Continuing Education Activity

Trigeminal neuralgia is one of the most painful neurological conditions and is often described as a 'lightning bolt' stuck on the face or a stabbing sensation on the face. Indeed, such short-lasting paroxysms of pain occur multiple times throughout the day, debilitating the patient. This condition is almost always unilateral and can involve one or more divisions of the trigeminal nerve. This activity illustrates the evaluation and management of trigeminal neuralgia and highlights the role of the interprofessional team in evaluating, managing, and improving care for patients with this condition.

Objectives:

• Identify the etiology and epidemiology of trigeminal neuralgia.
• Outline the appropriate history, physical, and evaluation of trigeminal neuralgia.
• Review the treatment and management options available for trigeminal neuralgia.
• Describe interprofessional team strategies for improving care coordination and communication to improve outcomes in patients with trigeminal neuralgia.

Introduction

Trigeminal neuralgia (TN), also known as tic douloureux, is a chronic pain condition characterized by recurrent brief episodes of electric shock-like pains affecting the fifth cranial (trigeminal) nerve, which supplies the forehead, cheek, and lower jaw. This condition is almost always unilateral and can involve one or more divisions of the trigeminal nerve.[1] TN is a syndrome characterized by paroxysmal facial pain. The term “tic douloureux” was given by the French physician Nicolaus Andre in 1756 because of the facial spasms that can sometimes accompany severe pain attacks.

Etiology

The trigeminal nerve is the fifth cranial nerve. It is responsible for the sensory supply of the face and the motor and sensory supply to the muscles of mastication. The trigeminal nerve starts at the pons and divides into three branches[2]:

• Ophthalmic (V1): Supplies the eye, upper eyelid, and the forehead
• Maxillary (V2): Supplies lower eyelid, cheek, nostril, upper lip, and upper gum
• Mandibular (V3): Supplies the lower lip, lower gum, jaw, and the muscles of mastication

The trigeminal nerve starts at the pons. Most cases of trigeminal neuralgia are due to the compression of the trigeminal nerve root within a few millimeters of its entry into the pons. Between 80% and 90% of the cases of TN are caused by compression by an adjacent artery or a vein.[3] The blood vessel, which has been mostly implicated in about 75% to 80% of the cases, is the superior cerebellar artery. Other blood vessels that are known to cause TN include the anterior inferior cerebellar artery, the vertebral artery, and the petrosal vein.

Some of the other causes of nerve compression include meningioma, acoustic neuroma, epidermoid cyst, and rarely an arteriovenous malformation or a saccular aneurysm.

Multiple sclerosis is a risk factor for TN, and it is reported in about 2% to 4% of patients with TN. This is secondary to the demyelination of the trigeminal nerve nucleus by multiple sclerosis.[4]

Epidemiology

Trigeminal neuralgia affects 4 to 13 per 100000 people annually. Women are affected more compared to men. The male-to-female prevalence ratio ranges from 1 to 1.5 to 1 to 1.7. Most cases occur after age 50; some cases are seen in the second and third decades and are very rarely seen in children.[5] The lifetime prevalence in population-based studies was estimated to be about 0.16% to 0.3%.[6]

The development of trigeminal neuralgia in a young person should raise suspicion of multiple sclerosis. The prevalence of TN in patients with multiple sclerosis is between 1 and 6.3%. It is also reported that patients with hypertension have a slightly higher incidence of TN compared to the general population.

Pathophysiology

Most cases of trigeminal neuralgia are due to trigeminal nerve compression. It is believed that TN is related to nerve demyelination occurring around the site of compression. The mechanism of how demyelination leads to the symptoms of TN is not known. It is thought to be due to the ectopic impulse generation set up by the demyelinated lesion, thereby causing ephaptic transmission.[7] The ephaptic link between fibers involved in pain generation and fibers mediating light touch could account for the precipitation of shock-like pains in the facial trigger zone by light tactile stimulation.

A triggered episode followed by refractory periods and a single stimulus leading to painful sensations indicates the possible role of the central pain mechanism in TN. Altered grey matter in the sensory and motor cortex has also been described.[8]

Some theories describe demyelination secondary to vascular compression of the nerve root by tortuous or aberrant vessels. Radiologic and pathologic studies have demonstrated the proximity of the trigeminal nerve root to such vessels. The vessel mostly implicated is the superior cerebellar artery.[9] This hypothesis is further strengthened by the relief of symptoms following surgeries to separate the offending vessels from the nerve.

According to the bio-resonance hypothesis, when the vibration frequency of the trigeminal nerve and the surrounding structures come close to each other, the trigeminal nerve fibers are damaged, leading to abnormal transmission of impulse, thereby resulting in facial pain.[10]

Multiple other conditions like amyloid infiltration, bony compression, arteriovenous malformation, and small infarcts in the medulla and pons have been described to cause TN.

Classification

TN is divided into classic TN, secondary TN, and idiopathic TN in the International Classification of Headache Disorders, Third Edition (ICHD-3)[1]:

Classic TN: This includes TN related to vascular compression.

Secondary TN: This includes TN due to a tumor along the trigeminal nerve or TN due to an underlying disease like multiple sclerosis.

Idiopathic TN: This is when the cause is unknown. 

History and Physical

Considering the symptomatic aspect, trigeminal neuralgia can classify as[5]:

• Type 1 - Presence of paroxysmal pain alone
• Type 2 - Paroxysmal pain along with constant pain in the background

The pain in trigeminal neuralgia occurs in paroxysms and is usually maximal at or near onset. Sometimes, with severe pain, facial muscle spasms can be seen. Hence, TN is also known as 'tic douloureux.' 

The majority of the patients describe the pain as electric shock-like pain, lasting from one to several seconds. Pain in TN is typically unilateral. Occasionally, it is bilateral, but very rarely occurs simultaneously on both sides.[11] The pain episodes rarely occur during sleep.

V2 and V3 divisions of the trigeminal nerve are usually involved in the pain distribution.[1] When the V1 subdivision is involved, mild autonomic symptoms like lacrimation, rhinorrhea, and conjunctival injection can be seen. However, isolated V1 division involvement is very rare and is seen in less than 5% of patients with TN.[12] 

Trigger zones may be present in the distribution of the affected nerve. These are usually located near the midline. They have been mostly reported in the nasal and perioral regions. TN pain is triggered by lightly touching these zones.[13] Patients with TN are usually aware of these zones and avoid any stimulation of them. All patients with TN may not have trigger zones, but trigger zones are nearly pathognomonic for TN. 

Other triggers reported causing trigeminal neuralgia paroxysms include brushing teeth, shaving, washing the face, smoking, chewing, talking, grimacing, or exposure to cold air.[12]

In younger patients, who present with symptoms of TN, other neurological conditions like multiple sclerosis should merit consideration in the differentials. Such patients should be asked about other neurological symptoms like focal weakness, vision changes, dizziness, and ataxia. 

In patients with TN, the physical examination is generally normal. Hence, the physicians should perform a detailed physical examination of the head, neck, eyes, ears, teeth, mouth, and the temporomandibular joint to rule out other causes of facial pain. The finding of typical trigger zones is suggestive of TN. 

In patients with classic TN, the neurologic examination is normal. Hence, physical examination showing a sensory loss in trigeminal nerve distribution, loss of corneal reflex, or weakness in facial muscles should prompt the physician to consider secondary TN and other differentials. 

Several patients with TN complain of toothache and pain with brushing teeth. A detailed oral examination can help in differentiating the dental causes of pain from trigeminal neuralgia.

Evaluation

Trigeminal neuralgia is usually diagnosed based on the history and the description of the symptoms by the patients. For patients with clinically suspected TN, it is recommended to have neuroimaging studies to distinguish classic TN from secondary TN. MRI of the brain is preferred over CT, as the MRI helps in evaluating small adjacent lesions as well.

There are certain diagnostic criteria established by the ICHD-3, which can help in the diagnosis of TN. These criteria are as follows[1]:

A) Recurrent paroxysms of facial pain unilaterally in the distribution of trigeminal nerve and fulfilling criteria B and C.

B) Pain has the following characteristics:

• Pain lasting a fraction of a second to about 2 minutes
• Pain with severe intensity
• Electric-shock like or shooting pain with sharp quality

C) Innocuous stimuli precipitate the pain in the affected distribution

D) No alternative ICHD-3 diagnosis better explains the symptoms

The subtypes of TN are defined by ICHD-3 as follows[1]: 

• Classic TN: This is secondary to neuromuscular compression and fulfilling the criteria above. This requires demonstration of the compression on an MRI or during the surgery for neuromuscular compression, with associated morphological changes in the trigeminal nerve root. 
• Secondary TN: This is defined as TN secondary to an underlying disease. Some of the reported causes are multiple sclerosis, arteriovenous malformation, and cerebellopontine angle tumor. 
• Idiopathic TN: This is defined as TN with no abnormalities seen on MRI or electrophysiological tests. 

Neuroimaging studies like MRI Brain or CT Head can help in identifying causes like cerebellopontine angle tumor or multiple sclerosis, which can cause secondary TN. [14] Magnetic resonance imaging or high-resolution MRI can help in identifying vascular compression as the cause of classic TN.[15][16] A targeted MRI, which is a high-resolution MRI, can be performed with or without gadolinium contrast. This can give a detailed picture of the blood vessels and the brain. This is called FIESTA sequences in some MR machines. In these machines, sections as thin as 1 mm can be taken in a coronal plane without any skips in between the images. This way, the imaging of the entire course of the trigeminal nerve can be obtained, and the offending vessel causing compression can be identified. 

Hence, though TN is a clinical diagnosis, an MRI of the brain with and without contrast is recommended to rule out a structural brain lesion in all patients with clinically suspected TN. It is also important to note that patients less than 40 years of age, patients with bilateral symptoms, and with sensory loss on physical examination are at a higher risk of secondary trigeminal neuralgia. 

Treatment / Management

The management options for patients with trigeminal neuralgia depend on a variety of factors, including age, general health, disease severity, and the underlying cause. The decision should be taken after a thorough discussion with the patient and other doctors involved in the care of the patient. 

Pharmacologic Therapy

• The first-line treatment for patients with classic TN and idiopathic TN is pharmacologic therapy. The most commonly used medication is the anticonvulsant drug carbamazepine.[2] It is usually started at a low dose, and the dose is gradually increased until it controls the pain. It controls pain for most people in the early stages of the disease. However, in some patients, the effectiveness of carbamazepine decreases over time. Possible side effects of carbamazepine include drowsiness, dizziness, double vision, and nausea. In patients of Asian ancestry, before starting carbamazepine, testing for HLA-B*15:02 allele is recommended, as its presence increases the risk of development of toxic epidermal necrolysis or Stevens-Johnson syndrome.[17]
• Oxcarbazepine is a newer drug and is being increasingly used as first-line therapy for TN in patients who do not respond to or who cannot tolerate carbamazepine. Possible side effects include double vision and dizziness. It can also cause hyponatremia. It should also be avoided in patients with HLA-B*15:02 allele.
• Baclofen is a muscle relaxant that can be used to treat TN. Side effects include dizziness, sedation, and dyspepsia. 
• Other medications include lamotrigine, phenytoin, gabapentin, clonazepam, and valproic acid.
• Newer drugs like eslicarbazepine, an active metabolite of oxcarbazepine, and the new Nav1.7 blocker, vixotrigine, are being explored for pain relief in TN.[2]
• Patients with secondary TN also can respond well to pharmacotherapy. However, it is recommended to treat the underlying lesion or disease.

Botulinum Toxin Injections [18]

This can be beneficial for some patients, particularly the middle-aged and the elderly, who are refractory to medical therapy or who cannot tolerate medical therapy due to its side effects.[19]

Surgical Therapy

• Patients who are refractory to medical therapy can be considered for surgery.

• Microvascular decompression [20]: This is one of the most common procedures used to treat trigeminal neuralgia. This is beneficial for patients with TN, where compression of the nerve root is the cause. This involves craniotomy and posterior fossa exploration for identifying and moving the blood vessel that is compressing the trigeminal nerve. A soft cushion is then inserted between the nerve and the vessel to allow the nerve to recover, which eventually relieves the pain. In some patients, this procedure can result in sustained pain relief for greater than 10 years. Though this is the most effective procedure, it is also the most invasive one. Some of the complications associated with it are decreased hearing, cerebellar hematoma, CSF leaks, infarction, and facial weakness. It is believed to be the most effective long-term surgical treatment available currently for patients with TN.[21]

• Ablative procedures include rhizotomy with thermocoagulation, chemical injection, or mechanical balloon compression. These procedures involve damaging the trigeminal nerve root, thereby interrupting the pain transmission signals to the brain. Rhizotomy with thermocoagulation uses an electrode to apply heat to damage the nerve fibers. Chemical rhizotomy involves injecting the chemical glycerol into the trigeminal nerve, thereby damaging it. Balloon compression involves inserting a tiny balloon to the point of location of nerve fibers.[22][23] This balloon, on inflation, damages the nerve fibers. Some of the associated complications are postoperative dysesthesia, corneal numbness, sensory loss in trigeminal nerve distribution, and anesthesia dolorosa. 

• Radiosurgery: This procedure involves using radiosurgery instrumentation.[24][25][26] This is a non-invasive procedure wherein a highly concentrated dose of ionizing radiation is delivered to a precise target at the trigeminal nerve root. The radiation creates a lesion near the nerve root, thereby interrupting the pain signals from transmission to the brain. The formation of the lesion can be slow, and hence the pain relief using this procedure is delayed by up to several weeks or months. As this is one of the least invasive procedures, it can be repeated in patients who have a recurrence of pain. Some of the associated complications can be facial sensory loss and paresthesias. 

• Peripheral neurectomy and nerve block: The neurectomy can be performed on peripheral branches of the trigeminal nerve like the supraorbital, infraorbital, lingual, and the alveolar nerves.[27] This can be accomplished by alcohol injection, incision, cryotherapy, or radiofrequency lesioning. Peripheral neurectomy can be safe in elderly patients in remote and rural areas, where neurosurgical facilities are not readily available.[28] However, the evidence regarding these peripheral techniques for trigeminal neuralgia is inconclusive.

Differential Diagnosis

A good history and physical examination can help in differentiating trigeminal neuralgia from other similar conditions.

• Postherpetic neuralgia: This is secondary to acute Herpes zoster. This usually presents with a severe preceding rash. Often involves the first division of the trigeminal nerve, and the pain is usually continuous. TN pain is intermittent and lasts a few seconds.
• Dental pain: This is usually continuous and intraoral pain, which can be dull or throbbing. TN pain is usually sharp, intermittent, and electric-shock like. Also, abnormalities are found on oral examination if the pain is from a dental source.
• Short-lasting unilateral neuralgiform headache attacks (SUNA) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT): These present as sudden, brief attacks of unilateral pain in orbital, periorbital, and temporal regions. Ipsilateral autonomic symptoms also accompany these. 
• Trigeminal neuropathy: This condition presents with persistent pain and can be associated with sensory loss.
• Temporomandibular joint syndrome: This condition presents with persistent pain. Localized tenderness and jaw abnormalities can be demonstrated. 
• Glossopharyngeal neuralgia: Patients present with pain in the tongue, mouth, and throat. The pain is triggered by chewing, talking, and swallowing.

Prognosis

Trigeminal neuralgia is not a life-threatening condition. However, it can lead to lifelong pain and can be disabling. The course of TN is variable. Some patients may have episodes lasting weeks or months, followed by pain-free intervals. Some patients have persistent background facial pain concomitantly with TN. In some patients, the pain attacks worsen over time, with fewer and shorter pain-free intervals before they recur. Also, the medications might lose effectiveness over time. Correct diagnosis and proper management can be beneficial to the patients and leads to a good prognosis. 

Complications

• The pain in trigeminal neuralgia is so severe and debilitating that the patients can develop depression if not adequately treated.
• Patients with severe pain associated with facial twitches can become socially withdrawn due to embarrassment and fear of an impending attack.
• Patients treated with anticonvulsant drugs over the long term can have adverse drug effects.
• Microvascular decompression and percutaneous neurosurgical procedures can pose surgical risks. 
• Some patients permanently develop facial numbness on the affected side.
• Occasionally, patients develop corneal anesthesia and jaw weakness.
• Anesthesia dolorosa is seen in a few patients. It is an intractable facial dysesthesia, which can be more disabling than original TN.

Consultations

Although a primary care provider can do the diagnosis and the initial treatment of trigeminal neuralgia, referral to general neurology may be necessary to identify possible secondary causes like multiple sclerosis, arteriovenous malformations, and cerebellopontine tumors. Consultation with a neurosurgeon or a neurovascular surgeon is warranted for patients who are refractory to medical therapy to assess the necessity of microvascular decompression or other surgical procedures.

Deterrence and Patient Education

Timely diagnosis and management of trigeminal neuralgia are essential, as the pain is severe and can be debilitating and affect the quality of life. Patients should be informed about the condition. Patients should be educated about the course of this condition and the various therapeutic options available. Patients should be made aware of the risks of long term anticonvulsant therapy and also the risks associated with the surgical options for trigeminal neuralgia. This can help the patients in making an informed decision. 

Pearls and Other Issues

• Trigeminal neuralgia is a chronic pain condition that presents with unilateral facial pain.
• The pain in trigeminal neuralgia is usually described as a sharp, electric shock-like, stabbing, or lancinating pain in the distribution of one or more divisions of the trigeminal nerve. 
• The majority of the cases of trigeminal neuralgia are due to neurovascular compression.
• Although TN is a clinical diagnosis, neuroimaging study is recommended in all patients with clinically suspected TN to differentiate classic TN from secondary TN.
• Carbamazepine is a first-line medication in the treatment of trigeminal neuralgia.
• Microvascular decompression is one of the most effective surgical modalities for the treatment of trigeminal neuralgia.  

Enhancing Healthcare Team Outcomes

As trigeminal neuralgia is a clinical diagnosis, physicians need to be aware of the typical presentation of TN to reduce unnecessary imaging and investigations. TN is frequently misdiagnosed as toothache, thereby leading to root canal treatment and tooth extractions. Hence, physicians need to be aware of this condition. An interprofessional approach between the primary care physician, dentist, neurologist, anesthesiologist, and neurosurgeon is necessary to recognize and manage this condition. Otolaryngology and pain control nurses provide care to patients, inform them about their condition, and communicate with physicians. Since medical management is the typical first step, a pharmacist consult is in order to help guide agent selection, verify dosing, check for drug interactions, and counsel the patient on medication side effects. All patients with clinically suspected trigeminal neuralgia should undergo neuroimaging to look for secondary causes of TN. If a secondary etiology like multiple sclerosis is found, they should receive a prompt referral to a neurologist or a neurosurgeon for further management. These interprofessional strategies will improve patient outcomes in cases of trigeminal neuralgia. [Level 5]