]  In rare cases, pain may be so frequent that oral nutrition is impaired.

In symptomatic or secondary trigeminal neuralgia, morbidity or mortality relates to the underlying cause of the pain syndrome.

Age

Development of trigeminal neuralgia in a young person suggests the possibility of multiple sclerosis.

Idiopathic trigeminal neuralgia typically occurs in patients in the fifth to eigth decade of life, but it may occur at any age.

Symptomatic or secondary trigeminal neuralgia tends to occur in younger patients.

History is the most important factor in the diagnosis of typical or classical trigeminal neuralgia (TN). Symptomatic trigeminal neuralgia secondary to intracranial processes may have a different history.

Nature of pain

Pain is brief and paroxysmal, but it may occur in volleys of multiple attacks.

Pain is stabbing or shock-like and is typically severe.

Distribution of pain

One or more branches of the trigeminal nerve (usually maxillary or mandibular in unilateral distribution) are involved.

Pain is unilateral in classical trigeminal neuralgia. Bilateral pain suggests symptomatic trigeminal neuralgia.[3]

Duration of pain is typically from a few seconds to 1–2 minutes. Pain may occur several times a day; patients typically experience no pain between episodes.

Trigger points

Various triggers may commonly precipitate a pain attack. Light touch or vibration or even talking can provoke attacks.

Activities such as shaving, face washing, or chewing often trigger an episode.

Stimuli as mild as a light breeze may provoke pain in some patients.

Pain provokes brief muscle spasm of the facial muscles, thus producing the tic.

There is a short refractory period after an attack where you cannot evoke a new attack with repeated stimulation to the same area.[1]

Physical examination findings should show no abnormality unless there is a prior or concommitant neurologic process. A normal neurologic examination is part of the definition of typical or classic trigeminal neuralgia (TN). Perform a careful examination of the cranial nerves, including the corneal reflex.

• Be alert to the presence of any abnormality on physical examination. Abnormality suggests that the pain syndrome is secondary to another process.

• Trigeminal sensory deficits suggest symptomatic trigeminal neuralgia.

• Remember that patients report pain following stimulation of a trigger point; thus, some patients may limit their examination for fear of stimulating these points.

Most patients' conditions are idiopathic, but compression of the trigeminal roots by tumors or vascular anomalies may cause similar pain (see Pathophysiology). The most common cause of nerve compression is from an artery pulsating against the nerve.

There are documented cases of development of TN following opthalmic surgery in rare cases.[7]

In the ED, providers may consider a CT scan of the brain or maxillofacial region to evaluate for alternative etiology such as dental or sinus disease. However, trigeminal neuralgia (TN) is a clinical diagnosis and the majority of patients with characteristic history and normal neurologic examination may be treated without further workup or imaging.

Some physicians recommend elective MRI with MRA for all patients to exclude an uncommon mass lesion or aberrant vessel compressing the nerve roots.

Consider an outpatient MRI to identify patients with structural causes or exclude other possible causes of facial pain.

In a published practice parameter, the American Academy of Neurology stated that because of inconsistency of studies, there was insufficient evidence to support or refute the usefulness of MRI or a specific MRI technique to identify vascular anomalies. The recommendation was that, for patients with TN, routine imaging may be considered to identify symptomatic TN, and this was graded as a Level C or possibly effective action.[8]

There is no strong evidence to support the use of evoked potentials.[1]

Studies have failed to yield a definitive guideline on the best treatment and escalation of treatment options for TN. The general consensus is to begin with medical therapy until it is ineffective or side effects of medication become prohibitive. For these patients it is reasonable to refer for surgical options without prolonged delay.[1]

Care in the ED is generally limited to correct identification of trigeminal neuralgia (TN), consideration of alternative diagnosis, pain relief, and coordination of follow-up care.

Because of the time-limited character of pain with typical trigeminal neuralgia, patients often do not present to the ED for pain medication.

In some patients, the typically episodic pain becomes constant or so frequent as to be debilitating. Infusion of phenytoin is reportedly successful in interrupting such episodes, but the value of this therapy is anecdotal.[9, 10]

Coordinate therapy for refractory pain of trigeminal neuralgia with the primary care physician or consultants.

Patients with a typical history and normal physical examination may be referred to their primary care physician for further care. Neurologic or neurosurgical consultations may be helpful, particularly if atypical features are present.

• Referral to a neurologist may be helpful if the diagnosis is in doubt or for medication management upon discharge.

• Comprehensive pain center follow-up care may be helpful. Pain specialists can inject local anesthetics that are used in the diagnosis and treatment of TN. These injections can provide relief from pain for a few months to years and help reduce the pain intensity and frequency in TN.

• Referral to a neurosurgeon may be indicated for patients whose conditions prove refractory to medical treatment. Percutaneous radiofrequency ablation of a portion of the trigeminal ganglion is commonly performed, as are anesthetic blocks of the trigeminal ganglion. Gamma knife radiosurgery is used at some centers.[11] Less commonly performed is decompression of the region of trigeminal root entry of impinging vascular structures. An MRI of a patient who has undergone gamma knife surgery is shown below.

  MRI with high resolution on the pons demonstrating the trigeminal nerve root. In this case, the patient with trigeminal neuralgia has undergone gamma-knife therapy, and the left-sided treated nerve (arrow) is enhanced by gadolinium.

First-line treatment for trigeminal neuralgia (TN) is medication, and if the medication fails or severe side effects develop, surgical treatment may be offered. Approximately half of patients will fail medical thearpy. Carbamazepine (CBZ) and oxcarbazepine (OXC) are considered first-line therapy. Compared to CBZ, OXC showed a similar efficacy in controlling pain but a greater tolerability and less drug interactions. Second-line therapy is with add-on drugs of lamotrigine or monotherapy with lamotrigine or baclofen.[1]

In the ED, an acute exacerbation may benefit from intravenous hydration, management of hyponatraemia, titration of drugs, and, in certain cases, lidocaine or fosphenytoin intravenous infusion, under cardiac monitoring.

Less invasive options for pain relief are currently being researched. These include repeated peripheral alcohol injections with a variable pain relief duration. Repeated injections have been noted to be more difficult due to fibrosis and were also associated with a decreased duration of pain relief. Average duration of symptomatic improvement was 11–15 months.[12]

Subcutaneous or intradermal Botulinum toxin-A (Botox) injections work by blocking acetylcholine release at the neuromuscular junction with resultant muscle relaxation through eventual deactivation of sodium channels in the CNS. Relief of symptoms was reported to be between 3 and 24 months. Adverse reactions reported included development of hemotoma and mild facial asymmetry.[13] One study reported that the effectiveness of the injection faded after 60 days.[1]

There is a novel sodium channel blocker injection currently being investiaged for use in TN.

Approximately half of trigeminal neuralgia (TN) patients will fail medical therapy and go on to require surgical management of their symptoms.

Neuromodulation is a treatment option when medication therapy has failed. Options include nerve stimulation at various locations along the trigeminal motor pathway including electrical Gasserian (trigeminal) ganglion stimulation, the peripheral nerve, as well as both non-invasive and invasive motor cortex stimulation.[1]  Destruction of the sensory component of the trigeminal nerve can also be done. Gamma knife radiosurgery can be an option for patients who are poor surgical candidates.

Microvascular decompression is an invasive surgical option to reduce vascular compression on the trigeminal nerve or ganglion. This procedure requires a craniotomy in the posterior fossa and risks include infarcts, hematomas, cerebral spinal fluid leaks, meningitis, hearing loss, and sensory loss.[1]  Pain relief following surgery can be immediate but can decrease over a time frame of years.

The goal of pharmacologic therapy is to reduce pain. Carbamazepine is regarded by most as the medical treatment of choice. Some advocate a trial of baclofen since it has fewer adverse effects. Oxcarbazepine may be better tolerated. The synergistic combination of carbamazepine and baclofen may provide relief from episodic pain though convincing clinical evidence is weak at best.

Other anticonvulsants including phenytoin, oxcarbazepine, clonazepam, lamotrigine, valproic acid, and gabapentin are reportedly beneficial in some patients; however, controlled trials have not been performed. The American Academy of Neurology published a practice parameter that concluded that carbamazepine is effective in controlling pain of patients with classic trigeminal neuralgia, and that oxcarbazepine is probably effective and may be better tolerated.[3] In another AAN guideline, baclofen, lamotrigine, and pimozide were rated as possibly effective. The practice parameter stated that there was insufficient evidence to support or refute efficacy of clonazepam, gabapentin, phenytoin, tizanidine, topical capsaicin, or valproate for pain control in patients with classic trigeminal neuralgia.[8] The writing group was unable to find sufficient evidence to support or refute the use of intravenous medications in acute exacerbations of trigeminal neuralgia.

A small randomized placebo-controlled trial using intraoral 8% lidocaine applied by the patient to the painful oral area suggested some benefit in patients with trigeminal neuralgia and severe intraoral pain.[14] More study is needed.

Class Summary

These agents may help control paroxysmal pain by limiting the aberrant transmission of nerve impulses.

Carbamazepine (Tegretol)

Anticonvulsant effective in the treatment of psychomotor and grand mal seizure. DOC for TN. May reduce polysynaptic responses and block post-tetanic potentiation.

Once patient responds to therapy, attempt to reduce dose to minimum effective level, or attempt to discontinue at 3-mo intervals.

Class Summary

These agents are useful in the treatment of TN, although not FDA-approved for this indication. They have CNS depressant properties as indicated by the production of sedation with somnolence, ataxia, and respiratory and cardiovascular depression. A recent review of nonepileptic drugs for trigeminal neuralgia concluded that there was insufficient evidence from randomized controlled trials to show significant benefit from nonantiepileptic drugs.[15]

Baclofen (Lioresal)

Most often used after therapy with carbamazepine has been initiated. Effects may be synergistic with those of carbamazepine. May induce hyperpolarization of afferent terminals and may inhibit both monosynaptic and polysynaptic reflexes at spinal level. As a structural analog of the inhibitory neurotransmitter GABA, may stimulate GABA-B receptor subtype.